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Elective postoperative radiation therapy in stages III and IV epidermoid carcinoma of the head and neck
Elective Postoperative Radiation Therapy in Stages III and IV Epidermoid Carcinoma of the Head and Neck
Bhadrasain Vikram, MD, New York, New York Elliot W. Strong, MD, New York, New York Jatin Shah, MD, New York, New York Ronald H. Spiro, MD, New York, New York
Surgical treatment of advanced carcinoma of the head and neck is followed by recurrences in the head and neck in an appreciable number of patients. Several reports from our institution have described the results of surgical treatment of patients with advanced but resectable carcinomas of the oral cavity, pharynx and larynx. Farr and Arthur [I] reported a recurrence rate of 38 to 73 percent at the primary site for various sites in the oral cavity and pharynx, considering early and advanced stages together. Spiro and Frazell [2] reported the results of surgical treatment in 222 patients with advanced carcinoma of the oral cavity and oropharynx who had both clinical and histologic evidence of metastatic cervical lymph nodes. Seventy-five percent of those patients failed treatment; the authors observed that recurrences in either the primary site or the dissected neck accounted for almost all of the failures. Shah and Tollefsen [3] studied patients with carcinoma of the supraglottic larynx and found that of those who presented with clinically or pathologically positive lymph nodes in the neck, only about 30 percent were long-term survivors; most of the others died of local or regional recurrence. Strong [4] reported that after radical neck dissection, recurrences in the dissected neck occurred in 36.5 percent of patients when metastases were present at one level and in 71.3 percent when multiple levels were involved. The overwhelming majority of recurrences (90 percent or greater) in all of these series appeared in the first 18 months after surgery. From the Department of Radiation Therapy and the Head and Neck %IIVIC~, of surgery, Memorial sloanxetterlng cancer center, New York, Ezaz Requests for reprints should be addressed to Shadrasain Vikram. MD, 1275 York Avenue, New York, New York 10021 Presented at the 26th Annual Meeting of the Society of Head and Neck Surgeons. San Francisco, California, May 14-17. 1980
560
The addition of low dose preoperative radiation therapy before radical neck dissection was found, in a prospective randomized study at Memorial Hospital, to improve the local control rate in the dissected neck [4-6]. Consequently, in an effort to improve local control, many patients with advanced disease were treated preoperatively with radiation therapy directed not only to the ipsilateral neck but to the primary site and the contralateral neck as well. In the mid-197Os, however, there was a gradual shift in interest away from preoperative and toward postoperative radiation therapy. It was felt that relatively higher doses of radiation would be necessary to improve the overall local control rate in these patients, and that such doses might be given with a smaller likelihood of complications postoperatively than preoperatively. More patients with advanced stages of disease were thereafter treated with postoperative irradiation, to the extent that at present only a few selected patients are being given planned preoperative irradiation. Therefore, the group of patients reported on herein, while representative, does not by any means include all of the patients with stage III and IV head and neck cancer treated at Memorial Hospital during the years mentioned herein, but only those referred for elective postoperative radiation therapy. The reasons for referral often included positive or suspect margins of resection, the presence of multiple metastastic lymph nodes in the pathologic specimen, extension of tumor to the soft tissues of the neck, and advanced stage of disease. While only a handful of patients treated with elective postoperative radiation therapy have been followed up for 5 years, over 100 have been followed up for at least 18 months, the period during which most local recurrences have been
The American Journal of Surgery
Postoperative
TABLE I
Tand N Stages Total
Stase
No
NI
N2
To Tr
T4
0 0 0 15 11
1 2 9 15 1
5 4 12 10 6
2 2 5 2 3
8 8 26 42 21
Total
26
28
37
14
105
T2 T3
N3
seen in the past. We therefore thought it worthwhile at this time to examine local control in these patients.
of surgery. No patient had gross residual or recurrent tumor when radiation therapy was started. Megavoltage radiation therapy with cobalt 60 was employed. The neck was irradiated in all patients and the primary site as well in 90 patients (86 percent). The portals generally encompassed the entire node-bearing area of the neck and the entire surgical scar. The primary site and the upper neck were usually irradiated by parallel opposing lateral portals, and a mid-plane dose ranging from 4,500 rads in 5 weeks to 6,000 rads in 6 weeks was delivered. Dose to the spinal cord was not allowed to exceed 4,500 rads, and an electron beam was employed to raise the dose in the shielded posterior part of the upper neck to the same level as the anterior part of the upper neck. The lower neck was treated through a single anterior portal and a given dose of 4,500 rads in 5 weeks to 5,500 rads in 5.5 weeks was delivered.
Material and Methods
Results
One hundred five patients with advanced (stages III and
The periods of follow-up at this writing range from 16 to 66 months. The results of treatment are summarized in Table II. Thirty-one of the 105 patients (29.5 percent) have had recurrence or metastases of cancer, and 12 (11.4 percent) have died from other causes. Of 93 determinate cases, 62 patients (66.6 percent) are alive free of cancer and 74 (79.5 percent) have remained free of cancer in the head and neck area. Patterns of recurrence: In 19 patients (18 percent) the cancer has recurred in the head and neck area: at the primary site in 10 (9.5 percent) and in the neck in 9 (8.5 percent). All of the recurrences at the primary site, except one, have occurred in patients whose cancers arose from the oral cavity or the oropharynx. No recurrences in the contralateral neck have been observed in 86 patients who underwent neck dissection on one side of the neck. One patient among 26 with stage NOnecks had recurrence in the neck; all of the other neck recurrences appeared in clinically positive, radically dissected necks. Twelve patients (11.6 percent) had distant metastases but no disease in the head and neck area. In four patients (3.8 percent) whose disease recurred in the head and neck area, distant metastases appeared
IV) [7] but resectable epidermoid carcinoma of the head and neck were treated by surgery and elective postoperative radiation therapy at Memorial Sloan-Kettering Cancer Center between July 1974 and December 1978. The primary site was the oral cavity in 37 patients (35 percent), the oropharynx in 15 (14.5 percent), the hypopharynx in 15 (14.5 percent), the larynx in 30 (28.5 percent) and unknown in 8 (7.5 percent). The T and N stages are shown in Table I. Forty-two patients (40 percent) had stage III disease and 63 (60 percent) stage IV disease. No patient had distant metastases initially, but 79 (75 percent) had clinically palpable metastatic lymph nodes in the neck. Six patients received one course of combination chemotherapy before surgery as part of a pilot study. The surgical procedures were radical in most instances, and radical neck dissection was performed in 94 patients (89.5 percent). Nine patients had bilateral neck dissections. Eighty-six patients (91.5 percent) undergoing neck dissection proved pathologically to have lymph nodes in the neck involved by cancer. In 35 patients (33.3 percent), tumor involved or approximated the resection margin microscopically. Radiation therapy was instituted after healing of the wounds was judged adequate by the operating surgeon. The interval from surgery to the start of radiation therapy varied from 3 to 16 weeks (median 6), but 93 of the patients (88.5 percent) started radiation therapy within 12 weeks
TABLE II
Results of Treatment
All Results’ Recurrence in head and neck Distant metastases only Alive and free of disease Total no. of patients l
Radiation in Head and Neck Cancer
No 19 12 61
Larynx
Primary Sates Oral Cavity and Oropharynx No. %
Hypopharynx No %
%
No
%
18 11.5 58
2 2 25
6.5 6.5 83.5
14 7 21
27 13 5 40
3 3 8
30
.
52
. .
15
105
20 20 54.5
.
Unknown No. % 0 0 7
0 0 87.5
8
...
Median follow-up 30 months (range 16 to 65)
Volume 140, October 1980
581
Vikram
et al
I
00
1
12.00
I
21.00
I
36.00
40.00
MONTHS FROM DRTE CIF SURGERY
simultaneously or subsequently. Figure 1 shows the proportion of patients who have had no local recurrence. The patients who had stage Noor Ni necks had fewer recurrences in the head and neck area and fewer distant metastases than the patients who presented with stage Ns or Ns metastatic disease in the neck (Table III). Interval from surgery to the start of radiation therapy: Fifty-four patients started radiation therapy 6 weeks or less after surgery, while in 51 patients radiation therapy was delayed beyond that period. Only 3 patients (5.6 percent) in the former group have had recurrence in the head and neck area, while 16 in the latter group (31.4 percent) have had recurrence (p
I
60.00
1
72.00
Figure 1. Proportion of patients remaining free of recurrence in the head and neck (Kaplan-Meler method).
disease at this writing, compared with 23 of 51(45.1 percent) of those in whom radiation was delayed longer. Could the foregoing observations be explained by the fact that the patients whose radiation therapy was delayed had more advanced cancer to start with? To address this question, a separate analysis was made of those 94 patients who underwent radical neck dissection and in whom, therefore, an accurate assessment of the extent of nodal involvement was available. It has been reported previously that the extent of nodal involvement in the neck has a tremendous effect on the likelihood of local control [4]. As indicated in Table IV, recurrences in the head and neck occurred less often when radiation therapy was initiated earlier, regardless of the pathologic status of the nodes. Comments
TABLE III
Recurrences and Metastases According to Clinical Stage Distant
Clinical Stage of Neck Disease
No NI N2 N3
582
No. of Patients 26 27 37 15
Recurrence in Head and Neck No. % 3 3 10 3
11.5 11 27 20
MetataseS
Only No. 96 0 2 6 2
0 7 21.5 13.5
While the present series is not strictly comparable to any of those mentioned earlier, all of the patients had advanced cancer, that is, clinically palpable metastatic lymph nodes or a Ts or T4 primary. Seventy-five percent had palpable metastatic nodes and 82 percent had pathologically proven metastatic lymph nodes. Based on prior experience, one would expect 50 to 75 percent of these patients to have a relapse in the head and neck region within the 1st
The Amrkan
Journal of Surgery
Postoperative
TABLE IV
Radiation in Head and Neck Cancer
Recurrences in the Head and Neck
Pathologic Status of the Neck
Delay up to 6 Weeks No %
Delay Over 6 Weeks % No.
Total No.
%
Nodes negatwe Nodes positive at one level Nodes positive at multiple levels
o/5 O/l8 2125
0 0 8
013 3111 12132
0 27 37
O/8 3129 14157
0 10.5 24.5
Total
2148
4
15146
32.5
17194
18
year and a half. That only 18 percent in this series have done so suggests an appreciable improvement in local control as a result of the addition of elective radiation therapy. The shape of the curve in Figure 1 is encouraging because it suggests that it is unlikely that many more local recurrences will be seen, even though the median follow-up period is only 2.5 years. It remains to be seen whether improvement in survival occurs as a result of improved local control. Already, several patients have died from distant metastases, new primary cancers (especially cancers of the esophagus and the lungs) and causes other than malignant disease. However, more of our patients have had recurrences in the head and neck area (19 patients) than have had distant metastases alone (12 patients) or new primary cancers (12 patients) or have died from other causes (6 patients). Local recurrence has thus remained the single greatest cause of morbidity and mortality for these patients. What then might one consider in an attempt to further decrease the likelihood of local recurrence? The data indicate that delay in the start of radiation therapy beyond 6 weeks decreased the likelihood of local control. Every effort should therefore be made to start irradiation as soon as possible after surgery. While delay might be due to unavoidable reasons in some cases, in others the likelihood of delay could be reduced by the elimination of unnecessarily extensive surgery or by careful selection of the reconstructive procedure. For instance, no recurrences were seen in this series in clinically negative contralateral necks; therefore elective neck dissections on clinically negative contralateral necks, when postoperative irradiation is planned, would not only be unlikely to increase the control rate, but might prove counterproductive by increasing the likelihood of delay in the start of radiotherapy. The keys to optimal utilization of this treatment scheme appear to be good communication between the specialists caring for the patient and minimal delay. Another possible solution is increasing the dose of radiation delivered. While a dose of about 5,000 rads in 5 weeks was usually mentioned in earlier reports on elective postoperative radiation therapy in head
Volume 140. October 1980
and neck cancer, recent reports indicate that some workers are now using doses of 6,000 rads and even 7,000 rads in some settings [8-JO]. Whether these higher doses will produce the desired increase in local control remains to be proven. It might well turn out that there is no single optimal dose level for all patients. As our experience with this method of treatment increases, we should be able to identify better those patients who might benefit from dose escalation. For instance, since we have observed recurrences at the primary site almost exclusively in the oral cavity and the oropharynx, it might be reasonable to irradiate these primary sites to a higher dose level. Also, when for whatever reason delay is unavoidable before radiation therapy can be instituted, a higher dose might be desirable since it is quite possible that the tumor cell burden to contend with is greater. This may be because residual microscopic cells have continued to multiply longer, or possibly because the proportion of hypoxic cells is higher (due to progressive fibrosis, entrapment and resultant decreased oxygenation of cells in the surgical field). Either way, a higher dose might be necessary for local control. However, higher doses could also result in an increased rate of complications [9]. To date we have seen few serious complications associated with the use of elective postoperative radiation therapy, but as our indications for the use of this treatment modality are expanding we must consider the possible adverse consequences, particularly when radiation is given after procedures such as partial laryngopharyngectomy or with reconstructive procedures in the mouth or pharynx. Results must be scrutinized carefully for their impact on the likelihood of tumor control as well as on morbidity. The minimum ports for elective postoperative radiation should be those which would have been employed had surgery not been performed. This means liberal coverage of the primary site and usually of the entire node-bearing area of the neck. These minimum ports frequently must be extended in light of the operative and pathologic findings to adequately irradiate any areas of special concern and the surgical scars. Small field radiation probably has no
563
Vikram
et al
place except for the delivery of booster doses. Due to alterations of anatomic configurations after surgery, tissue compensators often are required, and electron beams can be valuable in decreasing morbidity. Although some radiotherapists might consider postoperative radiation therapy to be like working in a vacuum, because of the absence of any tangible tumor to irradiate, in fact it often is a challenging task requiring considerable ingenuity. In conclusion, our experience so far indicates that elective postoperative radiation therapy has improved the local control rate in patients with advanced head and neck cancer, but that it is most effective when started within 6 weeks after surgery. Longer follow-up is necessary to determine whether survival will also be improved. Summary One hundred five patients with advanced (American Joint Committee stages III and IV) but resectable epidermoid carcinoma of the head and neck were treated with radical surgery and elective postoperative radiation therapy. Follow-up periods range from 16 to 66 months. Nineteen patients (18 percent) have had recurrence in the head and neck area. This is better than our past experience with surgical treatment alone in advanced head and neck cancer, in which 50 to 75 percent of patients had local recurrence within the 1st 18 months. When radiation therapy was started no later than 6 weeks after surgery, only 3 of 54 patients (5.5 percent) had local recurrence, but when there was a longer delay 16 of 51
patients (31.5 percent) had recurrence. These results suggest that elective postoperative radiation therapy improves local control in patients with advanced head and neck cancer, but that it should be delivered soon after surgery for maximum effectiveness. Acknowledgment: statistical analysis.
We thank David Braun, PhD, for
References 1 Farr HW, Arthur K. Epidermoid carcinoma of the mouth and pharynx, 1960-1964. J Laryngol Ctol 1972;86:243-53. 2. Spiro RH, Frazel! EL. Evaluation of radical surgical treatment of advanced cancer of the mouth. Am J Surg 1968,116: 571-7. 3. Shah JP, Tollefsen HR. Epidermoid carcinoma of the supraglottic larynx Role of neck dissection in Initial surgical treatment. Am J Surg 1974;128:494-9. 4. Strong EW. Preoperative radiation and neck dissection. Surg Clin North Am 1969;49:271-6. 5. Henschke UK, Frazell EL, Hllaris BS, Nickson JJ, Tollefsen HR, Strong EW. Local recurrences after radical neck dissection with and without preoperative x-ray therapy. Radiology 1964;82:331-2 6. Strong EW, liens&e UK, Nickson JJ, Frazell EL, Tollefsen RR, Hllarii BS. Preoperative x-ray therapy as an adjunct to radical neck dissection. Cancer 1966;19:1509-16. 7. American Joint Committee for Cancer Staging and End Results Reporting: Manual for staging of cancer. Chicago: 1978. 8. Fletcher GH. Textbook of radiotherapy. 2nd ed. Philadelphia: Lea 8 Febiger. 1973:275. 9. Marcus RB, Million RR, Cassissi NJ. Postoperative irradiation for squamous cell carcinomas of the head and neck: analysts of time-dose factors related to control above the clavicles. Int J Radiat Oncol Biol Phys 1979;5:1943-9. 10 Vandenbrouck C. Sancho H, LeFur R, Richard JM, Cachin Y. Results of a randomized clinical trial of preoperative irradiation versus post-operative in treatment of tumors of the hypopharynx. Cancer 1977;39:1445-9.
End of the papers of the Society of Head and Neck Surgeons
504
The American Journal of Surgery
Bhadrasain Vikram, MD, New York, New York Elliot W. Strong, MD, New York, New York Jatin Shah, MD, New York, New York Ronald H. Spiro, MD, New York, New York
Surgical treatment of advanced carcinoma of the head and neck is followed by recurrences in the head and neck in an appreciable number of patients. Several reports from our institution have described the results of surgical treatment of patients with advanced but resectable carcinomas of the oral cavity, pharynx and larynx. Farr and Arthur [I] reported a recurrence rate of 38 to 73 percent at the primary site for various sites in the oral cavity and pharynx, considering early and advanced stages together. Spiro and Frazell [2] reported the results of surgical treatment in 222 patients with advanced carcinoma of the oral cavity and oropharynx who had both clinical and histologic evidence of metastatic cervical lymph nodes. Seventy-five percent of those patients failed treatment; the authors observed that recurrences in either the primary site or the dissected neck accounted for almost all of the failures. Shah and Tollefsen [3] studied patients with carcinoma of the supraglottic larynx and found that of those who presented with clinically or pathologically positive lymph nodes in the neck, only about 30 percent were long-term survivors; most of the others died of local or regional recurrence. Strong [4] reported that after radical neck dissection, recurrences in the dissected neck occurred in 36.5 percent of patients when metastases were present at one level and in 71.3 percent when multiple levels were involved. The overwhelming majority of recurrences (90 percent or greater) in all of these series appeared in the first 18 months after surgery. From the Department of Radiation Therapy and the Head and Neck %IIVIC~, of surgery, Memorial sloanxetterlng cancer center, New York, Ezaz Requests for reprints should be addressed to Shadrasain Vikram. MD, 1275 York Avenue, New York, New York 10021 Presented at the 26th Annual Meeting of the Society of Head and Neck Surgeons. San Francisco, California, May 14-17. 1980
560
The addition of low dose preoperative radiation therapy before radical neck dissection was found, in a prospective randomized study at Memorial Hospital, to improve the local control rate in the dissected neck [4-6]. Consequently, in an effort to improve local control, many patients with advanced disease were treated preoperatively with radiation therapy directed not only to the ipsilateral neck but to the primary site and the contralateral neck as well. In the mid-197Os, however, there was a gradual shift in interest away from preoperative and toward postoperative radiation therapy. It was felt that relatively higher doses of radiation would be necessary to improve the overall local control rate in these patients, and that such doses might be given with a smaller likelihood of complications postoperatively than preoperatively. More patients with advanced stages of disease were thereafter treated with postoperative irradiation, to the extent that at present only a few selected patients are being given planned preoperative irradiation. Therefore, the group of patients reported on herein, while representative, does not by any means include all of the patients with stage III and IV head and neck cancer treated at Memorial Hospital during the years mentioned herein, but only those referred for elective postoperative radiation therapy. The reasons for referral often included positive or suspect margins of resection, the presence of multiple metastastic lymph nodes in the pathologic specimen, extension of tumor to the soft tissues of the neck, and advanced stage of disease. While only a handful of patients treated with elective postoperative radiation therapy have been followed up for 5 years, over 100 have been followed up for at least 18 months, the period during which most local recurrences have been
The American Journal of Surgery
Postoperative
TABLE I
Tand N Stages Total
Stase
No
NI
N2
To Tr
T4
0 0 0 15 11
1 2 9 15 1
5 4 12 10 6
2 2 5 2 3
8 8 26 42 21
Total
26
28
37
14
105
T2 T3
N3
seen in the past. We therefore thought it worthwhile at this time to examine local control in these patients.
of surgery. No patient had gross residual or recurrent tumor when radiation therapy was started. Megavoltage radiation therapy with cobalt 60 was employed. The neck was irradiated in all patients and the primary site as well in 90 patients (86 percent). The portals generally encompassed the entire node-bearing area of the neck and the entire surgical scar. The primary site and the upper neck were usually irradiated by parallel opposing lateral portals, and a mid-plane dose ranging from 4,500 rads in 5 weeks to 6,000 rads in 6 weeks was delivered. Dose to the spinal cord was not allowed to exceed 4,500 rads, and an electron beam was employed to raise the dose in the shielded posterior part of the upper neck to the same level as the anterior part of the upper neck. The lower neck was treated through a single anterior portal and a given dose of 4,500 rads in 5 weeks to 5,500 rads in 5.5 weeks was delivered.
Material and Methods
Results
One hundred five patients with advanced (stages III and
The periods of follow-up at this writing range from 16 to 66 months. The results of treatment are summarized in Table II. Thirty-one of the 105 patients (29.5 percent) have had recurrence or metastases of cancer, and 12 (11.4 percent) have died from other causes. Of 93 determinate cases, 62 patients (66.6 percent) are alive free of cancer and 74 (79.5 percent) have remained free of cancer in the head and neck area. Patterns of recurrence: In 19 patients (18 percent) the cancer has recurred in the head and neck area: at the primary site in 10 (9.5 percent) and in the neck in 9 (8.5 percent). All of the recurrences at the primary site, except one, have occurred in patients whose cancers arose from the oral cavity or the oropharynx. No recurrences in the contralateral neck have been observed in 86 patients who underwent neck dissection on one side of the neck. One patient among 26 with stage NOnecks had recurrence in the neck; all of the other neck recurrences appeared in clinically positive, radically dissected necks. Twelve patients (11.6 percent) had distant metastases but no disease in the head and neck area. In four patients (3.8 percent) whose disease recurred in the head and neck area, distant metastases appeared
IV) [7] but resectable epidermoid carcinoma of the head and neck were treated by surgery and elective postoperative radiation therapy at Memorial Sloan-Kettering Cancer Center between July 1974 and December 1978. The primary site was the oral cavity in 37 patients (35 percent), the oropharynx in 15 (14.5 percent), the hypopharynx in 15 (14.5 percent), the larynx in 30 (28.5 percent) and unknown in 8 (7.5 percent). The T and N stages are shown in Table I. Forty-two patients (40 percent) had stage III disease and 63 (60 percent) stage IV disease. No patient had distant metastases initially, but 79 (75 percent) had clinically palpable metastatic lymph nodes in the neck. Six patients received one course of combination chemotherapy before surgery as part of a pilot study. The surgical procedures were radical in most instances, and radical neck dissection was performed in 94 patients (89.5 percent). Nine patients had bilateral neck dissections. Eighty-six patients (91.5 percent) undergoing neck dissection proved pathologically to have lymph nodes in the neck involved by cancer. In 35 patients (33.3 percent), tumor involved or approximated the resection margin microscopically. Radiation therapy was instituted after healing of the wounds was judged adequate by the operating surgeon. The interval from surgery to the start of radiation therapy varied from 3 to 16 weeks (median 6), but 93 of the patients (88.5 percent) started radiation therapy within 12 weeks
TABLE II
Results of Treatment
All Results’ Recurrence in head and neck Distant metastases only Alive and free of disease Total no. of patients l
Radiation in Head and Neck Cancer
No 19 12 61
Larynx
Primary Sates Oral Cavity and Oropharynx No. %
Hypopharynx No %
%
No
%
18 11.5 58
2 2 25
6.5 6.5 83.5
14 7 21
27 13 5 40
3 3 8
30
.
52
. .
15
105
20 20 54.5
.
Unknown No. % 0 0 7
0 0 87.5
8
...
Median follow-up 30 months (range 16 to 65)
Volume 140, October 1980
581
Vikram
et al
I
00
1
12.00
I
21.00
I
36.00
40.00
MONTHS FROM DRTE CIF SURGERY
simultaneously or subsequently. Figure 1 shows the proportion of patients who have had no local recurrence. The patients who had stage Noor Ni necks had fewer recurrences in the head and neck area and fewer distant metastases than the patients who presented with stage Ns or Ns metastatic disease in the neck (Table III). Interval from surgery to the start of radiation therapy: Fifty-four patients started radiation therapy 6 weeks or less after surgery, while in 51 patients radiation therapy was delayed beyond that period. Only 3 patients (5.6 percent) in the former group have had recurrence in the head and neck area, while 16 in the latter group (31.4 percent) have had recurrence (p
I
60.00
1
72.00
Figure 1. Proportion of patients remaining free of recurrence in the head and neck (Kaplan-Meler method).
disease at this writing, compared with 23 of 51(45.1 percent) of those in whom radiation was delayed longer. Could the foregoing observations be explained by the fact that the patients whose radiation therapy was delayed had more advanced cancer to start with? To address this question, a separate analysis was made of those 94 patients who underwent radical neck dissection and in whom, therefore, an accurate assessment of the extent of nodal involvement was available. It has been reported previously that the extent of nodal involvement in the neck has a tremendous effect on the likelihood of local control [4]. As indicated in Table IV, recurrences in the head and neck occurred less often when radiation therapy was initiated earlier, regardless of the pathologic status of the nodes. Comments
TABLE III
Recurrences and Metastases According to Clinical Stage Distant
Clinical Stage of Neck Disease
No NI N2 N3
582
No. of Patients 26 27 37 15
Recurrence in Head and Neck No. % 3 3 10 3
11.5 11 27 20
MetataseS
Only No. 96 0 2 6 2
0 7 21.5 13.5
While the present series is not strictly comparable to any of those mentioned earlier, all of the patients had advanced cancer, that is, clinically palpable metastatic lymph nodes or a Ts or T4 primary. Seventy-five percent had palpable metastatic nodes and 82 percent had pathologically proven metastatic lymph nodes. Based on prior experience, one would expect 50 to 75 percent of these patients to have a relapse in the head and neck region within the 1st
The Amrkan
Journal of Surgery
Postoperative
TABLE IV
Radiation in Head and Neck Cancer
Recurrences in the Head and Neck
Pathologic Status of the Neck
Delay up to 6 Weeks No %
Delay Over 6 Weeks % No.
Total No.
%
Nodes negatwe Nodes positive at one level Nodes positive at multiple levels
o/5 O/l8 2125
0 0 8
013 3111 12132
0 27 37
O/8 3129 14157
0 10.5 24.5
Total
2148
4
15146
32.5
17194
18
year and a half. That only 18 percent in this series have done so suggests an appreciable improvement in local control as a result of the addition of elective radiation therapy. The shape of the curve in Figure 1 is encouraging because it suggests that it is unlikely that many more local recurrences will be seen, even though the median follow-up period is only 2.5 years. It remains to be seen whether improvement in survival occurs as a result of improved local control. Already, several patients have died from distant metastases, new primary cancers (especially cancers of the esophagus and the lungs) and causes other than malignant disease. However, more of our patients have had recurrences in the head and neck area (19 patients) than have had distant metastases alone (12 patients) or new primary cancers (12 patients) or have died from other causes (6 patients). Local recurrence has thus remained the single greatest cause of morbidity and mortality for these patients. What then might one consider in an attempt to further decrease the likelihood of local recurrence? The data indicate that delay in the start of radiation therapy beyond 6 weeks decreased the likelihood of local control. Every effort should therefore be made to start irradiation as soon as possible after surgery. While delay might be due to unavoidable reasons in some cases, in others the likelihood of delay could be reduced by the elimination of unnecessarily extensive surgery or by careful selection of the reconstructive procedure. For instance, no recurrences were seen in this series in clinically negative contralateral necks; therefore elective neck dissections on clinically negative contralateral necks, when postoperative irradiation is planned, would not only be unlikely to increase the control rate, but might prove counterproductive by increasing the likelihood of delay in the start of radiotherapy. The keys to optimal utilization of this treatment scheme appear to be good communication between the specialists caring for the patient and minimal delay. Another possible solution is increasing the dose of radiation delivered. While a dose of about 5,000 rads in 5 weeks was usually mentioned in earlier reports on elective postoperative radiation therapy in head
Volume 140. October 1980
and neck cancer, recent reports indicate that some workers are now using doses of 6,000 rads and even 7,000 rads in some settings [8-JO]. Whether these higher doses will produce the desired increase in local control remains to be proven. It might well turn out that there is no single optimal dose level for all patients. As our experience with this method of treatment increases, we should be able to identify better those patients who might benefit from dose escalation. For instance, since we have observed recurrences at the primary site almost exclusively in the oral cavity and the oropharynx, it might be reasonable to irradiate these primary sites to a higher dose level. Also, when for whatever reason delay is unavoidable before radiation therapy can be instituted, a higher dose might be desirable since it is quite possible that the tumor cell burden to contend with is greater. This may be because residual microscopic cells have continued to multiply longer, or possibly because the proportion of hypoxic cells is higher (due to progressive fibrosis, entrapment and resultant decreased oxygenation of cells in the surgical field). Either way, a higher dose might be necessary for local control. However, higher doses could also result in an increased rate of complications [9]. To date we have seen few serious complications associated with the use of elective postoperative radiation therapy, but as our indications for the use of this treatment modality are expanding we must consider the possible adverse consequences, particularly when radiation is given after procedures such as partial laryngopharyngectomy or with reconstructive procedures in the mouth or pharynx. Results must be scrutinized carefully for their impact on the likelihood of tumor control as well as on morbidity. The minimum ports for elective postoperative radiation should be those which would have been employed had surgery not been performed. This means liberal coverage of the primary site and usually of the entire node-bearing area of the neck. These minimum ports frequently must be extended in light of the operative and pathologic findings to adequately irradiate any areas of special concern and the surgical scars. Small field radiation probably has no
563
Vikram
et al
place except for the delivery of booster doses. Due to alterations of anatomic configurations after surgery, tissue compensators often are required, and electron beams can be valuable in decreasing morbidity. Although some radiotherapists might consider postoperative radiation therapy to be like working in a vacuum, because of the absence of any tangible tumor to irradiate, in fact it often is a challenging task requiring considerable ingenuity. In conclusion, our experience so far indicates that elective postoperative radiation therapy has improved the local control rate in patients with advanced head and neck cancer, but that it is most effective when started within 6 weeks after surgery. Longer follow-up is necessary to determine whether survival will also be improved. Summary One hundred five patients with advanced (American Joint Committee stages III and IV) but resectable epidermoid carcinoma of the head and neck were treated with radical surgery and elective postoperative radiation therapy. Follow-up periods range from 16 to 66 months. Nineteen patients (18 percent) have had recurrence in the head and neck area. This is better than our past experience with surgical treatment alone in advanced head and neck cancer, in which 50 to 75 percent of patients had local recurrence within the 1st 18 months. When radiation therapy was started no later than 6 weeks after surgery, only 3 of 54 patients (5.5 percent) had local recurrence, but when there was a longer delay 16 of 51
patients (31.5 percent) had recurrence. These results suggest that elective postoperative radiation therapy improves local control in patients with advanced head and neck cancer, but that it should be delivered soon after surgery for maximum effectiveness. Acknowledgment: statistical analysis.
We thank David Braun, PhD, for
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End of the papers of the Society of Head and Neck Surgeons
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The American Journal of Surgery