Ding-Jen Lee, MD, PhD •¿ Fishel Z. Liberman, MD, PhD •¿ Robert I. Park, MD •¿ Eva S. Zinreich, MD
Intraoperative 1-125 Seed Implantation for Extensive Recurrent Head and Neck Carcinomas' From 1978 to 1988, 41 patients with extensive recurrent carcinomas of the head and neck were treated with surgical resection plus intraopera tive iodine-125 seed implantation. Surgery
was performed
to resect
the
tumors and to expose the tumor beds for implantation. 1-125 seeds were implanted intraoperatively, with a spacing of 0.75-1 cm between adjacent seeds, either into the soft tissue in the tumor bed or onto small patches of gelatin sponges to cover the bone, nerve, or blood yes sel involved with disease. Recon structive flaps were used in 18 pa tients. The average 1-125 dose deliv ered by the implanted seeds was 8,263 cGy. The determinate 5-year actuarial survival rate for the entire group was 40%. The 5-year local dis ease control rate was 44%. Major complications were transient wound infection (32%), flap necrosis (24%), fistula formation (10%), and carotid blowout (5%). These results indicate that surgical resection plus 1-125 seed implantation provides a poten tially curative treatment for patients with extensive recurrent head and neck carcinomas that would be con sidered traditionally unresectable and that would be treated only with palliative therapy. Index terms: 28.37, 20.452,
Head and neck neoplasms, 20.454 •¿ Radionuclides,
tic, 20.452 •¿ Therapeutic
radiology,
therapeu
20.452
T
HE management
of recurrent
cal resection
head and neck carcinoma is a problem often faced by radiation on cologists and head and neck sum geons. Such tumors frequently in
volve deep neck structures
or the
covery
of radionuclides
themselves.
Radium-226, radon-222, inidiurn-192, and iodine-125 are just some of the radioactive sources that have been used in interstitial
radiation
The use of radionuclides advantage of delivering
therapy.
offers the a high dose
of radiation
to a localized
area while
minimizing
the dose to surrounding
tissue (1—3).
In patients with extensive recur rent head and neck carcinomas,
sun
vival rates remain poor, and the ma jon cause of death
is still local disease.
Surgical resection of the bulk of the disease
accompanied
Radiation
Oncology
(D.J.L., F.Z.L., E.S.Z.) and the Department of
panendoscopies,
under
biopsies,
and
CT and/or MR imaging. All of these cases
high-dose, localized radiation to the tumor-bearing area would achieve
Hopkins
Hospital
of the use of
implantation
MATERIALS
carcinoma in two patients, and one case
each of malignant melanoma and malig nant
mixed
tumor.
The original
stages
of
cancer were stage I in two cases (5%), stage II in seven (17%), stage III in 11 (27%), and stage IV in 21 (51%). However, the original stage did not reflect the ad
vanced nature of recurrence
in these pa
tients. All patients, except those whose original tumor was in the nasopharynx, initially underwent surgical resection. Thirty-eight (93%) received a course of
external-beam
radiation therapy, with a
median dose of 6,000 cGy, with treatment portal covering the site of recurrent dis ease.
by intraopema
tive implantation of 1-125 seeds has been used (4—6).It was believed that removal of the tumor and delivery of
extensive
of 1-125 recurrent
head and neck tumors. of
included examinations
base of the tongue; five, in the base of the skull; five, in the nasopharynx; four, in the parotid gland; three, in the maxillary sinus; and one, in the tonsillar fossa (Ta ble 1). Histologic types of the tumors in cluded squamous cell carcinoma in 35 pa tients, high-grade mucoepidermoid carci nomas in two patients, adenoid cystic
seeds to manage
Division
evaluation anesthesia,
radiation and, therefore, cannot tol erate a course of re-treatment with external beam radiation therapy. Of ten these patients are treated only with palliative therapy. The use of radioactive sources to treat cancer is nearly as old as the dis
intraoperative
the
The 25 men
and 16 women had a median age of 61 years (range, 24-90 years). Preoperative
were either unresectable or marginally resectable, due to the difficulty of achiev ing clear margins. Seventeen patients had recurrent disease in the neck; six, in the
Johns
I From
by intraopera
base of the skull, which precludes complete resection with clean man gins. Most of these patients have al ready received nearly toxic doses of
good local control with an acceptable rate of complications. This article me views the 10-year experience at The
Radiology 1991; 178:879—882
accompanied
tive 1-125 seed implantation.
AND
Therapy Surgery was performed to resect the me current carcinoma and to expose the tu mom bed for implantation. Microsurgery was performed to dissect tumors in a piecemeal fashion from bones, nerves, or major vessels, as necessary. Thus, in cer tam cases the resection margins of the specimen could not be evaluated. Howev
em,a majority of the patients were judged to have residual disease that was either macroscopic (grossly visible) or micro
scopic (having positive resection margins METHODS
at microscopy). ucts Division,
1-125 seeds (Medical Prod 3M, New Brighton, Minn)
were implanted
into the tumor bed intra
Otolaryngology (RIP.), The Johns Hopkins Hospital, Baltimore, MD 21205. Received May 18, 1990; revision requested July 10; revision
Patient Population
received September 17; accepted October 18. Address reprint requests to D.J.L.
tensive recurrent carcinomas of the head
operatively. An average of 24.7 seeds per implant, with 0.49 mCi of radioactivity per seed and average total radioactivity of 12.81 mCi, were used. The technique for
and neck were
seed implantation
@c) RSNA,
1991
From 1978 to 1988, 41 patients with ex treated
by means
of surgi
has been reported pre
879
viously
(7). The 1-125 seeds
were
implant
ed by means of single-seed inserters, with a spacing of 0.75-1 cm between adjacent seeds. The seeds were placed into the soft tissue of the tumor bed or onto patches of
Gelfoam (gelatin sponges; Upjohn, Kala mazoo, Mich), which were placed over the bone, nerve, or blood vessel involved with
disease.
Wounds
were
closed
either
primarily or with the establishment of a myocutaneous flap for reconstruction. Flaps were used in 18 (44%) of the cases. Perioperative prophylactic antibiotics were administered in all cases. After being judged medically stable, all patients were brought to the Department of Radiation Oncology, where orthogonal radiographs were obtained of verification, localization, culation of the 1-125 seeds.
for purposes and dose cal An example of
a localization radiograph showing 1-125 seeds implanted in the neck of a patient is shown in Figure 1. The locations of each of the implanted
orthogonal
seeds,
as shown
radiographs,
into a Capintec
on the
were digitahized
(Ramsey,
none between cal-regional
NJ) treatment
13 and 18 months, and
one between 19 and 24 months. The probability of remaining free of ho
recurrence
at 2 years was
planning computer. The total radiation dose delivered by the implant was calcu lated according to the methods reported
44% (Fig 3). Table
by Anderson (8) and Tokita et al (9). The total radiation dose delivered by the per manent 1-125 seeds implanted in a patient
Two patients devehoped only dis tant metastatic disease, while two
cannot be modified once the procedure completed
and the wound
average minimum tumor =
2,547)
is closed.
dose delivered
was 8,260 cGy (standard to an
12 cm3 (Table
average
Actuarial
cal-regional
is
The
to the
deviation volume
of
2).
No adjuvant
Statistical
tumor
recurrent
chemotherapy
was
given.
Analysis survival
ease control rates were analyzed by the methods of Kaplan and Meier (10). Re suits for all patients who survived the postoperative period were incorporated into the analysis. One patient died of sep sis and hypotension 3 days after resection
and 1-125 seed implantation current
carcinoma
to treat a re
in the base of the skull;
because no localization images had been taken for calculation of radiation dose, the case was excluded from statistical analysis.
1 shows
the sites
of
disease and the rate of ho
cGy was 57%, 47%, and 64%, mespec tively. No statistically significant con relation existed between the dose of implants and the mate of local recur
mence (P = .58, x2 test). Alternate
im
plant doses were analyzed, but no statistical correlation was noted.
rate for those
were 49% and 27%, respectively.
the use of flaps. This difference
When
statisticahly significant test). Major complications
tercumment disease, the determinate 2and 5-year survival rates were 59% (95% confidence interval of 47%— 71%) and 40% (95% confidence inter val of 19%—21%), respectively (Fig 2). All local-regional recurrences of tumors after this treatment became
manifest within 24 months. Sixteen patients developed recurrent disease within 6 months after the implanta tion, six between 7 and 12 months, 880 •¿ Radiology
Forty-five
to the implant dose to de
temmine any dose effect. The results showed that the local recurrence mate for patients with implant doses of less than 7,000 cGy, between 7,000 and 9,000 cGy, and more than 9,000
was 61% (11 of 18) versus 52% (12 of
due to in
nerve.
diation dose calculated for the 41 im plants was 8,260 cGy. In Table 2, pa tients were divided into three groups
The overall 2- and 5-year actuarial survival mates for the entire group for death
hypoglossal
An average of 24.7 seeds, each with 0.49 mCi of radioactivity, were im planted in 41 patients. The mean ma
The local recurrence
corrected
and
dis dis
patients who required the use of myocutaneous flap reconstruction
RESULTS
id artery
seeds were implanted.
control.
others developed locah recurrent ease, as well as distant metastatic ease.
according
rates and local dis
Figure 1. Lateral localization radiograph shows 1-125 seeds implanted in the left side of the neck of a patient with recurrent squa mous cell carcinoma that involved the carot
23) for patients
bined treatment
who did not require
is not
(P = .79, x2 of this com
with surgical mesec
tion and 1-125 seed implantation
were partial or total flap necrosis (24%), fistula formation (10%), carotid blowout (5%), and transient sepsis (5%) (Table 3). Flap necrosis, defined as partial on total fhap necrosis that required sum
gical removal of pant on all of the
flap, occurred
in 10 of the 18 patients
who underwent implantation and flap reconstruction. The flap failure rate was 56% and represented the total patient population.
24% of The time
of flap failure ranged from 2 weeks to 12 weeks, with an average time of 4.2 weeks. The average radiation dose delivered to the flap at the time of failure was 3,200 cGy (standard de viation = 1,200). Fistulas developed in four (10%) cases and required surgical manage ment for proper closure. One patient had difficulty with his fistuha until his death. Carotid blowout occurred in two patients; the onset of bleeding was noted by staff, and the patients were immediately taken to surgery. They survived their episodes. Osteoradionecrosis occurred in one
case, and the area was surgically
ex
cised and replaced with a prosthesis. None of these complications was fatal. (As previously noted, however, one patient died of sepsis and hypo
March 1991
@
oL@@
@ !@ :@ @
@:LL@
moms in the tonsil @
I
.
on soft palate
are
more accessible and are probably more localized than those tumors treated in our series. Complications
L
of soft-tissue necrosis, osteonadione crosis, and phamyngocutaneous fistu ha occurred in 23% of the patients (14). Our complication
mate is similar
to that in their study. ThE (@th)
The difficulty of placing 1-125 seeds onto bones, nerves, on the ca motid artery has been recognized and
TIE 5nci*)
2.
3.
Figure 2. Graphs illustrate (2) determinate actuarial survival rates and (3) local control rates for 41 patients with recurrent head and neck tumors following 1-125seed implantation ther apy.
resolved independently by several investigators with the use of absorb able sutures as carriers for the radio active seeds (15—17).In our study, a different approach was used. When indicated,
Permanent 1-125 seed implants have been used to treat recurrent head and neck carcinomas. However, the use of implants alone did not im prove long-term survival significant ly. Viknam et al reported
good initial
response, with 71% complete me sponse mates and 18% partial response rates in 118 patients who received I125 seed implants
for recurrent
head
and neck cancer (13). However, survival
tension
3 days after undergoing
im
plantation.)
gery (4). Goffinet
seeds containing
Rn
222 or gold-198 have long been used as permanent interstitial implants to
treat head and neck cancers (1,2,1 1). The advantage of limiting the dose of radiation to tumor-bearing sites by the use of interstitial implants makes this approach suitable for the treat
ment of recurrent head and neck car cinomas in patients who had previ ously received
high-dose
beam radiation
therapy.
external
after the introduction
of I-
125, Rn-222, and Ir-192 seeds used to treat patients with metastatic neck lymph nodes or lung cancer. They
found that the iodine seed had the lowest complication rate (17%) and the highest local control mate (78%) in surviving
4 months
Volume 178 •¿ Number 3
intraoperative
et al reported
that
1-125 seed implanta
tion into the pterygo-palatine
fossa
and/on base of the skull had achieved local control of disease in six of 10 previously untreated, as well as four
of five recurrent, advanced head and neck neoplasms (5). In another study, Fee et al reported the use of intmaop enative 1-125 implants for the treat ment of 29 patients with advanced (1 1 patients) or recurrent (18 pa tients) tumors in the neck that were
125 seeds in the 1970s, the reduced radiation exposure to medical per sonnel and the patient's family, due to the low energy (27 kV) gamma ray of 1-125, was soon appreciated (3). Kim and Hilanis compared the local control and complication mates of I-
patients (12).
head and neck
cancer who were treated with intra operative 1-125 implantation and sum
DISCUSSION
Shortly
and 5.5% at 5 years (13). A better sun vival mate was achieved when 1-125 seed implantation was combined with surgical resection. Martinez et al reported a 17% 2-year survival mate and 50% local control rate in 17 pa tients with recurrent
Radioactive
the
mate was only 9% at 2 years
or more
attached to the carotid artery. With a minimum
follow-up
of 1 year, 62% of
patients were disease-free
in the en
tire neck (6). In 12 (41%) patients,
nine minor and eight major comphi cations developed (6). Our results
determinate similar
of 27% overall
and 40%
5-year survival mates are
to those reported
mate without
artery,
on
tissue in the tumor
bed, and only
when necessary were the Gelfoam patches used. We found this method to be very useful, especially for coy ening the bony base of the skull. One of the issues in the manage ment of advanced recurrent head and neck carcinomas is the quality of life. All of the patients in this series suf fered from disease-related symptoms, particularly
intractable
pain. Partial
or total relief from pain was achieved in the majority of patients by means of surgical resection of their disease.
Intmaopemative implantation
of the I-
125 seeds to combat any macroscopic or microscopic residual disease might
have contributed
to the long-term
ho
cal control of the disease in some cases. In conclusion, our study showed
that surgical resection with intraop emative 1-125 seed implantation is a potentially
curative
treatment
with
acceptable risks of complications patients
with recurrent
for
advanced
head and neck carcinomas that would have been judged unresect able and who would have been treat ed only with palliative therapy. The use of this approach to manage previ ously untreated, locally advanced disease (such as involvement of the
carotid artery or erosion of the base of the skull) is currently under inves tigation. U
by Putha
wala et al (14). They reported that me current on persistent carcinomas of the tonsil or soft palate could be treated with Im-192 implants and that a 72% local control rate, with a 42% 2year survival
the bone, carotid
nerves were covered with small patches of Gelfoam (1 cm wide and several centimeters long), onto which the 1-125 seeds were placed. Wherever possible, the 1-125 seeds were inserted directly into the soft
recurrent
disease, was achieved. However, tu
References 1.
Bloedorn
FG, Cuccia
CA, Mercado
The place of interstitial
2.
gamma-ray
R Jr.
emit
ters in radiation therapy: indications, techniques, examples. AJR 1961; 85:407477. Pierquin B. The destiny of brachytherapy in oncology. AJR 1976; 127:495-499.
Radiology •¿ 881
3.
4.
5.
Hilaris BS, Holt GS, St Germain J. The use of iodine-125 for interstitial implants. U.S. Department of Health, Education and Welfare publication (FDA) 76-8022. Rock ville, Md: U.S. Food and Drug Adminis tration; 1975. Martinez A, Goffinet DR. Fee W, Goode R, Cox RS. Iodine-l25 implants as an adju vant to surgery and external beam radio therapy in the management of locally ad vanced head and neck cancer. Cancer 1983; 51:973—979. Goffinet
DR. Martinez
A, Pooler
D, Fee
WE, Levine PA. Intraoperative pterygo palatine interstitial iodine-125 seed im plants. Int J Radiat Oncol Biol Phys 1983; 9:103-106.
6.
Fee WE, Goffinet DR. Paryani 5, Goode RL, Levine PA, Hoppe ML. Intraopera tive iodine-125 implants. Arch Otolaryn gol Head Neck Surg 1983; 109:727-730.
882 •¿ Radiology
7.
8.
Lee DJ. Radiotherapy: adjuvant to man agement of malignant skull-base tumors. Ear Nose Throat J 1986; 65:58-62. Anderson L. Spacing nomograph for in terstitial implants of t251 seeds. Med Phys
1976; 3:48—51. 9. Tokita N, Kim J, Hilaris B. Time-dose volume considerations in 251interstitial brachytherapy. Int J Radiat Oncol Biol Phys 1980; 6:1745-1749. 10. Kaplan EL, Meier PJ. Nonparametric esti mation from incomplete observations. Am Stat Assoc 1958; 53:457-481. 11. Seydel HG, Scholl H. Permanent im plants in the management of head and neck cancer by radiotherapy. AJR 1973; 117:565-574. 12. Kim JH, Hilaris BS. Iodine-125 sources in interstitial tumor therapy: clinical and biologic considerations. AJR 1975; 123:163-169.
13.
14.
15.
Vikram
B, Hilaris
BS, Anderson
L, Strong
EW. Permanent iodine-l25 implants in head and neck cancer. Cancer 1983; 51: 1310—1314. Puthawala AA, Syed MN, Gates TC. Iridi um-l92 implants in the treatment of ton sillar region malignancies. Arch Otolaryn gol Head Neck Surg 1985; 111:812—815. Harter DJ, Declos L, Johns MF. Sealed sources
in synthetic
absorbable
suture:
a
new technology for permanent interstitial implantation. Radiology 1975; 116:721723.
16.
Goffinet DR. Schneider MJ, Glatstein EL, et al. Bladder cancer: results in radiother apy in 384 patients. Radiology 1975; 117:149-153.
17.
Scott Wi'.
Interstitial
therapy
using
non
absorbable (Ir'92 nylon ribbon) and ab sorbable (1125Vicryl) suturing techniques. AJR 1975; 124:560-564.
March 1991
Intraoperative 1-125 Seed Implantation for Extensive Recurrent Head and Neck Carcinomas' From 1978 to 1988, 41 patients with extensive recurrent carcinomas of the head and neck were treated with surgical resection plus intraopera tive iodine-125 seed implantation. Surgery
was performed
to resect
the
tumors and to expose the tumor beds for implantation. 1-125 seeds were implanted intraoperatively, with a spacing of 0.75-1 cm between adjacent seeds, either into the soft tissue in the tumor bed or onto small patches of gelatin sponges to cover the bone, nerve, or blood yes sel involved with disease. Recon structive flaps were used in 18 pa tients. The average 1-125 dose deliv ered by the implanted seeds was 8,263 cGy. The determinate 5-year actuarial survival rate for the entire group was 40%. The 5-year local dis ease control rate was 44%. Major complications were transient wound infection (32%), flap necrosis (24%), fistula formation (10%), and carotid blowout (5%). These results indicate that surgical resection plus 1-125 seed implantation provides a poten tially curative treatment for patients with extensive recurrent head and neck carcinomas that would be con sidered traditionally unresectable and that would be treated only with palliative therapy. Index terms: 28.37, 20.452,
Head and neck neoplasms, 20.454 •¿ Radionuclides,
tic, 20.452 •¿ Therapeutic
radiology,
therapeu
20.452
T
HE management
of recurrent
cal resection
head and neck carcinoma is a problem often faced by radiation on cologists and head and neck sum geons. Such tumors frequently in
volve deep neck structures
or the
covery
of radionuclides
themselves.
Radium-226, radon-222, inidiurn-192, and iodine-125 are just some of the radioactive sources that have been used in interstitial
radiation
The use of radionuclides advantage of delivering
therapy.
offers the a high dose
of radiation
to a localized
area while
minimizing
the dose to surrounding
tissue (1—3).
In patients with extensive recur rent head and neck carcinomas,
sun
vival rates remain poor, and the ma jon cause of death
is still local disease.
Surgical resection of the bulk of the disease
accompanied
Radiation
Oncology
(D.J.L., F.Z.L., E.S.Z.) and the Department of
panendoscopies,
under
biopsies,
and
CT and/or MR imaging. All of these cases
high-dose, localized radiation to the tumor-bearing area would achieve
Hopkins
Hospital
of the use of
implantation
MATERIALS
carcinoma in two patients, and one case
each of malignant melanoma and malig nant
mixed
tumor.
The original
stages
of
cancer were stage I in two cases (5%), stage II in seven (17%), stage III in 11 (27%), and stage IV in 21 (51%). However, the original stage did not reflect the ad
vanced nature of recurrence
in these pa
tients. All patients, except those whose original tumor was in the nasopharynx, initially underwent surgical resection. Thirty-eight (93%) received a course of
external-beam
radiation therapy, with a
median dose of 6,000 cGy, with treatment portal covering the site of recurrent dis ease.
by intraopema
tive implantation of 1-125 seeds has been used (4—6).It was believed that removal of the tumor and delivery of
extensive
of 1-125 recurrent
head and neck tumors. of
included examinations
base of the tongue; five, in the base of the skull; five, in the nasopharynx; four, in the parotid gland; three, in the maxillary sinus; and one, in the tonsillar fossa (Ta ble 1). Histologic types of the tumors in cluded squamous cell carcinoma in 35 pa tients, high-grade mucoepidermoid carci nomas in two patients, adenoid cystic
seeds to manage
Division
evaluation anesthesia,
radiation and, therefore, cannot tol erate a course of re-treatment with external beam radiation therapy. Of ten these patients are treated only with palliative therapy. The use of radioactive sources to treat cancer is nearly as old as the dis
intraoperative
the
The 25 men
and 16 women had a median age of 61 years (range, 24-90 years). Preoperative
were either unresectable or marginally resectable, due to the difficulty of achiev ing clear margins. Seventeen patients had recurrent disease in the neck; six, in the
Johns
I From
by intraopera
base of the skull, which precludes complete resection with clean man gins. Most of these patients have al ready received nearly toxic doses of
good local control with an acceptable rate of complications. This article me views the 10-year experience at The
Radiology 1991; 178:879—882
accompanied
tive 1-125 seed implantation.
AND
Therapy Surgery was performed to resect the me current carcinoma and to expose the tu mom bed for implantation. Microsurgery was performed to dissect tumors in a piecemeal fashion from bones, nerves, or major vessels, as necessary. Thus, in cer tam cases the resection margins of the specimen could not be evaluated. Howev
em,a majority of the patients were judged to have residual disease that was either macroscopic (grossly visible) or micro
scopic (having positive resection margins METHODS
at microscopy). ucts Division,
1-125 seeds (Medical Prod 3M, New Brighton, Minn)
were implanted
into the tumor bed intra
Otolaryngology (RIP.), The Johns Hopkins Hospital, Baltimore, MD 21205. Received May 18, 1990; revision requested July 10; revision
Patient Population
received September 17; accepted October 18. Address reprint requests to D.J.L.
tensive recurrent carcinomas of the head
operatively. An average of 24.7 seeds per implant, with 0.49 mCi of radioactivity per seed and average total radioactivity of 12.81 mCi, were used. The technique for
and neck were
seed implantation
@c) RSNA,
1991
From 1978 to 1988, 41 patients with ex treated
by means
of surgi
has been reported pre
879
viously
(7). The 1-125 seeds
were
implant
ed by means of single-seed inserters, with a spacing of 0.75-1 cm between adjacent seeds. The seeds were placed into the soft tissue of the tumor bed or onto patches of
Gelfoam (gelatin sponges; Upjohn, Kala mazoo, Mich), which were placed over the bone, nerve, or blood vessel involved with
disease.
Wounds
were
closed
either
primarily or with the establishment of a myocutaneous flap for reconstruction. Flaps were used in 18 (44%) of the cases. Perioperative prophylactic antibiotics were administered in all cases. After being judged medically stable, all patients were brought to the Department of Radiation Oncology, where orthogonal radiographs were obtained of verification, localization, culation of the 1-125 seeds.
for purposes and dose cal An example of
a localization radiograph showing 1-125 seeds implanted in the neck of a patient is shown in Figure 1. The locations of each of the implanted
orthogonal
seeds,
as shown
radiographs,
into a Capintec
on the
were digitahized
(Ramsey,
none between cal-regional
NJ) treatment
13 and 18 months, and
one between 19 and 24 months. The probability of remaining free of ho
recurrence
at 2 years was
planning computer. The total radiation dose delivered by the implant was calcu lated according to the methods reported
44% (Fig 3). Table
by Anderson (8) and Tokita et al (9). The total radiation dose delivered by the per manent 1-125 seeds implanted in a patient
Two patients devehoped only dis tant metastatic disease, while two
cannot be modified once the procedure completed
and the wound
average minimum tumor =
2,547)
is closed.
dose delivered
was 8,260 cGy (standard to an
12 cm3 (Table
average
Actuarial
cal-regional
is
The
to the
deviation volume
of
2).
No adjuvant
Statistical
tumor
recurrent
chemotherapy
was
given.
Analysis survival
ease control rates were analyzed by the methods of Kaplan and Meier (10). Re suits for all patients who survived the postoperative period were incorporated into the analysis. One patient died of sep sis and hypotension 3 days after resection
and 1-125 seed implantation current
carcinoma
to treat a re
in the base of the skull;
because no localization images had been taken for calculation of radiation dose, the case was excluded from statistical analysis.
1 shows
the sites
of
disease and the rate of ho
cGy was 57%, 47%, and 64%, mespec tively. No statistically significant con relation existed between the dose of implants and the mate of local recur
mence (P = .58, x2 test). Alternate
im
plant doses were analyzed, but no statistical correlation was noted.
rate for those
were 49% and 27%, respectively.
the use of flaps. This difference
When
statisticahly significant test). Major complications
tercumment disease, the determinate 2and 5-year survival rates were 59% (95% confidence interval of 47%— 71%) and 40% (95% confidence inter val of 19%—21%), respectively (Fig 2). All local-regional recurrences of tumors after this treatment became
manifest within 24 months. Sixteen patients developed recurrent disease within 6 months after the implanta tion, six between 7 and 12 months, 880 •¿ Radiology
Forty-five
to the implant dose to de
temmine any dose effect. The results showed that the local recurrence mate for patients with implant doses of less than 7,000 cGy, between 7,000 and 9,000 cGy, and more than 9,000
was 61% (11 of 18) versus 52% (12 of
due to in
nerve.
diation dose calculated for the 41 im plants was 8,260 cGy. In Table 2, pa tients were divided into three groups
The overall 2- and 5-year actuarial survival mates for the entire group for death
hypoglossal
An average of 24.7 seeds, each with 0.49 mCi of radioactivity, were im planted in 41 patients. The mean ma
The local recurrence
corrected
and
dis dis
patients who required the use of myocutaneous flap reconstruction
RESULTS
id artery
seeds were implanted.
control.
others developed locah recurrent ease, as well as distant metastatic ease.
according
rates and local dis
Figure 1. Lateral localization radiograph shows 1-125 seeds implanted in the left side of the neck of a patient with recurrent squa mous cell carcinoma that involved the carot
23) for patients
bined treatment
who did not require
is not
(P = .79, x2 of this com
with surgical mesec
tion and 1-125 seed implantation
were partial or total flap necrosis (24%), fistula formation (10%), carotid blowout (5%), and transient sepsis (5%) (Table 3). Flap necrosis, defined as partial on total fhap necrosis that required sum
gical removal of pant on all of the
flap, occurred
in 10 of the 18 patients
who underwent implantation and flap reconstruction. The flap failure rate was 56% and represented the total patient population.
24% of The time
of flap failure ranged from 2 weeks to 12 weeks, with an average time of 4.2 weeks. The average radiation dose delivered to the flap at the time of failure was 3,200 cGy (standard de viation = 1,200). Fistulas developed in four (10%) cases and required surgical manage ment for proper closure. One patient had difficulty with his fistuha until his death. Carotid blowout occurred in two patients; the onset of bleeding was noted by staff, and the patients were immediately taken to surgery. They survived their episodes. Osteoradionecrosis occurred in one
case, and the area was surgically
ex
cised and replaced with a prosthesis. None of these complications was fatal. (As previously noted, however, one patient died of sepsis and hypo
March 1991
@
oL@@
@ !@ :@ @
@:LL@
moms in the tonsil @
I
.
on soft palate
are
more accessible and are probably more localized than those tumors treated in our series. Complications
L
of soft-tissue necrosis, osteonadione crosis, and phamyngocutaneous fistu ha occurred in 23% of the patients (14). Our complication
mate is similar
to that in their study. ThE (@th)
The difficulty of placing 1-125 seeds onto bones, nerves, on the ca motid artery has been recognized and
TIE 5nci*)
2.
3.
Figure 2. Graphs illustrate (2) determinate actuarial survival rates and (3) local control rates for 41 patients with recurrent head and neck tumors following 1-125seed implantation ther apy.
resolved independently by several investigators with the use of absorb able sutures as carriers for the radio active seeds (15—17).In our study, a different approach was used. When indicated,
Permanent 1-125 seed implants have been used to treat recurrent head and neck carcinomas. However, the use of implants alone did not im prove long-term survival significant ly. Viknam et al reported
good initial
response, with 71% complete me sponse mates and 18% partial response rates in 118 patients who received I125 seed implants
for recurrent
head
and neck cancer (13). However, survival
tension
3 days after undergoing
im
plantation.)
gery (4). Goffinet
seeds containing
Rn
222 or gold-198 have long been used as permanent interstitial implants to
treat head and neck cancers (1,2,1 1). The advantage of limiting the dose of radiation to tumor-bearing sites by the use of interstitial implants makes this approach suitable for the treat
ment of recurrent head and neck car cinomas in patients who had previ ously received
high-dose
beam radiation
therapy.
external
after the introduction
of I-
125, Rn-222, and Ir-192 seeds used to treat patients with metastatic neck lymph nodes or lung cancer. They
found that the iodine seed had the lowest complication rate (17%) and the highest local control mate (78%) in surviving
4 months
Volume 178 •¿ Number 3
intraoperative
et al reported
that
1-125 seed implanta
tion into the pterygo-palatine
fossa
and/on base of the skull had achieved local control of disease in six of 10 previously untreated, as well as four
of five recurrent, advanced head and neck neoplasms (5). In another study, Fee et al reported the use of intmaop enative 1-125 implants for the treat ment of 29 patients with advanced (1 1 patients) or recurrent (18 pa tients) tumors in the neck that were
125 seeds in the 1970s, the reduced radiation exposure to medical per sonnel and the patient's family, due to the low energy (27 kV) gamma ray of 1-125, was soon appreciated (3). Kim and Hilanis compared the local control and complication mates of I-
patients (12).
head and neck
cancer who were treated with intra operative 1-125 implantation and sum
DISCUSSION
Shortly
and 5.5% at 5 years (13). A better sun vival mate was achieved when 1-125 seed implantation was combined with surgical resection. Martinez et al reported a 17% 2-year survival mate and 50% local control rate in 17 pa tients with recurrent
Radioactive
the
mate was only 9% at 2 years
or more
attached to the carotid artery. With a minimum
follow-up
of 1 year, 62% of
patients were disease-free
in the en
tire neck (6). In 12 (41%) patients,
nine minor and eight major comphi cations developed (6). Our results
determinate similar
of 27% overall
and 40%
5-year survival mates are
to those reported
mate without
artery,
on
tissue in the tumor
bed, and only
when necessary were the Gelfoam patches used. We found this method to be very useful, especially for coy ening the bony base of the skull. One of the issues in the manage ment of advanced recurrent head and neck carcinomas is the quality of life. All of the patients in this series suf fered from disease-related symptoms, particularly
intractable
pain. Partial
or total relief from pain was achieved in the majority of patients by means of surgical resection of their disease.
Intmaopemative implantation
of the I-
125 seeds to combat any macroscopic or microscopic residual disease might
have contributed
to the long-term
ho
cal control of the disease in some cases. In conclusion, our study showed
that surgical resection with intraop emative 1-125 seed implantation is a potentially
curative
treatment
with
acceptable risks of complications patients
with recurrent
for
advanced
head and neck carcinomas that would have been judged unresect able and who would have been treat ed only with palliative therapy. The use of this approach to manage previ ously untreated, locally advanced disease (such as involvement of the
carotid artery or erosion of the base of the skull) is currently under inves tigation. U
by Putha
wala et al (14). They reported that me current on persistent carcinomas of the tonsil or soft palate could be treated with Im-192 implants and that a 72% local control rate, with a 42% 2year survival
the bone, carotid
nerves were covered with small patches of Gelfoam (1 cm wide and several centimeters long), onto which the 1-125 seeds were placed. Wherever possible, the 1-125 seeds were inserted directly into the soft
recurrent
disease, was achieved. However, tu
References 1.
Bloedorn
FG, Cuccia
CA, Mercado
The place of interstitial
2.
gamma-ray
R Jr.
emit
ters in radiation therapy: indications, techniques, examples. AJR 1961; 85:407477. Pierquin B. The destiny of brachytherapy in oncology. AJR 1976; 127:495-499.
Radiology •¿ 881
3.
4.
5.
Hilaris BS, Holt GS, St Germain J. The use of iodine-125 for interstitial implants. U.S. Department of Health, Education and Welfare publication (FDA) 76-8022. Rock ville, Md: U.S. Food and Drug Adminis tration; 1975. Martinez A, Goffinet DR. Fee W, Goode R, Cox RS. Iodine-l25 implants as an adju vant to surgery and external beam radio therapy in the management of locally ad vanced head and neck cancer. Cancer 1983; 51:973—979. Goffinet
DR. Martinez
A, Pooler
D, Fee
WE, Levine PA. Intraoperative pterygo palatine interstitial iodine-125 seed im plants. Int J Radiat Oncol Biol Phys 1983; 9:103-106.
6.
Fee WE, Goffinet DR. Paryani 5, Goode RL, Levine PA, Hoppe ML. Intraopera tive iodine-125 implants. Arch Otolaryn gol Head Neck Surg 1983; 109:727-730.
882 •¿ Radiology
7.
8.
Lee DJ. Radiotherapy: adjuvant to man agement of malignant skull-base tumors. Ear Nose Throat J 1986; 65:58-62. Anderson L. Spacing nomograph for in terstitial implants of t251 seeds. Med Phys
1976; 3:48—51. 9. Tokita N, Kim J, Hilaris B. Time-dose volume considerations in 251interstitial brachytherapy. Int J Radiat Oncol Biol Phys 1980; 6:1745-1749. 10. Kaplan EL, Meier PJ. Nonparametric esti mation from incomplete observations. Am Stat Assoc 1958; 53:457-481. 11. Seydel HG, Scholl H. Permanent im plants in the management of head and neck cancer by radiotherapy. AJR 1973; 117:565-574. 12. Kim JH, Hilaris BS. Iodine-125 sources in interstitial tumor therapy: clinical and biologic considerations. AJR 1975; 123:163-169.
13.
14.
15.
Vikram
B, Hilaris
BS, Anderson
L, Strong
EW. Permanent iodine-l25 implants in head and neck cancer. Cancer 1983; 51: 1310—1314. Puthawala AA, Syed MN, Gates TC. Iridi um-l92 implants in the treatment of ton sillar region malignancies. Arch Otolaryn gol Head Neck Surg 1985; 111:812—815. Harter DJ, Declos L, Johns MF. Sealed sources
in synthetic
absorbable
suture:
a
new technology for permanent interstitial implantation. Radiology 1975; 116:721723.
16.
Goffinet DR. Schneider MJ, Glatstein EL, et al. Bladder cancer: results in radiother apy in 384 patients. Radiology 1975; 117:149-153.
17.
Scott Wi'.
Interstitial
therapy
using
non
absorbable (Ir'92 nylon ribbon) and ab sorbable (1125Vicryl) suturing techniques. AJR 1975; 124:560-564.
March 1991
