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Interstitial irradiation in recurrent gynecological cancer
Inr. 1. Radiation tiologv Bid. Phys., Vol. 1. pp. 15134517 Printed in the U.S.A. All rights rcaervcd.
03s(r3016/S1/111513~5~2.~/0 Copyrisht 0 1981 Pngamon Press Ltd.
??Original Contribution INTERSTITIAL IRRADIATION IN RECURRENT GYNECOLOGICAL CANCER D. NORI, M.D.,* B.S. HILARIS, M.D.,* H.S. KIM, M.D.,* D.G. CLARK, M.D.,? W.S.
KIM, M.D.,7
W.B.
Memorial Sloan-Kettering
JONES, M.D.?
AND J.L.
LEWIS JR.,
M.D.?
Cancer Center, 1275 York Ave., New York, NY 10021
Ninety-six patients with recurrent gynecological, cancer documented by biopsy underwent interstitial implantation at Memorial Sloan-Kettering Cancer Center during the period of 1957-1976. They are divided into two groups: Group I includes 75 patients with recurrent cervical cancer and Group If includes 21 patients with otber recurrent gynecological cancer. In Group I, 63 % (47) had previously received a full course of both external and intracavitary radiation, 22 % (17) had surgery and 12 % (9) had both sugery and radiation as prior management for their primary disease. In two patients, the prior management was not clearly documented. Symptomatic relief was obtained in 70% of the patients who initially presented with symptoms. Without subsequent treatment, 34 of these 75 (45%) patients were alive and disease-free at one year, 15 (20 % ) at two years, 12 (16 56) at three years, 9 (12 96) at four years and 7 (10% ) at five years. In Group If,48 %I (10) were alive and disease free at one year, 33 % (7) at two years, 24 % (5) at three years, 19 % (4) at four years and 5 % (1) at five years. Interstitial implant, Gynecological cancer, Radioiostopes.
patients) and with other primary urethra and ureter) (5 patients).
INTRODUCTION Interstitial implantation of radioactive materials is useful in the management of localized cancer. This technique allows the delivery of a much higher dose to the tumor
cancers
(vagina,
Group I (recurrent cancer of the cervix) Ninety-eight percent of the patients in this group had an epidermoid carcinoma; one patient had an adenocarcinoma. The median age was 55 years; the range was 21-70 years. Table 1 shows the stage at the initial diagnosis; 49% of the patients had Stage I & II carcinoma of the cervix. In 29 patients the initial stage was not available, as these patients were initially seen elsewhere. Forty-seven of the 75 patients (63%) were initially treated by radiation. This consisted of external beam therapy (2 patients), intracavitary irradiation (5 patients) and a combination of the two (40 patients). Surgery was used in the intitial management in 17 patients (22%). Surgery and radiation was used in 9 patients (12%). In the remaining 2 patients (3%), the type of previous treatment was not clearly documented. In 18 patients (24%), the recurrence was diagnosed within 6 months after the initial treatment. Seventy percent of all recurrences were observed within the first two years after initial treatment. Table 2 shows symptoms and signs observed at the time of recurrence. Pain (abdominal, pelvic and/or leg) was the most frequently mentioned symptom by these patients (80%). Swelling of lower extremities, vaginal
than is possible with external radiation, and gives a lower dose to the adjoining normal tissues. It is possible to use this technique in selected cases of recurrent gynecological cancer, recurring locally after a full course of external radiation, intracavitary radiation, surgery or a combination of these. Interstitial irradiation has been used at Memorial Hospital as an alternative method of treatment in patients with unresectable recurrent gynecological malignancies. Our earlier experience with intersitial irradiation in cancer of the cervix was reported in 1971. This present review includes all patients with recurrent gynecological malignancies treated by interstitial irradiation in our institution during a 20 year period.
METHODS AND MATERIALS From 1957-1976, 96 patients with recurrent gynecological cancers documented by biopsy underwent interstitial implantation. They are divided into two groups. Group I consists of 75 patients with recurrent cervical cancer and Group II consists of 21 patients with various other recurrent gynecological cancers from endometrial primary (7 patients), ovarian (6 patients), vulvar (3
Service, Department of Radiation Therapy. tGynecology Service, Department of Surgery.
Reprint request to: D. Nori, M.D. Accepted for publication 9 July 198 1.
*Brachytherapy
1513
Radiation Oncology 0 Biology 0 Physics
1514 Table
November 1981, Volume 7, Number I 1
1. Interstitial irradiation in recurrent gynecological cancer (Group
No.
No. of patients
Percent
II III IV
I3 23 6 4
I8 31 8 5
Unknown
29
38
Initial stage of disease Stage Stage Stage Stage
I
Table 3. Interstitial irradiation in recurrent gynecological cancer
I)
Unilateral pelvic side walls Pelvic side wall, para aortic and/or parametriae Vaginal Bilateral pelvic side walls Pelvic side wall and vagina Perineal
and/or rectal bleeding and palpable abdominal were less frequently observed. Twelve patients asymptomatic and the diagnosis of recurrence was on routine follow-up examination. Management. A histological confirmation of the rence was obtained prior to interstitial implantation 75 patients.
Sixty
of these
patients
underwent
mass were made recurin all
an explor-
in order to determine the extent of the disease. In the remaining 15 patients, the diagnosis was obtained by direct punch biopsy of the accessible tumor in the vagina or the perineum. Thirty-three of the 60 patients who underwent an exploratory laparotomy had disease limited to the pelvis (one or both side walls); the remaining 27 patients had para-aortic nodal involvement as well. Table 3 lists the site of implantation in all 75 patients. An attempt was made to implant all of the disease; however, this was not always possible when the disease had extended outside the pelvis to involve the para-aortic nodes. During this period different radioiostopes were used for interstitial implantation such as Iridium- 192, Radon222. Au- 198 and Iodine- 125. Permanent intersitial implants were favored and only occasional temporary implants were performed; Ir- 192 was used in 39 patients, (30 permanent and 9 temporary implants); Rn-222 in 12 patients, Au-l 98 in 1 patient, and more recently, I- 125 in 23 patients. The dose ranged from 20,000-30,000 rad if Iridium seeds were used or approximately half of this atory
laparotomy,
which
was performed
patients
Percent
32
43
17 13 7 4 2
23 I7 9 5 3
dose if Gold and Radon were used. When Iridium-192 was used for removable implant, the dose was prescribed at 0.5 cm from the plane of the implant and the total dose ranged from 4000-5000 rad in 4-5 days. Computer calculated isodose curves were obtained routinely at various planes in the last 10 years using the Memorial Hospital Computer Brachy Program. The MPD (minimal peripheral dose) with I-125 varied from 130-160 Gy. Partial resection of the tumor was performed in 17/75 patients (23%). In addition to interstitial implantation, various surgical procedures such as abdominal hysterectomy, bowel resection and transvesicle ureteroneocystomies for totally obstructed ureters were performed. Post-operative external pelvic radiation (4OOCL5000 rad in 4-4’/2 weeks) was given to 7 patients, either because all of the disease was not implanted, or because the dose distribution resulting from the implant was considered unsatisfactory. Mortality and morbidity. Four patients (5.3%) died
INTERSTITIAL IRRADIATION IN RECURRENT 6INECOlOOlCAL CANCER
Table 2. Interstitial
irradiation in recurrent gynecological cancer presenting signs and symptoms No. patients
Pain (pelvic) Pain and swelling of leg R.E. & asymptomatic Pain and abnormal I.V.P. Abnormal I.V.P. Vaginal bleeding Rectal bleeding Abdominal mass R.E. gram.
= Routine
examination;
Percent
36175 16115
12175 6175 6175 5175 3175 l/75 I.V.P.
= Intravenous
48 21 I6 8 8 6 4
1 pyelo-
1
2
3
4
5
6
Survival Post Implant (yrs)
Fig. 1. Survival tion.
of patients
treated
with interstitial
implanta-
7
Recurrent gynecologic cancer 0 D. NORIet ul.
INTERSTITIAL IRRADIATION IN RECURRENT 6YNECOLO6ICAL CANCER loo 80
Negative para-aortic Positive para-aortic
---
60 \ m \
20% u Z E lo8g $ 6g
-\ \
-----
(27)
I
I
I
I
I
t
1
2
3
4
5
Survival
within 30 days after laparotomy and implantation. In 3 patients, death was caused by pulmonary embolism; the fourth patient died of septicemia following evisceration. All post-operative deaths occurred in patients treated prior to 1967. Early complications (within the first 30 days) were observed in 10 other patients as follows: Thrombophlebitis of the lower extremities in 2 patients; perineal cellulitis in 2; urinary incontinence in 1 patient, urinary tract infection in 1 patient; and fever of unknown etiology in 4
Table 4. Survival in group II Survival
site
Endometrium Ovary Vulva Other (vagina, urethra, ureter) Total
patients. All of these reactions were transient and subsided after conservative management within 4 weeks. Late complications were observed in 5 patients as follows: Partial bowel obstruction in 2 patients; rectovaginal fistula in 1 patient; and radiation proctitis in 2 patients. These complications required surgical intervention in all 5 patients. Survival. Thirty-four of the 75 patients (45%) were alive and disease-free one year after implantation; and seven patients (10%) were alive and disease-free at 5 years after treatment. The median survival was 11 months. Patients with disease limited to the vagina, cervix or periurethral region had a better median survival (18 months) and 5 year survival (3 1%) (Figure 1). Figure 2 shows the survival rate for the 60 patients who underwent a laparotomy; 27 were found to have metastatic cervical carcinoma in the para-aortic nodes. The median survival was 6 months with involvement of the para-aortic nodes, and 18 months without, respectively. The 5 year survival in patients with positive nodes was 3% and 7% for the patients with negative nodes. Pain relief was obtained in 36/52 patients (70%) who had extensive pelvic side wall involvement that caused pain associated with evidence of the lower extremities swelling. The swelling itself was improved in 44% (7/ 16). Vaginal or rectal bleeding was improved in all 8 patients who presented with this symptom.
Post Implant (yrs)
Fig. 2. Survival data in patients with positive and negative para-aortic nodes.
Primary
1515
No. of patients
Median (months)
Range (months)
I 6 3
18 9.5 12
(O-61) (o-38) (o-36)
5
30
(7-48)
21
11
O-61 months
Group II (other recurrent gynecological cancers) This group consists of 21 patients with recurrent noncervical gynecological cancers with primary endometrial carcinomas (7 patients), ovarian (6 patients), vulvar (3 patients), vagina, and others (5 patients). Prior management included surgery and radiation in 14 patients (62%); surgery alone in 5 patients (24%) and radiation alone in 2 patients (4%). Iridium 192 was used in 6 patients and Iodine 125 in 15 patients. The implanted sites were as follows: vulva (1 patient), vagina (5 patients), pelvis (14 patients) and abdomen (I patient). No post-operative deaths occurred in this group. Table 4 shows the survival (median and range) in the
INTERSTITIAL IRRADIATION IN RECURRENT GYNECOLOGICAL CANCER Suggested Prognostic Factors Favorable:
1) Asymptomatic recurrence detected routine examination 2) Vaginal recurrences 3) Unilateral pelvic side wall involvement
Unfavorable:
1) Pelvic pain with leg edema 2) Multiple sites of recurrence in the pelvis 3) Positive para aortic nodes Fig. 3. Suggested
prognostic
factors.
1516
Radiation Oncology 0 Biology 0 Physics
Fig. 4. Fifty-five year-old white female who presented with ca of the cervix, Stage IIA, who underwent a radical hysterectomy and pelvic node dissection in 1970. This patient presented with a 5 x 5 x 4 cm pelvic side wall recurence, treated by permanent I-l 25 interstitial implantation.
of this group. The overall median survival was 11 months; one patient has survived over 5 years at last follow-up and was free of disease.
21 patients
DISCUSSION Recurrent cancer at any site spells gloomy prognosis. Cancer of the cervix that recurs after radical surgery or curative radiation therapy is a perplexing problem confronting both Gynecological & Radiation Oncologists. In many centers, oncologists are not enthusiastic to re-treat these patients, as they consider re-treatment futile. A review of the literature, however, reveals that a small but significant proportion of these patients are salvageable with agressive re-treatment.2’3’4*s Surgery or radiation have been used to treat these recurrences depending on their primary therapy. The results from different institutions vary depending on the re-treatment techniques and the distribution of patients in each series, and whether the recurrences are unifocal or multifocal, central or peripheral.6v7.‘0*” Favor-
November 1981, Volume 7, Number 1I
Fig. 5. Same patient at 8 year follow-up.
able response in 7 out of 44 patients re-treated for central recurrence was observed by Murphy & Schmitz.’ In the early 1970’s Barber et al.’ reported 263 patients who recurred after radiation therapy, or with persistence of cancer after radiation, who underwent pelvic exenterations and had a five year salvage of 12.8% (34 patients). Keetel et ~1.~ reported on 128 patients, re-treated with radiation therapy, who had a five year survival of 3.1%. In our series, 45% of the patients survived disease-free at one year and 10% survived without disease at 5 years or longer following interstitial implantation for recurrent cervical cancer. The optimal utilization of this procedure seems to depend on the site of recurrence, the extent of the disease in the pelvis and the status of para-aortic node involvement. This retrospective analysis enabled us to identify the prognostic factors (Figure 3). The most favorable group benefited by this technique were those who presented with either central recurrence or unilateral, localized pelvic side wall recurrent disease. Figures 4-7 show the isodose distribution in two patients in Group I who presented with unilateral pelvic side wall recurrence. The least morbidity was noticed in those patients with minimal surgical manipulations at the time of interstitial implantation. We recommend only limited
Recurrent gyncdogic cancer 0 D. NORIet 01.
Fig. 6. Thirty-four year old white female who presented with ca of the cervix, Stage HA, who underwent a radical hysterectomy and pelvic node dissection in 1975. This patient presented with a 4 x 4 x 3 cm pelvic side wall recurrence, one year after sugery, treated by permanent I-l 25 interstitial implantation. and essential surgical procedure should accompany interstitial implantation, since the associated morbidity and mortality is high and survival brief. Symptomatic relief can be obtained in nearly two-thirds of the patients presenting with symptoms. We believe re-irradiation with interstitial implantation is well tolerated and can be used to treat vaginal, cervical and periurethral recurrences. It
Fig. 7. Same patient NED at 5 year follow-up.
also can be recommended in patients who cannot be re-treated with further external radiation and in those who present with post-surgical pelvic side wall recurrences, where exenterative surgery is contraindicated and conventional external beam radiation cannot always control the disease effectively. In our experience, this technique is well tolerated with acceptable morbidity.
REFERENCES I. Barber, H.R.K., Brunschuig, A., Lewis, G.C., Jr., Wentz, W.B., Jaffee, R.F. (Eds.): Newer Concepts in Gynecological Oncology. Philadelphia, F.A. Davis, Co. 1966. 2. Calkins, L.A.: Re-treatment of carcinoma South M.J. 41: 902-906, 1948.
7.
of the cervix.
3. Evans, S.R., Jr., Hilaris, B.S., Barber, H.R.K.: External vs interstitial irradiation in unresectable recurrent cancer of the cervix. Cancer 28: 1284-l 288, 197 1. 4. Gary, R.K., Sala, J.M., Spratt, J.S.: The detection and treatment of post irradiationally recidivated cancers of the cervix uteri. Radiology 83: 208-2 18, 1964. 5. Graham, J.B., Hendrick, G.: Carcinoma of the cervix. Surg. Obstet. Gynecol. 105: 482-490, 1957. 6. Holt, G., Hilaris, B.S., Balter, S., Ragazzoni, G.D., Phillips, R.F., Laughlin, J.S.: Experience with computerized
8.
9. IO.
11.
implant dosimetry. Am. J. Roentgenol. 102: 688-193, 1968. Jones, Thomas K., Jr., Levitt, S.H., King, E.R.: Retreatment of carcinoma of the cervix with radiation. Radiology 95: 167-l 74, 1970. Keettel, W.C., Van Voorhis, L.W., Lortourvette, H.B.: Management of recurrent cancer of the cervix. Am. J. Obstet. Gynecol. 102: 671-679, 1968. Murphy, W.T., Schmitz, A.: Results of re-irradiation in cancer of the cervix. Radiology 67: 378-385, 1956. Prasasvinichai, S., Glassburn, J.R., Brady, L.W.: Treatment of recurrent carcinoma of the cervix. IN. J. Radiat. Oncol. Biol. Phys. 4: 957-961, 1978. Van Herik, M., Fricke, R.E.: Results of radiation therapy for recurrent cancer of the cervix uteri. Am. J. Roentgenof. 73: 437-440,1955.
03s(r3016/S1/111513~5~2.~/0 Copyrisht 0 1981 Pngamon Press Ltd.
??Original Contribution INTERSTITIAL IRRADIATION IN RECURRENT GYNECOLOGICAL CANCER D. NORI, M.D.,* B.S. HILARIS, M.D.,* H.S. KIM, M.D.,* D.G. CLARK, M.D.,? W.S.
KIM, M.D.,7
W.B.
Memorial Sloan-Kettering
JONES, M.D.?
AND J.L.
LEWIS JR.,
M.D.?
Cancer Center, 1275 York Ave., New York, NY 10021
Ninety-six patients with recurrent gynecological, cancer documented by biopsy underwent interstitial implantation at Memorial Sloan-Kettering Cancer Center during the period of 1957-1976. They are divided into two groups: Group I includes 75 patients with recurrent cervical cancer and Group If includes 21 patients with otber recurrent gynecological cancer. In Group I, 63 % (47) had previously received a full course of both external and intracavitary radiation, 22 % (17) had surgery and 12 % (9) had both sugery and radiation as prior management for their primary disease. In two patients, the prior management was not clearly documented. Symptomatic relief was obtained in 70% of the patients who initially presented with symptoms. Without subsequent treatment, 34 of these 75 (45%) patients were alive and disease-free at one year, 15 (20 % ) at two years, 12 (16 56) at three years, 9 (12 96) at four years and 7 (10% ) at five years. In Group If,48 %I (10) were alive and disease free at one year, 33 % (7) at two years, 24 % (5) at three years, 19 % (4) at four years and 5 % (1) at five years. Interstitial implant, Gynecological cancer, Radioiostopes.
patients) and with other primary urethra and ureter) (5 patients).
INTRODUCTION Interstitial implantation of radioactive materials is useful in the management of localized cancer. This technique allows the delivery of a much higher dose to the tumor
cancers
(vagina,
Group I (recurrent cancer of the cervix) Ninety-eight percent of the patients in this group had an epidermoid carcinoma; one patient had an adenocarcinoma. The median age was 55 years; the range was 21-70 years. Table 1 shows the stage at the initial diagnosis; 49% of the patients had Stage I & II carcinoma of the cervix. In 29 patients the initial stage was not available, as these patients were initially seen elsewhere. Forty-seven of the 75 patients (63%) were initially treated by radiation. This consisted of external beam therapy (2 patients), intracavitary irradiation (5 patients) and a combination of the two (40 patients). Surgery was used in the intitial management in 17 patients (22%). Surgery and radiation was used in 9 patients (12%). In the remaining 2 patients (3%), the type of previous treatment was not clearly documented. In 18 patients (24%), the recurrence was diagnosed within 6 months after the initial treatment. Seventy percent of all recurrences were observed within the first two years after initial treatment. Table 2 shows symptoms and signs observed at the time of recurrence. Pain (abdominal, pelvic and/or leg) was the most frequently mentioned symptom by these patients (80%). Swelling of lower extremities, vaginal
than is possible with external radiation, and gives a lower dose to the adjoining normal tissues. It is possible to use this technique in selected cases of recurrent gynecological cancer, recurring locally after a full course of external radiation, intracavitary radiation, surgery or a combination of these. Interstitial irradiation has been used at Memorial Hospital as an alternative method of treatment in patients with unresectable recurrent gynecological malignancies. Our earlier experience with intersitial irradiation in cancer of the cervix was reported in 1971. This present review includes all patients with recurrent gynecological malignancies treated by interstitial irradiation in our institution during a 20 year period.
METHODS AND MATERIALS From 1957-1976, 96 patients with recurrent gynecological cancers documented by biopsy underwent interstitial implantation. They are divided into two groups. Group I consists of 75 patients with recurrent cervical cancer and Group II consists of 21 patients with various other recurrent gynecological cancers from endometrial primary (7 patients), ovarian (6 patients), vulvar (3
Service, Department of Radiation Therapy. tGynecology Service, Department of Surgery.
Reprint request to: D. Nori, M.D. Accepted for publication 9 July 198 1.
*Brachytherapy
1513
Radiation Oncology 0 Biology 0 Physics
1514 Table
November 1981, Volume 7, Number I 1
1. Interstitial irradiation in recurrent gynecological cancer (Group
No.
No. of patients
Percent
II III IV
I3 23 6 4
I8 31 8 5
Unknown
29
38
Initial stage of disease Stage Stage Stage Stage
I
Table 3. Interstitial irradiation in recurrent gynecological cancer
I)
Unilateral pelvic side walls Pelvic side wall, para aortic and/or parametriae Vaginal Bilateral pelvic side walls Pelvic side wall and vagina Perineal
and/or rectal bleeding and palpable abdominal were less frequently observed. Twelve patients asymptomatic and the diagnosis of recurrence was on routine follow-up examination. Management. A histological confirmation of the rence was obtained prior to interstitial implantation 75 patients.
Sixty
of these
patients
underwent
mass were made recurin all
an explor-
in order to determine the extent of the disease. In the remaining 15 patients, the diagnosis was obtained by direct punch biopsy of the accessible tumor in the vagina or the perineum. Thirty-three of the 60 patients who underwent an exploratory laparotomy had disease limited to the pelvis (one or both side walls); the remaining 27 patients had para-aortic nodal involvement as well. Table 3 lists the site of implantation in all 75 patients. An attempt was made to implant all of the disease; however, this was not always possible when the disease had extended outside the pelvis to involve the para-aortic nodes. During this period different radioiostopes were used for interstitial implantation such as Iridium- 192, Radon222. Au- 198 and Iodine- 125. Permanent intersitial implants were favored and only occasional temporary implants were performed; Ir- 192 was used in 39 patients, (30 permanent and 9 temporary implants); Rn-222 in 12 patients, Au-l 98 in 1 patient, and more recently, I- 125 in 23 patients. The dose ranged from 20,000-30,000 rad if Iridium seeds were used or approximately half of this atory
laparotomy,
which
was performed
patients
Percent
32
43
17 13 7 4 2
23 I7 9 5 3
dose if Gold and Radon were used. When Iridium-192 was used for removable implant, the dose was prescribed at 0.5 cm from the plane of the implant and the total dose ranged from 4000-5000 rad in 4-5 days. Computer calculated isodose curves were obtained routinely at various planes in the last 10 years using the Memorial Hospital Computer Brachy Program. The MPD (minimal peripheral dose) with I-125 varied from 130-160 Gy. Partial resection of the tumor was performed in 17/75 patients (23%). In addition to interstitial implantation, various surgical procedures such as abdominal hysterectomy, bowel resection and transvesicle ureteroneocystomies for totally obstructed ureters were performed. Post-operative external pelvic radiation (4OOCL5000 rad in 4-4’/2 weeks) was given to 7 patients, either because all of the disease was not implanted, or because the dose distribution resulting from the implant was considered unsatisfactory. Mortality and morbidity. Four patients (5.3%) died
INTERSTITIAL IRRADIATION IN RECURRENT 6INECOlOOlCAL CANCER
Table 2. Interstitial
irradiation in recurrent gynecological cancer presenting signs and symptoms No. patients
Pain (pelvic) Pain and swelling of leg R.E. & asymptomatic Pain and abnormal I.V.P. Abnormal I.V.P. Vaginal bleeding Rectal bleeding Abdominal mass R.E. gram.
= Routine
examination;
Percent
36175 16115
12175 6175 6175 5175 3175 l/75 I.V.P.
= Intravenous
48 21 I6 8 8 6 4
1 pyelo-
1
2
3
4
5
6
Survival Post Implant (yrs)
Fig. 1. Survival tion.
of patients
treated
with interstitial
implanta-
7
Recurrent gynecologic cancer 0 D. NORIet ul.
INTERSTITIAL IRRADIATION IN RECURRENT 6YNECOLO6ICAL CANCER loo 80
Negative para-aortic Positive para-aortic
---
60 \ m \
20% u Z E lo8g $ 6g
-\ \
-----
(27)
I
I
I
I
I
t
1
2
3
4
5
Survival
within 30 days after laparotomy and implantation. In 3 patients, death was caused by pulmonary embolism; the fourth patient died of septicemia following evisceration. All post-operative deaths occurred in patients treated prior to 1967. Early complications (within the first 30 days) were observed in 10 other patients as follows: Thrombophlebitis of the lower extremities in 2 patients; perineal cellulitis in 2; urinary incontinence in 1 patient, urinary tract infection in 1 patient; and fever of unknown etiology in 4
Table 4. Survival in group II Survival
site
Endometrium Ovary Vulva Other (vagina, urethra, ureter) Total
patients. All of these reactions were transient and subsided after conservative management within 4 weeks. Late complications were observed in 5 patients as follows: Partial bowel obstruction in 2 patients; rectovaginal fistula in 1 patient; and radiation proctitis in 2 patients. These complications required surgical intervention in all 5 patients. Survival. Thirty-four of the 75 patients (45%) were alive and disease-free one year after implantation; and seven patients (10%) were alive and disease-free at 5 years after treatment. The median survival was 11 months. Patients with disease limited to the vagina, cervix or periurethral region had a better median survival (18 months) and 5 year survival (3 1%) (Figure 1). Figure 2 shows the survival rate for the 60 patients who underwent a laparotomy; 27 were found to have metastatic cervical carcinoma in the para-aortic nodes. The median survival was 6 months with involvement of the para-aortic nodes, and 18 months without, respectively. The 5 year survival in patients with positive nodes was 3% and 7% for the patients with negative nodes. Pain relief was obtained in 36/52 patients (70%) who had extensive pelvic side wall involvement that caused pain associated with evidence of the lower extremities swelling. The swelling itself was improved in 44% (7/ 16). Vaginal or rectal bleeding was improved in all 8 patients who presented with this symptom.
Post Implant (yrs)
Fig. 2. Survival data in patients with positive and negative para-aortic nodes.
Primary
1515
No. of patients
Median (months)
Range (months)
I 6 3
18 9.5 12
(O-61) (o-38) (o-36)
5
30
(7-48)
21
11
O-61 months
Group II (other recurrent gynecological cancers) This group consists of 21 patients with recurrent noncervical gynecological cancers with primary endometrial carcinomas (7 patients), ovarian (6 patients), vulvar (3 patients), vagina, and others (5 patients). Prior management included surgery and radiation in 14 patients (62%); surgery alone in 5 patients (24%) and radiation alone in 2 patients (4%). Iridium 192 was used in 6 patients and Iodine 125 in 15 patients. The implanted sites were as follows: vulva (1 patient), vagina (5 patients), pelvis (14 patients) and abdomen (I patient). No post-operative deaths occurred in this group. Table 4 shows the survival (median and range) in the
INTERSTITIAL IRRADIATION IN RECURRENT GYNECOLOGICAL CANCER Suggested Prognostic Factors Favorable:
1) Asymptomatic recurrence detected routine examination 2) Vaginal recurrences 3) Unilateral pelvic side wall involvement
Unfavorable:
1) Pelvic pain with leg edema 2) Multiple sites of recurrence in the pelvis 3) Positive para aortic nodes Fig. 3. Suggested
prognostic
factors.
1516
Radiation Oncology 0 Biology 0 Physics
Fig. 4. Fifty-five year-old white female who presented with ca of the cervix, Stage IIA, who underwent a radical hysterectomy and pelvic node dissection in 1970. This patient presented with a 5 x 5 x 4 cm pelvic side wall recurence, treated by permanent I-l 25 interstitial implantation.
of this group. The overall median survival was 11 months; one patient has survived over 5 years at last follow-up and was free of disease.
21 patients
DISCUSSION Recurrent cancer at any site spells gloomy prognosis. Cancer of the cervix that recurs after radical surgery or curative radiation therapy is a perplexing problem confronting both Gynecological & Radiation Oncologists. In many centers, oncologists are not enthusiastic to re-treat these patients, as they consider re-treatment futile. A review of the literature, however, reveals that a small but significant proportion of these patients are salvageable with agressive re-treatment.2’3’4*s Surgery or radiation have been used to treat these recurrences depending on their primary therapy. The results from different institutions vary depending on the re-treatment techniques and the distribution of patients in each series, and whether the recurrences are unifocal or multifocal, central or peripheral.6v7.‘0*” Favor-
November 1981, Volume 7, Number 1I
Fig. 5. Same patient at 8 year follow-up.
able response in 7 out of 44 patients re-treated for central recurrence was observed by Murphy & Schmitz.’ In the early 1970’s Barber et al.’ reported 263 patients who recurred after radiation therapy, or with persistence of cancer after radiation, who underwent pelvic exenterations and had a five year salvage of 12.8% (34 patients). Keetel et ~1.~ reported on 128 patients, re-treated with radiation therapy, who had a five year survival of 3.1%. In our series, 45% of the patients survived disease-free at one year and 10% survived without disease at 5 years or longer following interstitial implantation for recurrent cervical cancer. The optimal utilization of this procedure seems to depend on the site of recurrence, the extent of the disease in the pelvis and the status of para-aortic node involvement. This retrospective analysis enabled us to identify the prognostic factors (Figure 3). The most favorable group benefited by this technique were those who presented with either central recurrence or unilateral, localized pelvic side wall recurrent disease. Figures 4-7 show the isodose distribution in two patients in Group I who presented with unilateral pelvic side wall recurrence. The least morbidity was noticed in those patients with minimal surgical manipulations at the time of interstitial implantation. We recommend only limited
Recurrent gyncdogic cancer 0 D. NORIet 01.
Fig. 6. Thirty-four year old white female who presented with ca of the cervix, Stage HA, who underwent a radical hysterectomy and pelvic node dissection in 1975. This patient presented with a 4 x 4 x 3 cm pelvic side wall recurrence, one year after sugery, treated by permanent I-l 25 interstitial implantation. and essential surgical procedure should accompany interstitial implantation, since the associated morbidity and mortality is high and survival brief. Symptomatic relief can be obtained in nearly two-thirds of the patients presenting with symptoms. We believe re-irradiation with interstitial implantation is well tolerated and can be used to treat vaginal, cervical and periurethral recurrences. It
Fig. 7. Same patient NED at 5 year follow-up.
also can be recommended in patients who cannot be re-treated with further external radiation and in those who present with post-surgical pelvic side wall recurrences, where exenterative surgery is contraindicated and conventional external beam radiation cannot always control the disease effectively. In our experience, this technique is well tolerated with acceptable morbidity.
REFERENCES I. Barber, H.R.K., Brunschuig, A., Lewis, G.C., Jr., Wentz, W.B., Jaffee, R.F. (Eds.): Newer Concepts in Gynecological Oncology. Philadelphia, F.A. Davis, Co. 1966. 2. Calkins, L.A.: Re-treatment of carcinoma South M.J. 41: 902-906, 1948.
7.
of the cervix.
3. Evans, S.R., Jr., Hilaris, B.S., Barber, H.R.K.: External vs interstitial irradiation in unresectable recurrent cancer of the cervix. Cancer 28: 1284-l 288, 197 1. 4. Gary, R.K., Sala, J.M., Spratt, J.S.: The detection and treatment of post irradiationally recidivated cancers of the cervix uteri. Radiology 83: 208-2 18, 1964. 5. Graham, J.B., Hendrick, G.: Carcinoma of the cervix. Surg. Obstet. Gynecol. 105: 482-490, 1957. 6. Holt, G., Hilaris, B.S., Balter, S., Ragazzoni, G.D., Phillips, R.F., Laughlin, J.S.: Experience with computerized
8.
9. IO.
11.
implant dosimetry. Am. J. Roentgenol. 102: 688-193, 1968. Jones, Thomas K., Jr., Levitt, S.H., King, E.R.: Retreatment of carcinoma of the cervix with radiation. Radiology 95: 167-l 74, 1970. Keettel, W.C., Van Voorhis, L.W., Lortourvette, H.B.: Management of recurrent cancer of the cervix. Am. J. Obstet. Gynecol. 102: 671-679, 1968. Murphy, W.T., Schmitz, A.: Results of re-irradiation in cancer of the cervix. Radiology 67: 378-385, 1956. Prasasvinichai, S., Glassburn, J.R., Brady, L.W.: Treatment of recurrent carcinoma of the cervix. IN. J. Radiat. Oncol. Biol. Phys. 4: 957-961, 1978. Van Herik, M., Fricke, R.E.: Results of radiation therapy for recurrent cancer of the cervix uteri. Am. J. Roentgenof. 73: 437-440,1955.