- Email: [email protected]
Adenocarcinoma of the endometrium, stage II: Problems in definition and management
Inr J Rodiorron Oncology Biol 0 Pergamon Press Ltd. 1980.
Phys.. Vol. 6, pp. 887-890 Pnnted ,n the U.S.A
??Current Concepts in Cancer: Uterine Fundal Cancer II
ADENOCARCINOMA OF THE ENDOMETRIUM, STAGE II: PROBLEMS IN DEFINITION AND MANAGEMENT HYWEL MADOC-JONES, M.D., PH.D. Division of Radiation
Endometrial,
Oncology,
Carcinoma,
Mallinckrodt
Institute of Radiology, 63108
University,
St. Louis,
MO
Stage II, Surgery, Radiation.
INTRODUCTION
Problems in the dejnition of Stage II endometrial carcinoma
In most institutions
in the United States, once a patient with endometrial carcinoma is assigned to Stage II (corpus et collum, spread of disease from the body of the uterus to the cervix) most likely she will be treated with preoperative radiation (external plus intracavitary), followed by a simple hysterectomy approximately six weeks later.‘j,’ There are two reasons for giving external irradiation. External irradiation can give a more uniform dose distribution to the primary tumor than is possible with intracavitary radiation alone. In addition, endocervical involvement may be associated with a relatively high incidence of pelvic node involvement (20%-50%).2 If a patient is medically inoperable, usually she will be treated by radiation alone. Many reports in the literature compare the results of patients who were treated using the combined approach of radiation and surgery with those who were treated using radiation alone.‘.’ Frequently, the erroneous conclusion is drawn that the combined treatment is superior to radiation alone. This conclusion is not valid unless the two treatment groups are truly comparable; this is never the case when patients are selected for radiation only, because of associated medical problems. Thus, the question of whether preoperative radiation and surgery is more effective than radiation alone has never been resolved in a properly controlled trial. Another unresolved question in the managment of Stage II endometrial carcinoma patients is whether a subgroup of patients exist in whom involvement of the endocervix is minimal. In such a subgroup, the incidence of pelvic node involvement may be lower than that reported for the stage at large; in this subgroup it is possible that the use of external radiation is not warranted. Before either of these two questions can be considered, we must define exactly what we mean when we designate a patient as having Stage II endometrial carcinoma. Accepted
Washington
The definition of Stage II endometrial carcinoma is simple conceptually; it merely means that there is extension of the disease from the body of the uterus to the cervix. In practice, however, it is not nearly so simple. First, let us consider the difficulty sometimes encountered in determining whether disease began in the endometrium or in the endocervix (Figure 1). If adenocarcinoma is found just at the border of the lower uterine segment extending into the endocervix, the physician performing the curettage will label disease either as adenocarcinoma of the endocervix, extending up into the endometrium (FIG0 Stage I, adenocarcinoma of the endocervix)3 or as adenocarcinoma of the endometrium extending down into the endocervix (FIG0 Stage II, adenocarcinoma of the endometrium). In institutions where most patients with Stage I carcinoma of the cervix are treated by radiotherapy, the former assignment will commit the patient to a treatment using radiotherapy alone, whereas the latter assignment will usually commit the patient to a planned course of preoperative radiotherapy and hysterectomy. Thus, the same condition could be treated in two distinct ways merely depending upon how it is labeled in the first place. In addition, other subtleties must be considered. When the staging D and C is performed, biopsies of the exocervix and fractional curettage of the endocervix and endometrium also are performed. In addition, the physician inspects and palpates the cervix and assesses clinically whether it is involved grossly. If the physician notes gross involvement of the cervix, and microscopic examination of either the punch biopsy or of the endocervical curettage shows adenocarcinoma, then the patient’s disease clearly falls into Stage II. If the cervix is not involved clinically but microscopic examination shows adenocarcinoma in the endocervical curettings and the curettings contain glands that are identified as endocervi-
for publication 27 November 1979. 887
888
Radiation
ENDOMETRIAL
Oncology 0 Biology 0 Physics
CARCINOMA
I
Al I
UieI he Cavity
July 1980, Volume 6, Number
7
technique is used, a combination of 2000 rad to the whole pelvis, followed by 3000 rad to split fields at a daily dose rate of 180 rad is standard treatment.’ Whole pelvis external therapy is followed by a single intracavitary insertion for a total exposure of between 3000-5500 mg hours (details of treatment beyond the scope of this essay). Patients who are medically inoperable, are treated with radiation alone. The same amount of external radiation as described above is usually given and a second intracavitary insertion is added in place of the hysterectomy.
lntemof 0s
Results of treatment
Fig, 1. Diagram to illustrate the difficulty in sometimes distinguishing between carcinoma of the cervix extending upwards to the body of the uterus and carcinoma of the endometrium extending downward into the cervix.
cal glands showing invasion by the tumor, or if stromal invasion is demonstrated, then clearly, the patient would fall into Stage II also. However, sometimes endocervical glands may be identified but without containing tumor; only fragments of tumor can be seen interspersed with the normal-appearing endocervical glands. This usually is considered as resulting from “contamination from above.” Thus, finally it is the clinician and the pathologist who must decide whether the patient’s disease, should be considered Stage I or Stage II. The strictness of these definitions may vary from one institution to another or even within one institution over a period of time, thus making it very difficult to compare one series with another. It may also explain why the percentage of all endometrial cancer patients who are placed in Stage II may vary from g-2010, not only from one institution to another, but even within one institution over a period of time.2
The results of such treatment for this stage have been recently reviewed and reported from many institutions. ‘.2,5*6.7.9,‘ The o results at the Mallinckrodt Institution of Radiology (MIR), Washington University School of Medicine, St. Louis, will be presented, since they are readily available to the author and are quite typical of those in the literature.* At this institution, we reviewed retrospectively all case histories of patients with Stage II endometrial carcinoma who were treated from 1959 through 1975. 57 of nearly 500 total patients were treated definitively for this stage disease; they comprised 11% of the total. Twenty of these patients were treated with radiation only because they were medically inoperable. The remainder were treated with a combination of surgery and irradiation. Of this subgroup, ten patients were treated with intracavitary irradiation only (without any external radiation) followed by a hysterectomy. Figure 2 shows the survival curves for these two groups of patients. It is usual for patients who were treated with ENDOMETRIUM
STAGE
II
Present treatment policies For medically operable patients, preoperative radiation followed by surgery is the present treatment of choice (with the proviso given above). Treatment begins with external radiotherapy to the pelvis. If high energy photons (20-25 MeV) are available, patients may be treated simply through AP/PA parallel opposed portals. If lower energy supravoltage equipment is used, many radiotherapists will use a multiple field technique in order to spread the subcutaneous dose. At the M.D. Anderson Hospital, a patient would receive 4000 rad to the whole pelvis at a daily dose rate of 200 rad.4 In other institutions where a more complex step-wedge blocking
I 0
I
1
I
1
2
3
1
1
I
1
I
I
I
4
5
6
7
8
9
10
YEARS
Fig. 2. Actuarial survival curves for Stage 11 endometrial carcinoma treated at the Mallinckrodt Institute of Radiology comparing patients treated by radiation and surgery versus radiation alone (selected on grounds of medical inoperability).
Adenocarcinoma of the endometrium 0 H. MAD~C-JONES
irradiation and surgery to do somewhat better than patients treated by irradiation alone. However, the patients who were treated without surgery were selected because of age or serious medical problems that contraindicated surgery. The difference between the two survival curves in Figure 2 is significant (p = 0.01). However, one cannot draw the conclusion that the combined modality is necessarily superior to radiation alone. Other possible explanations are that the patients who were selected for radiotherapy alone because of medical problems were understaged, compared with the combined modality group; the natural history of Stage II disease may be different in patients who already are plagued with other medical problems. It would be necessary to conduct a properly randomized study on medically operable patients to determine whether the combined modality is superior to radiation alone. To my knowledge, this is not being done at this time. However, in a recent report’ Brady described the elective use of radiation alone to treat medically operable patients with Stage 11 disease; his preliminary results are most encouraging and suggest that radiation alone may be equal to the combined modality. The most striking finding of the MIR study pertained to the combined modality group. When the hysterectomy specimen was examined for residual disease approximately six weeks after pelvic radiation, half the patients had no residual disease. This finding is of great prognostic significance as Figure 3 shows. Although the numbers are small, the difference between the two groups, those with or without residual tumor, is highly significant (p = 0.02). None of the patients who had a negative hysterectomy specimen in this study died. A simple explanation of
ENDOMETRIUM Prognosis
0
from
1
Pothologicol
2
3
STAGE II
Findtngs
4
5
tn Hysterectomy
6
7
0
Speamens
9
IO
YEARS
Fig. 3. Prognostic significance of failure to find residual disease in the hysterectomy specimen after preoperative radiation (p = 0.02).
889
this finding is, that the group of patients with no residual disease had the smallest initial number of tumor cells prior to irradiation. Unless one can normalize for the initial cell number, one cannot make any deductions regarding the radioresponsiveness of the tumor. It was also found that there was no correlation between prognosis and size of the uterine cavity in Stage I I, which agrees with recent findings for Stage I disease. Moreover, there was no prognostic significance in the duration of symptoms or the age of the patient in relation to menopause. The subgroup of ten patients who were treated with an intracavitary insertion only followed by a hysterectomy is extremely interesting. They must have been selected for this limited treatment because of clinical findings of minimal disease at the time of diagnosis and staging. Nine of those ten patients are alive and well at this time. This would suggest that this subgroup of patients has a low incidence of pelvic node involvement. Discussion Because Stage II comprises a relatively small proportion of all endometrial carcinoma patients, the number of patients who are available for study in any one institution is small. Thus, it is difficult to answer questions regarding definitive clinical management except in multi-institution trials. Because Stage II is a small subgroup in the first place, it is difficult to divide it into further subgroups and thus, spare some patients external radiotherapy. However, it is quite possible that patients with a clinically negative cervix may well have a quite different natural history from that of patients with grossly involved cervix. In addition, the histopathological grade may be of great significance within Stage II but this has not been definitively shown because of the paucity of numbers. At Washington University, St. Louis, while most of the Stage II endometrial carcinoma patients wiII continue to be treated in the conventional manner by preoperative external radiation, intracavitary insertion and a hystcrectomy, we are considering the possibility of conducting a trial to see whether patients with clinically negative cervix, histopathological Grade I and II, could be treated equally well using a preoperative intracavitary insertion followed by hysterectomy in a matter of a few days, as is now done for many patients with Stage I disease. It may be possible to spare a subgroup of Stage II patients external radiotherapy. Conclusion I. The definition of Stage II endometrial carcinoma is conceptually simple but in practice it is extremely complex and makes it difficult to compare results from one institution to another or within one institution at different periods of time. 2. While preoperative irradiation followed by hysterectomy is the current treatment of choice for medically operable patients, it has never been proven in a properly
Radiation
890
Oncology
0 Biology
0 Physics
conducted trial that such a combined modality is necessarily superior to radiation alone. In fact, as Fig. 3 shows the results of treatment with radiation alone are remarkably good for patients who were selected because of poor prognostic factors. 3. There is probably a subgroup within Stage II of
July
1980, Volume
6, Number
7
patients with a clinically negative cervix and whose disease has a favorable histopathological grade. These patients might benefit from an intracavitary insertion without any external radiation, followed by hysterectomy. We are proposing a study of this possibility in our own institution.
REFERENCES I. Brackman,
J.E.,
Goodman, R.L., Murthy, A., Marck, A.:
Combined irradiation and surgery in the treatment of Stage I I carcinoma of the endometrium. Cancer 42: 1146-
1151, 1978. 2. Brady, L.W.: The management
of carcinoma involving the cervix and body of the uterus (Stage II), Chap. 7. In Endometrial Carcinoma and Its Treatment: The Role of Irradiation, Extent of Surgery and Approach to Chemotherapy, L.A. Gray, Sr., (Ed.).C.C. Thomas, Springfield, IL, 1977. 3. FIGO: Acta. Obstet. Gynecol. Stand. 50: I, 1971. 4. Fletcher, G.H.: Textbook of Radiotherapy, Lea and Febiger, Philadelphia, PA. 1973, p. 668. 5. Hernandez, W., Nolan, J.F., Morrow, C.P., Jernstrom, P.H.: Stage II. Endometrial carcinoma: Two modalities of treatment. Am. J. Obstet.,Gynecol. 131: 171-175, 1978.
6. Jones, H.W.: Treatment
of adenocarcinoma of the endometrium. Obstet. & Gynecol. 30: 147-169, 1975. 7. Kottmeier, H.L.: Recent experience of the radiumhemmet,
Stockholm,
Chap.
II.
Endometrial
Carcinoma
and Its
Treatment: The Role of Irradiation, Extent of Surgery and Approach to Chemotherapy, L.A. Gray, Sr., Ed. C.C. Thomas, Springfield, IL, 1977. 8. Madoc-Jones, H., Zivnuska, F., Perez, C.A., Galakatos, A., Kao, MS.: Analysis of treatment results in Stage II endometrial carcinoma. In preparation. E.A., Fowler, W.C., Rogoff, E.E., Jelofsek, F., 9. Surwit, Parker, R.T., Creasman, W.T.: Stage II carcinoma of the endometrium. Int. J. Radiat. Oncol. Biol. Phys. 5: 323326, 1979. IO. Tak, W.K.: Carcinoma of the endometrium with cervical involvement (Stage II). Cancer 43: 2504-2509, 1979.
Phys.. Vol. 6, pp. 887-890 Pnnted ,n the U.S.A
??Current Concepts in Cancer: Uterine Fundal Cancer II
ADENOCARCINOMA OF THE ENDOMETRIUM, STAGE II: PROBLEMS IN DEFINITION AND MANAGEMENT HYWEL MADOC-JONES, M.D., PH.D. Division of Radiation
Endometrial,
Oncology,
Carcinoma,
Mallinckrodt
Institute of Radiology, 63108
University,
St. Louis,
MO
Stage II, Surgery, Radiation.
INTRODUCTION
Problems in the dejnition of Stage II endometrial carcinoma
In most institutions
in the United States, once a patient with endometrial carcinoma is assigned to Stage II (corpus et collum, spread of disease from the body of the uterus to the cervix) most likely she will be treated with preoperative radiation (external plus intracavitary), followed by a simple hysterectomy approximately six weeks later.‘j,’ There are two reasons for giving external irradiation. External irradiation can give a more uniform dose distribution to the primary tumor than is possible with intracavitary radiation alone. In addition, endocervical involvement may be associated with a relatively high incidence of pelvic node involvement (20%-50%).2 If a patient is medically inoperable, usually she will be treated by radiation alone. Many reports in the literature compare the results of patients who were treated using the combined approach of radiation and surgery with those who were treated using radiation alone.‘.’ Frequently, the erroneous conclusion is drawn that the combined treatment is superior to radiation alone. This conclusion is not valid unless the two treatment groups are truly comparable; this is never the case when patients are selected for radiation only, because of associated medical problems. Thus, the question of whether preoperative radiation and surgery is more effective than radiation alone has never been resolved in a properly controlled trial. Another unresolved question in the managment of Stage II endometrial carcinoma patients is whether a subgroup of patients exist in whom involvement of the endocervix is minimal. In such a subgroup, the incidence of pelvic node involvement may be lower than that reported for the stage at large; in this subgroup it is possible that the use of external radiation is not warranted. Before either of these two questions can be considered, we must define exactly what we mean when we designate a patient as having Stage II endometrial carcinoma. Accepted
Washington
The definition of Stage II endometrial carcinoma is simple conceptually; it merely means that there is extension of the disease from the body of the uterus to the cervix. In practice, however, it is not nearly so simple. First, let us consider the difficulty sometimes encountered in determining whether disease began in the endometrium or in the endocervix (Figure 1). If adenocarcinoma is found just at the border of the lower uterine segment extending into the endocervix, the physician performing the curettage will label disease either as adenocarcinoma of the endocervix, extending up into the endometrium (FIG0 Stage I, adenocarcinoma of the endocervix)3 or as adenocarcinoma of the endometrium extending down into the endocervix (FIG0 Stage II, adenocarcinoma of the endometrium). In institutions where most patients with Stage I carcinoma of the cervix are treated by radiotherapy, the former assignment will commit the patient to a treatment using radiotherapy alone, whereas the latter assignment will usually commit the patient to a planned course of preoperative radiotherapy and hysterectomy. Thus, the same condition could be treated in two distinct ways merely depending upon how it is labeled in the first place. In addition, other subtleties must be considered. When the staging D and C is performed, biopsies of the exocervix and fractional curettage of the endocervix and endometrium also are performed. In addition, the physician inspects and palpates the cervix and assesses clinically whether it is involved grossly. If the physician notes gross involvement of the cervix, and microscopic examination of either the punch biopsy or of the endocervical curettage shows adenocarcinoma, then the patient’s disease clearly falls into Stage II. If the cervix is not involved clinically but microscopic examination shows adenocarcinoma in the endocervical curettings and the curettings contain glands that are identified as endocervi-
for publication 27 November 1979. 887
888
Radiation
ENDOMETRIAL
Oncology 0 Biology 0 Physics
CARCINOMA
I
Al I
UieI he Cavity
July 1980, Volume 6, Number
7
technique is used, a combination of 2000 rad to the whole pelvis, followed by 3000 rad to split fields at a daily dose rate of 180 rad is standard treatment.’ Whole pelvis external therapy is followed by a single intracavitary insertion for a total exposure of between 3000-5500 mg hours (details of treatment beyond the scope of this essay). Patients who are medically inoperable, are treated with radiation alone. The same amount of external radiation as described above is usually given and a second intracavitary insertion is added in place of the hysterectomy.
lntemof 0s
Results of treatment
Fig, 1. Diagram to illustrate the difficulty in sometimes distinguishing between carcinoma of the cervix extending upwards to the body of the uterus and carcinoma of the endometrium extending downward into the cervix.
cal glands showing invasion by the tumor, or if stromal invasion is demonstrated, then clearly, the patient would fall into Stage II also. However, sometimes endocervical glands may be identified but without containing tumor; only fragments of tumor can be seen interspersed with the normal-appearing endocervical glands. This usually is considered as resulting from “contamination from above.” Thus, finally it is the clinician and the pathologist who must decide whether the patient’s disease, should be considered Stage I or Stage II. The strictness of these definitions may vary from one institution to another or even within one institution over a period of time, thus making it very difficult to compare one series with another. It may also explain why the percentage of all endometrial cancer patients who are placed in Stage II may vary from g-2010, not only from one institution to another, but even within one institution over a period of time.2
The results of such treatment for this stage have been recently reviewed and reported from many institutions. ‘.2,5*6.7.9,‘ The o results at the Mallinckrodt Institution of Radiology (MIR), Washington University School of Medicine, St. Louis, will be presented, since they are readily available to the author and are quite typical of those in the literature.* At this institution, we reviewed retrospectively all case histories of patients with Stage II endometrial carcinoma who were treated from 1959 through 1975. 57 of nearly 500 total patients were treated definitively for this stage disease; they comprised 11% of the total. Twenty of these patients were treated with radiation only because they were medically inoperable. The remainder were treated with a combination of surgery and irradiation. Of this subgroup, ten patients were treated with intracavitary irradiation only (without any external radiation) followed by a hysterectomy. Figure 2 shows the survival curves for these two groups of patients. It is usual for patients who were treated with ENDOMETRIUM
STAGE
II
Present treatment policies For medically operable patients, preoperative radiation followed by surgery is the present treatment of choice (with the proviso given above). Treatment begins with external radiotherapy to the pelvis. If high energy photons (20-25 MeV) are available, patients may be treated simply through AP/PA parallel opposed portals. If lower energy supravoltage equipment is used, many radiotherapists will use a multiple field technique in order to spread the subcutaneous dose. At the M.D. Anderson Hospital, a patient would receive 4000 rad to the whole pelvis at a daily dose rate of 200 rad.4 In other institutions where a more complex step-wedge blocking
I 0
I
1
I
1
2
3
1
1
I
1
I
I
I
4
5
6
7
8
9
10
YEARS
Fig. 2. Actuarial survival curves for Stage 11 endometrial carcinoma treated at the Mallinckrodt Institute of Radiology comparing patients treated by radiation and surgery versus radiation alone (selected on grounds of medical inoperability).
Adenocarcinoma of the endometrium 0 H. MAD~C-JONES
irradiation and surgery to do somewhat better than patients treated by irradiation alone. However, the patients who were treated without surgery were selected because of age or serious medical problems that contraindicated surgery. The difference between the two survival curves in Figure 2 is significant (p = 0.01). However, one cannot draw the conclusion that the combined modality is necessarily superior to radiation alone. Other possible explanations are that the patients who were selected for radiotherapy alone because of medical problems were understaged, compared with the combined modality group; the natural history of Stage II disease may be different in patients who already are plagued with other medical problems. It would be necessary to conduct a properly randomized study on medically operable patients to determine whether the combined modality is superior to radiation alone. To my knowledge, this is not being done at this time. However, in a recent report’ Brady described the elective use of radiation alone to treat medically operable patients with Stage 11 disease; his preliminary results are most encouraging and suggest that radiation alone may be equal to the combined modality. The most striking finding of the MIR study pertained to the combined modality group. When the hysterectomy specimen was examined for residual disease approximately six weeks after pelvic radiation, half the patients had no residual disease. This finding is of great prognostic significance as Figure 3 shows. Although the numbers are small, the difference between the two groups, those with or without residual tumor, is highly significant (p = 0.02). None of the patients who had a negative hysterectomy specimen in this study died. A simple explanation of
ENDOMETRIUM Prognosis
0
from
1
Pothologicol
2
3
STAGE II
Findtngs
4
5
tn Hysterectomy
6
7
0
Speamens
9
IO
YEARS
Fig. 3. Prognostic significance of failure to find residual disease in the hysterectomy specimen after preoperative radiation (p = 0.02).
889
this finding is, that the group of patients with no residual disease had the smallest initial number of tumor cells prior to irradiation. Unless one can normalize for the initial cell number, one cannot make any deductions regarding the radioresponsiveness of the tumor. It was also found that there was no correlation between prognosis and size of the uterine cavity in Stage I I, which agrees with recent findings for Stage I disease. Moreover, there was no prognostic significance in the duration of symptoms or the age of the patient in relation to menopause. The subgroup of ten patients who were treated with an intracavitary insertion only followed by a hysterectomy is extremely interesting. They must have been selected for this limited treatment because of clinical findings of minimal disease at the time of diagnosis and staging. Nine of those ten patients are alive and well at this time. This would suggest that this subgroup of patients has a low incidence of pelvic node involvement. Discussion Because Stage II comprises a relatively small proportion of all endometrial carcinoma patients, the number of patients who are available for study in any one institution is small. Thus, it is difficult to answer questions regarding definitive clinical management except in multi-institution trials. Because Stage II is a small subgroup in the first place, it is difficult to divide it into further subgroups and thus, spare some patients external radiotherapy. However, it is quite possible that patients with a clinically negative cervix may well have a quite different natural history from that of patients with grossly involved cervix. In addition, the histopathological grade may be of great significance within Stage II but this has not been definitively shown because of the paucity of numbers. At Washington University, St. Louis, while most of the Stage II endometrial carcinoma patients wiII continue to be treated in the conventional manner by preoperative external radiation, intracavitary insertion and a hystcrectomy, we are considering the possibility of conducting a trial to see whether patients with clinically negative cervix, histopathological Grade I and II, could be treated equally well using a preoperative intracavitary insertion followed by hysterectomy in a matter of a few days, as is now done for many patients with Stage I disease. It may be possible to spare a subgroup of Stage II patients external radiotherapy. Conclusion I. The definition of Stage II endometrial carcinoma is conceptually simple but in practice it is extremely complex and makes it difficult to compare results from one institution to another or within one institution at different periods of time. 2. While preoperative irradiation followed by hysterectomy is the current treatment of choice for medically operable patients, it has never been proven in a properly
Radiation
890
Oncology
0 Biology
0 Physics
conducted trial that such a combined modality is necessarily superior to radiation alone. In fact, as Fig. 3 shows the results of treatment with radiation alone are remarkably good for patients who were selected because of poor prognostic factors. 3. There is probably a subgroup within Stage II of
July
1980, Volume
6, Number
7
patients with a clinically negative cervix and whose disease has a favorable histopathological grade. These patients might benefit from an intracavitary insertion without any external radiation, followed by hysterectomy. We are proposing a study of this possibility in our own institution.
REFERENCES I. Brackman,
J.E.,
Goodman, R.L., Murthy, A., Marck, A.:
Combined irradiation and surgery in the treatment of Stage I I carcinoma of the endometrium. Cancer 42: 1146-
1151, 1978. 2. Brady, L.W.: The management
of carcinoma involving the cervix and body of the uterus (Stage II), Chap. 7. In Endometrial Carcinoma and Its Treatment: The Role of Irradiation, Extent of Surgery and Approach to Chemotherapy, L.A. Gray, Sr., (Ed.).C.C. Thomas, Springfield, IL, 1977. 3. FIGO: Acta. Obstet. Gynecol. Stand. 50: I, 1971. 4. Fletcher, G.H.: Textbook of Radiotherapy, Lea and Febiger, Philadelphia, PA. 1973, p. 668. 5. Hernandez, W., Nolan, J.F., Morrow, C.P., Jernstrom, P.H.: Stage II. Endometrial carcinoma: Two modalities of treatment. Am. J. Obstet.,Gynecol. 131: 171-175, 1978.
6. Jones, H.W.: Treatment
of adenocarcinoma of the endometrium. Obstet. & Gynecol. 30: 147-169, 1975. 7. Kottmeier, H.L.: Recent experience of the radiumhemmet,
Stockholm,
Chap.
II.
Endometrial
Carcinoma
and Its
Treatment: The Role of Irradiation, Extent of Surgery and Approach to Chemotherapy, L.A. Gray, Sr., Ed. C.C. Thomas, Springfield, IL, 1977. 8. Madoc-Jones, H., Zivnuska, F., Perez, C.A., Galakatos, A., Kao, MS.: Analysis of treatment results in Stage II endometrial carcinoma. In preparation. E.A., Fowler, W.C., Rogoff, E.E., Jelofsek, F., 9. Surwit, Parker, R.T., Creasman, W.T.: Stage II carcinoma of the endometrium. Int. J. Radiat. Oncol. Biol. Phys. 5: 323326, 1979. IO. Tak, W.K.: Carcinoma of the endometrium with cervical involvement (Stage II). Cancer 43: 2504-2509, 1979.