Cancer of the ovary

Cancer of the ovary Survival

studies

chemotherapy,

ROY

T.

upon operative

H.

GEORGE

D. North

therapy,

and radiotherapy

PARKER,

CHARLES

Durham,

based

M.D. PARKER,

M.D.

WILBANKS,

M.D.

Carolina

The clinical characteristics, therapy, and results are reported on 262 patients who had primary ovarian cancer. Twenty-four per cent were Stage I and serous cystadenocarcinoma was the most frequent diagnosis (55 per cent). Only 30 per cent of patients had total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. The complete operation enhanced long-term survival in Stage I patients. Forty-four Qer cent of patients had an objective response to chemotherapy, while 31 per cent had a similar resQonse to radiotheraQy. Advanced ovarian cancer was present in 76 per cent of patients. Radiotherapy was given in localized advanced disease, and 73 per cent of patients received palliation. Chemotherapy was used in disseminated disease and provided palliation for 64 per cent of patients. Radiotherapy after operation enhanced the 2 year survival of patients with Stage IV disease. Chemotherapy did not seem to improve the survival of patients. Cumulative survival rates for patients with Stage I disease was 60 per cent at 5 years, and with Stage IV disease it was 20 Qer cent at 2 years and 6 Qer cent at five years.

Materials

A L T H 0 u G H T H E early diagnosis, treatment, and survival of patients with most gynecologic malignancies has greatly improved in the last half century, ovarian carcinoma patients continue to have a poor prognosis. The purpose of this paper is to review the experience of patients with ovarian carcinoma seen in Duke University Medical Center from 1951 through 1968. Patients have been evaluated for survival based upon clinical characteristics, extent of operation, and postoperative radiotherapy, chemotherapy, and a combination of both. From the Department pf 0.bstetrics and zrz;z;logy, Duke Unrversaty Medrcal Supported Foundation.

by the Stanley

and

methods

During this 18 year period, 346 patients were diagnosed as having ovarian carcinoma: 262 primary; 42 metastatic; 42 deleted. Forty-two patients who had secondary cancers of the ovaries are not included in the study. Of these forty-two patients with metastatic ovarian cancers, the primary was breast in 16, gastrointestinal tract in 13, endometrium in 11, malignant melanoma in 1, and lymphoblastic lymphoma in 1. Fortytwo other patients were eliminated because of inadequate therapy, insufficient information for proper evaluation, or questionable origin of the primary. The remaining 262 patients included in the study had a tissue diagnosis of primary ovarian carcinoma, accurate staging, and adequate follow-up. Survival times for analyses were calculated from the time of diagnosis to the date of death and, if living, to the time of last

Raczynski

Presented at the Ninety-third Annual Meeting of the American Gynecological Society, Hot Springs, Virginia, May 25-27, 1970. 878

Cancer

examination. Except for 19 patients, all living patients were followed through 1969. Those 19 patients lost to follow-up were considered as survivors only for the length of time to the last examination, even though only one had tumor when last seen. No discrimination was made between the patients dying of cancer and those dying of other causes, since only 8 patients died without evidence of cancer. The survival curves were calculated by plotting the percentage of patients remaining alive against the time interval from diagnosis. Clinical characteristics The race distribution was 201 Caucasians, 60 Negroes, and 1 Indian, Expected registration by color in the gynecology dinics is one to one. Of the 262 patients, 170 were seen on the private service and 92 on the resident service, which in part accounts for the Caucasian to Negro distribution. Table I shows the age distribution at the time of diagnosis. The mean age is 51 years. Eighty-four per cent of the patients were over 40 years of age and 67 per cent were over 50 years of age. Of the 131 patients for whom the menarchal age was known, the mean was 13 years. Ninety-seven patients (37 per cent) were menstruating, 151 (58 per cent) were postmenopausal, 1 patient was premenarchal, and in 13 patients the menstrual status was unknown. Seventy patients (27 per cent) had never conceived and 161 (62 per cent) had fewer than 3 pregnancies. These figures are not

Table I. Age distribution Aee

I

o- 10

Patients 1 4 13 23 73 67 60 21

11 - 20 21 - 30 31 - 40 31-50 51 -60 61 -70 71+ Total

at diagnosis

-

262

of ovwi

879

corrected for marriage and contraceptive practices. One hundred and eighty-nine patients (72 per cent) reported no abortion, only 15 (6 per cent) had more than two abortions, and none had five or more abortions. Sixty-seven patients (25 per cent) gave a family history of carcinoma. Seventeen patients had received previous pelvic irradiation for various reasons; 12 had received less than 2000 r and five more than 2000 r. Fifty-four patients had major gynccologic operations prior to developing ovarian carcinoma (Table II). Of the 77 patients who developed o\-arian carcinoma prior to the age of 45, 21 (27 per cent) had had a previous hysterectomy. Only 2 of the 21 patients had hysterectomy less than 5 years prior to developing cancer of the ovary and both were diagnosed within 2 years of operation. All 9 patients who had hysterectomy after age 45 developed ox,arian carcinoma 5 years or more after the hysterrctomy. Symptoms One hundred and forty-six patients (56 per cent j complained of pain, 1.21 (46 per cent) had abdominal swelling, and 80 (31 per cent) had a weight change of 10 pounds or more, usually weight loss. Fifty-eight patients (22 per cent) had abnormal bleeding, either a change in menstrual pattern or postmenopausal bleeding. Forty-seven patients ( 18 per cent) complained of pelvic pressure. Eighty-four patients (32 per cent) were asymptomatic when the diagnosis was made.

Table II. Previous Operative

gynecologic

procedure

operations Patients

Hysterectomy Less than 45 years Greater than 45 years Unilateral oophorectomy Ovarian cystectomy Tubal ligation Other None ___~-_--Total

-.----_._

___..~- ...__~ 26;: -

880

Parker,

Parker,

and

November 15, 197U Amer. J. Obstet. Gynec.

Wilbanks

Table III. Value the detection

of Papanicolaou of ovarian cancer

cytology

in

Table V. Operative

stage of disease

Stage Class

Patients

Per

cent

I II III IV V

38 108 2 4 12

23 66 1 2 8

Total

164

100

Patients

One ovary Two ovaries Pelvic viscera Outside pelvis, in bladder, or in rectum

I, II, III, IV, 11 Total

operative

Operation Total abdominal tomy, bilateral oophorectomy, Total abdominal tomy, bilateral oophorectomy Less than above Total

procedure 1 Patients

hysterecsalpingoomentectomy hysterecsalpingo-

Pathology

1 Per cent

78

30

58 126

22 48

262

100

The average duration of symptoms was 4 months. One hundred and seventy-three patients (75 per cent) had symptoms less than 6 months and 198 (85 per cent) had symptoms less than one year. On admission 71 patients (22 per cent) had a diagnosis of adnexal mass, either unilateral or bilateral, while 155 patients (59 per cent) were admitted with the diagnosis of abdominopelvic mass. Thirty-six patients (14 per cent) were diagnosed as having leiomyomata or other pelvic pathology. Seventy-eight patients (30 per cent) were felt to have ascites on admission. Prior to the diagnosis, Papanicolaou smears were done on 164 patients who were suitable to test the value of genital cytology in the detection of ovarian cancer. Patients with a previous hysterectomy or those with clinical vaginal metastases were not included in the evaluation. The results are shown in Table III. It can be seen that only 18 patients (11 per cent) had a suspicious or positive smear, Cul-de-sac aspirationl, 2 has not been used as a screening procedure in our clinic.

63 16 33

Per

cent

24

150 262

Table VI. Microscopic Table IV. Primary

(

100

diagnoses 1 Patients

1 Per cent

Serous cystadenocarcinoma Adenocarcinoma (solid) Pseudomucinous cystadenocarcinoma Undifferentiated carcinoma Malignant teratoma Granulosa-theta cell carcinoma Other

144 53

55 21

22 17 8

8 6 3

8 10

3 4

Total

262

Operative

100

treatment

All patients had celiotomy to make a tissue diagnosis and to treat primary ovarian carcinoma. The operative procedure of choice was total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy and/or removing as much tumor as possible. As shown in Table IV, only 78 patients (30 per cent) had the desired operative treatment. In others, the complete procedure was not technically possible, or the patients had been operated upon elsewhere and referred for further therapy. Table V shows the surgical staging of the extent of the disease according to the classification of Munnell and Taylor.3 The figures show the difficulty in making an early diagnosis of ovarian carcinoma as 150 patients (57 per cent) had Stage IV carcinoma when first evaluated, and 199 patients (76 per cent) had carcinoma which had spread beyond one ovary. The pathologic diagnoses are shown in Table VI. Even though the diagnosis of endometrioid carcinoma has been recognized

Cancer

in recent years, only one patient’s been diagnosed. Postoperative

tumor

has

therapy

Postoperatively, 144 patients received chemotherapy, 107 patients received radiotherapy, and 36 patients received both modes of treatment. Chemotherapy usually was given first because of the bone marrow suppression which followed irradiation. Radiotherapy was elected for those patients who had a pelvic mass but no disseminated disease, who failed to respond to chemotherapy, or who were referred directly to radiotherapy. The usual dosage was 4000 to 5000 r to the pelvis and 2000 r to the abdomen. Alkylating agents, primarily nitrogen mustard* and chlorambucil,+ have been used for chemotherapy.* Nitrogen mustard as a single injection was given intravenously in a dosage of 0.2 mg. per kilogram nightly for 2 days. This therapy was repeated approximately every 4 weeks depending upon the rapidity of bone marrow recovery, for a total of six courses. Those patients who had Stage IV disease and had shown a response to nitrogen mustard were then placed on chlorambucil orally. If it were felt that the patient could not tolerate the acute side effects of intra\.enous nitrogen mustard, chlorambucil was used orally. The starting dosage of chlorambucil was 9 to 14 mg. orally each morning before breakfast as a single dose and increasing or decreasing by 2 mg. increments as necessary to maintain a persistent leukopenia of 3.000 to 4zOO0 white blood cells per cubic millimeter range. In the absence of significant toxicity chlorambucil was continued daily at maintenance dosages as long as tumnr growth seemed to be controlled clinically, or tumor was not demonstrable for cm year. “Second look” operations were inirequcnt and performed only for specific indications. Other drugs used in a small number of patients included n,n’,n” ,-triethyIenethio-

Table VII.

Objective

of ovary

response __---_

Clinical To

evaluation

radiotherapy Increase in size No change in size* Decrease in size* Prophylactic use* Ko measurable lesion Cnknown Total

To

881

- ..^

Patients

11) 26 41 107

chemotherapy Increase in size Ko change in sizef Decrease in size+ Prophylactic use No measurable lesion Total

phosphoramide, cyclophosphamide, rnethotrexate, and AB-131 (an experimental alkylating agent), and one patient received Krcb&en without effect. Results Each patient receiving radiation or chemotherapy postoperatively was evaluated for objective and palliative responses. Only those patients with a palpable or radiographically measurable lesion were included in the utatistical analysis of objective response. Since thr patients who received both types of postoperative therapy did so at different times, it was possible to evaluate these patients for the response to each method separately. Stage I patients given prophylactic radiotherapy or chemotherapy were not analyzed. Likewise any patient with Stage II or more operative disease who did not have a lesion that could be clinically followed was deleted. For an objective response to be considered good, there had to be 50 per cent reduction in the size of a palpable tumor mass. a 50 per cent reduction in size of a radiographic lesion, or remission of ascites. The rc’sponsc had to last at least 6 months. Table VII shows the objective rctsponse to irradiation. Eleven patients (31 per crnt‘1 of the 36 patients for evaluation &owed a dccreasc or stabilization of the tumor

882

Parker, Parker, and Wilbanks Amer.

size for a period of 6 months or longer. The patients who received chemotherapy were evaluated in a similar manner. The objective response is also shown in Table VII. Thirty-nine (44 per cent) of 88 patients available for evaluation showed an objective response which is greater than that seen in radiotherapy. One hundred and ninety-nine patients (76 per cent) had advanced diseasewhen first seen and palliation became a major part of physician care. Therefore, all patients were evaluated for palliation according to the

Table VIII. Clinical To

Palliative response response

I

Patients

radiotherapy Poor Fair” Good* Prophylactic Unknown

21 9 47 26 4

Total To

I

77

107

chemotherapy Poor Fairt Goodt Prophylactic

43 20 57 24

Total

144

*corrected

response,

5B/rT or 73 per

tcorrected

response,

77/420 cm 64 per

cent. cent.

G 60 .z> 2 m 40

120

criteria of Parker and Shingleton4: ( 1) The patient was more comfortable, had lesspain, was able to resume a more normal pattern of living at home, and showed an improved mental attitude. (2) The ascites or pleural effusion diminished. (3) The massesdecreased in size. (4) The therapy did not produce complications worse than the disease. (5) The period of survival was 6 months or longer. Table VIII shows the palliation response to irradiation therapy. Fifty-six (73 per cent) of 77 patients available for evaluation were considered to have a fair to good response. Table VIII shows that 77 (64 per cent) of 120 patients for evaluation had a fair to good pahiative responseto chemotherapy. Patients with advanced Stage IV diseasenot suitable for radiotherapy were treated with chemotherapy and therefore were expected to have a poorer response. In an effort to evaluate survival by different modes of treatment, the patients were divided by stages. Stage II and Stage III groups did not include enough patients to allow a statistical analysis. Therefore only Stage I and Stage IV patients were evaluated for survival on a statistical basis. Stage I patients were evaluated for survival on the basisof operative procedure and the results are shown in Fig. 1. Twenty-one

6~0 and TAH ( 25 Patients) “*s-~u,,,,,,,,, Other (17 Patients I “““m’~-.~~... a.*.,. I,,,,,,,,((,0,,,, “.% 0SC,,,,, “.h,, ‘%,,“,,

20

Years After Fig. 1. Cumulative salpingo-oophorectomy;

November 15, 19X J. Obstet. Gynrc.

survival rate, TAH =

Diagnosis

Stage I. Operative procedures total abdominal hysterectomy.

and

survival.

BSO

=

Bilateral

Volume Number

Cancer of ovary

1Ml 6

patients had total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentcctomy, 25 patients had total abdominal hysterectomy and bilateral salpingo-oophorectomy without omentectomy, and 17 patients had a lesser procedure, usually a unilateral oophorectomy. In analyzing these data for survival at 2 years the p value was lessthan 0.05 when comparing those patients with total abdominal hysterectomy and bilateral salpingo-oophorectomy with or without omentectomy to those who had a lesser procedure. At 2 year follow-up omentectomy did not significantly affect the survival rate. At 5 year follow-up the p value for those patients having omentectomy with removal of the uterus, tubes, and ovaries was lessthan 0.025 when compared with the group who did not have omentectomy. This finding suggeststhat omentectomy may contribute to long-term survival, possibly because of the presence of microscopic metastases at the time of the operation. There is also a statistically significant difference in survival in the patients who had total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy as compared to those who had a procedure less than bilateral salpingo-oophorectomy and total abdominal hysterectomy. Also of interest is the lack of difference in survivai of those patients who

> 2 v)

had removal of the uterus, tubes, and ov~ies but no omentectomy as compared to the group with a lesscomplete operation. Six patients with Stage I disease bad ascites present at operation and 57 did not. There was no significant difference in survival at 2 and 5 years, suggesting that the presence of ascites is not an ominous sign as generally considered.” The survival c~u-ws are shown in Fig. 2. All Stage I patients were evaluated to determine if the capsule status at the time of operation had an effect on long-term survival. The capsule was noted to be removed intact, intact but ruptured at ol~ration, adherent to the viscera, or showinS excrescences.Survival curves are shown in Fig. 3. There was no statistically significant tiifl’erence between any two of the categories. Although the curve of the patients with excrescenceson the ovary declined sbxply, there were too few patients to he evablatcd adequately. Fig. 4 shows the survival curves of Stage I patients treated with operation only and operation followed by chemotherapy and/or radiotherapy. Although there appears to be a trend which suggeststhat those patients not receiving any postoperative treatment do not do as well, there is no statistically significant difference in survival at 2 and 5 years Ivhich

-.. --., _NlJ:cites (57 Patients 1 ---mm ---mm----.

40-

11I I 3I I II

0

5

883

lllll

7 9 II Years After Diagnosis

Fig. 2. Cumulativesurvival rate, StageI. Ascitesand survival.

III

13

ILL

15

Ii

884 Parker, Parker, and Wilbanks

November

Amer. J, Ohsrrt.

\ \

0

III I

2

Fig. 3. Cumulative

II 0

I

Fig. 4. Cumulative

3

\ \

%toct (27patients) 1-,111.11111111-11~-lllllll *Adherent to Viscera(6patients 1, Excrescences (3patients) \

II 4

survival

II 6

5

rate,

Stage

I

I

I

It

2

3

4

5

rate,

Stage

survival

15: 197~1 Gynec.

IIll 7 8 9 IO II Years after Diagnosis I. Condition

1

I

of ovarian

I

11

6 7 8 9 IO II Years after Diagnosis I. Postoperative

might support any particular method of therapy. There are not enough patients available for a 10 year follow-up to evaluate a difference. It appears in Fig. 1 that the extent or “adequacy” of operation as opposed to any postoperative therapy is the biggest factor in long-term survival in Stage I lesions. The over-all Stage I cumulative survival was 77 per cent at 2 years and 60 per cent

I I2

l r I 13 14 I5

capsule

1

I I 16 17

at time

11

of operation.

11

I2 13 I4 I5

I6

1

I7

therapy

5 years (Table IX). The importance of early diagnosis in survival is apparent.’ Patients with Stage IV disease were evaluated in a similar manner as that for Sage I patients. Fig. 5 shows survival curves based

at

on

initial

surgery.

Fifty-six

patients

had

total

abdominal hysterectomy, bilateral salpingooophorectomy, and omentectomy, 7 patients had total abdominal hysterectomy and bi-

Volume

of ovary

Cancer

1~111

Jc BSOondTAH

885

(7potientsl

Years after Diagnosis Fig. 5. Cumulative oophorectomy;

TAH

survival rate. Operative procedures = total abdominal hysterectomy.

BSO = Bilateral

and survival.

salpiwl

or Resected (9 patients)

0

I

2

3

Fig. 6. Cumulative survival Unknown in 5 patients.

4

5 rate,

6 Stage

7 8 9 IO II Years after Diagnosis IV.

lateral salpingo-oophorectomy without omentectomy, and 87 patients had a lesser procedure, usually celiotomy and biopsy. The extent of operations in Stage IV patients appears to have no effect on outcome, as there is no significant difference in survival at 2 years. At 5 years of follow-up there are

Survival

based

12 13 upon

extent

Table IX. Cumulative Stages I and IV

Stage I IV

___

I 14

I 15

I 16

of tumor

I 17 resected

survival

2 years (%) 77 20

over-:, 11

) I -.---

5 ysarr (T
886 Parker, Parker, and Wilbanks

Years After Diagnosis Fig. 7. Cumulative

survival rate, Stage IV. Ascites and survival.

A.= Radiotherapy (25 patients) B = Chemotheraov Ml oatients) C c Chemotheroov and Radiotherapy (21 patients) 6 = None (23 patients) E = Overall (150patients)

0

I

Fig. 8. Cumulative

2

I I I I W% ‘.I 7 8 9 10 II I2 Years after Diagnosis survival rate, Stage IV. Postoperative therapy 3

4

5

I 6

too few survivors to make any valid conclusions. In contrast to Stage I disease in which omentectomy appeared to improve 5 year survival, omentectomy did not improve survival in Stage IV disease. Fig. 6 suggests that removal of all gross tumor does appear to have a short-term beneficial effect. Nine patients had all apparent tumor removed and 136 patients did not. In 5 patients it was impossible to determine from the operative

I 13

I I4

I I5

I

I

16

I7

note if the tumor had been totally removed. Although the figures for total tumor removal are small, there is a statistically better survival at a 2 year follow-up for this group. At five years again the numbers are small and no statistical difference is seen. The patients with Stage IV disease were evaluated for the effect of the presence or absence of ascites on survival. Eighty-eight patients had ascites at initial operation and 62 did not. As was true in patients with

Cancer

Stage I disease, no significant difference was seen at 2 and 5 year follow-up between the two groups. The survival curves are shown in Fig. 7. Fig. 8 depicts the survival curves for the various modes of therapy. Twenty-three patients received no postoperative therapy, 25 received radiation therapy, 8 1 received chemotherapy, and 21 were given both radiotherapy and chemotherapy postoperatively. At a 2 year follow-up level there is significantly better survival for those patients who received radiotherapy as compared to those who received chemotherapy. The p value was less than 0.001. Likewise the p value in comparing the radiotherapy group to those with no postoperative therapy is significant with the p value of 0.01. There is no difference in survival in the radiotherapy group compared to those who rereived combination therapy postoperatively, which suggests again that chemotherapy did not add to survival. This suggestion is further supported by the lack of significant difference in survival of patients receiving chemotherapy postoperatively as compared to those with no postoperative therapy. There is a significant difference in survival at two years for those patients receiving combination therapy postoperatively. In the group who received no therapy the p value was 0.05 and again this demonstrates the effect of radiation therapy. At 5 years of follow-up there are no survivors who received no postoperative therapy. The over-all Stage IV cumulative survival

REFERENCES

1. Graham, J. B., and Graham, R. M.: J. Obstet. Gynec. Brit. Comm. 74: 371, 1967. ?. McGowan, L., Stein, D. B., and Miller, W.: AMER. J. OBSTET. GYNEC. 96: 413, 1966. 3. Munnell, E. W., and Taylor, H. C., Jr.: AMER.

J. &+sTET.

GYNRC.

58:

943.

1!++9.

Discussion

I,. MONTGO~IERY, Philadelphia, Pennsylvania. I rise to ask Dr. Parker two questions. In the group of patients that he felt received some palliation from the radiation therDR.

THADDELW

of

ovaw

887

Table X. Causes of death Cause Cancer Unrelated causes Cancer present Cancer absent Chemotherapy, no tumor Postoperative Cancer present Cancer absent Unknown Total

/ Patients / Per cent 165 87.3 15 8.0 9 6 1 0.6 6 7.1 .-I 1 r) I .o 189

100

rate at two years is 19.5 per cent and at 5 yeass 5.8 per cent (Table IX). At the present time 189 of the 262 patients evaluated have died. All living patients have had at least a 1 year follow-up and all but 15 have had a 2 year follow-up. The causes of death are presented in Table X. As is evident 165 patients (87.? per cent) died of carcinoma, while an additional l-1 died with cancer present, five postoperatively and 9 of unrelated causes for a total OF 179 patients (95 per cent) dying with cancer. One patient died of a direct complication of chmlotherapy because of secondary leukopenia and overwhelming sepsis. This occurred more than a year after initial operation and no tumor was found at autopsy. This patient was receiving 16 to 18 mg. of chlorambucil daily. As a general rule l,j, mg. of chlorambucil a day usually is the upper limits of bone marrow tolerance, and in longterm treatment the dosage avcragcs 1 to 8 mg. per day.

4. Parker, R. T., and Shingleton, W. W: AMER. J. OBSTET. GYNEC. 83: 981, 1962. 5. Pomerance, W., Moltz, A., and Hall, J. E.: AMER. J. OBSTET. GYNEC. 96: 418, 1966. 6. Keetel, W. C., Fox, M. R., and Longnecker, D. S.: AMER. ,J. ORSTET. GYNEC. 04: 766, 19fi6. spy, does he feel that the dose of Z,OOO roentgcrls intraperitoneally had any effect. And among the patients who had therapy has there lxaen evidence of kidney damage or irradiation damage to the kidney?

888

Parker,

DR.

Parker,

PARKER

less is given nephritis will

and

Wilbanks

(Closing). If 2,000 roentgens or to the upper abdomen, radiation not occur. If higher doses are used,

one must shield the kidneys to prevent radiation nephritis. If you must shield the upper abdomen, we do not feel it is worthwhile to give radiotherapy. Occasionally, we will exceed this dosage for spot radiotherapy when there is a persistent mass known has shown I think

to be a tumor and when the patient good response to over-all therapy. Dr. Stone’s comments concerning a

method of evaluation responsiveness, whether it be with ultrasound or any technique that we could provide, would be valuable. Since September, 1966, we have treated 106 patients with trophoblastic disease; 54 of these had metastatic disease and 50 had nonmetastatic disease. Of these patients, one third of them would not have responded to therapy had it not been for a sophisticated biologic assay that would take them

Nebraska The Nebraska Frontier Hotel to the Secretary,

State

Obstetric

and

to the very low levels of gonadotropin output. If we had such an assay or such a method of evaluating ovarian tumors, we would probably obtain results that would approach those in patients with trophoblastic disease. So long as you are treating empirically, you must keep the patient’s life in mind, and you will not treat as dangerously as you would if you had some sophisticated system of appraisal. In regard to Dr. Stone’s question concerning the previous operations in these patients, please refer to Table II and discussion of operation. These concentrate diagnosis

data

Once operation should feasible.

the

diagnosis should be be performed In our opinion,

we

need to an early

is established definitive performed. Reoperation when necessary, if it is omentectomy should be

included.

Gynecologic

State Obstetric and Gynecologic in Las Vegas, Nevada, December W. H. Taylor, Jr., M.D.

clearly point out that our efforts on making of ovarian carcinoma.

Society

Meeting

Society meeting will 3, 4, 5, 1970. Inquiries

be held at the New may be addressed