PROGNOSTIC FACTORS IN ADVANSED OVARIAN CANCER · chemotherapy, a second look operation, recurrence,...
Transcript of PROGNOSTIC FACTORS IN ADVANSED OVARIAN CANCER · chemotherapy, a second look operation, recurrence,...
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PROGNOSTIC FACTORS IN
ADVANSED OVARIAN CANCER
Dr. Hisham Rahahle Gynecologist, MD, Ph.D
Subspecialty in Gynecological Oncology
E-mail: [email protected]
mailto:[email protected]
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Abstract:
This study includes (68) patient diagnosed with advanced epithelial ovarian cancer in the years (1990-1995).
The aim of this study was to evaluate the effect on the survival rate in relation to the following factors: age, parity, number of abortions, surgically removable tumors, surgical findings, staging, histological types and grades of tumors, size of the residual tumors, chemotherapy, a second look operation, recurrence, metastasis and treatment.
According to FIGO staging of epithelial ovarian cancer, the results were:
56% had stage III, 44 % had stage IV.
All patients received adjuvant cytotoxic (I.V) cisplatin polychemotherapy after primary cytoreduction then a second-look laparotomy was performed.
Overall survival rate at five years was 26.15%.
Overall survival rate at ten years was 18%.
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Introduction
Incidence:
In the US approximately 25 000 new cases are diagnosed annually. Epithelial ovarian cancer is the 5th cause of death indicating that 1 in 70 women will develop ovarian cancer in her life time.
Age and Parity:
The highest incidence of ovarian cancers was in menopausal women between ages 60 – 65.
Parity: nulliparous rather than multiparous were more affected.
Breast Feeding:
Is a protective factor against ovarian cancer.
Menopause: More common in late menopause and early menarche
(Hildreth,cols,1981)(5)
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Clinical picture:
History:
Signs and symptoms:
-Abdominal distension.
-Abdominal discomfort.
-Flatulence.
-Change in the bowel motion.
On physical examination:
-A Pelvic mass was palpated
-Ascites was found
-Pleural effusion
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CONT..
Investigations:
-Complete blood analysis
-Urine analysis
-Coagulation profile
-Tumor markers CA-125
-chest X-ray
-ECG
-Extension studies
-Abdominal ultrasound
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Metastasis:
- Direct spread transcodomic through
peritoneal surface,
- Lymphatic metastasis mainly in advance
stage .(12,15)
- Hematogenous spread: Metastasis to
lung, liver, kidney and bone (Dauplat and
cols 1987) (16,17,18) .
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Staging of advanced epithelial ovarian
cancers according to FIGO(12) .
Stage
Criteria
Stage III Tumors involving one or both ovaries with peritoneal implants outside the
pelvis and/or positive retroperitoneal or inguinal lymph nodes. Superficial
metastases equals stage III. Tumor is limited to the true pelvis but with
histological proven malignant extension to small bowel or omentum.
Stage IIIa Tumor grossly limited to the true pelvis with negative lymph nodes but
with histological confirmed microscopic seeding of abdominal peritoneal
surfaces.
Stage IIIb Tumor of one or both ovaries with histologically confirmed implants of
abdominal peritoneal surfaces, non exceeding 2cm in diameter. Nodes are
negative.
Stage IIIc Abdominal implants greater than 2cm in diameter and/or positive
retroperitoneal or inguinal lymph nodes.
Stage IV Growth involving one or both ovaries with distant metastases. If pleural
effusion is present there must be positive cytology to allot a case to stage
IV.
Stage IVa Parenchymal liver metastases equals stage IVa.
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The Surgical procedure:
The goal of our surgical treatment is removal of the tumor as much as possible.(21,22)
Big supraumbilical vertical incision
- Peritoneal washing if no ascitis.
- Exploration of the whole abdominal cavity
- Biopsies were taken from :
- greater omentum
- Adhesion areas
- Pouch of Douglas
- Round ligaments
Surgical interventions, which consists of:
- Total abdominal hysterectomy and bilateral salpingoopherectomy.
- Debulking of all the tumor mass.
- Omentectomy and appendectomy.
- Multiple biopsies.
- Para aortic and iliac lymphadenectomy
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CONT..
Chemotherapy:
Combined chemotherapy protocol
consisting of Taxol and Carboplatin(27)
Second look laparatomy:
Laparotomy according to the technique of
Lippman (23)
- Peritoneal washing for cytology.
- Multiple biopsies were taken.
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Material & Methods
Our study involved a total number of 68 patients
diagnosed with stage III and IV ovarian cancer
(according to the FIGO classification) during the
time period between January 1990 and
December 1995 with a minimal follow up period
of 5 years.
The mean patients’ age was 56 years (range:34-
78 Years).
Parity: Nulliparous 24%, Multiparous 76%.
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Table 1:
Distribution according to Age, Parity and Abortion
STAGE III AND IV CA OVRAY DISTRIBUTION OF AGE AND PARITY
Max 75 Min 34 56 Years Age
0% 23% Nullipara Parity
0% 76% Multipara
0% 61% Nulligravida Abortion
0% 24% With abortion
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Table 2: Initial surgical treatment of ovarian cancer Stage III & IV.
STAGE III,IV CA OVARY INITIAL
SURGICAL TREATMENT
% N=68 Type of surgery
45.7% 31 Biopsy
17.6% 12 Cytoreductive
36.7% 25 Complete surgery
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Table 3:
Second look laparotomy among cancer group
STAGE III, IV CA OAVARY TREATED
WITH CHEMOTHERAPY
% N=68
26.47 18 Second-look
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Chemotherapy:
Five regimens were instituted in our patients:
Cisplatinum, Adriamycin, and Cyclophosfamide.
Intra-peritoneal cisplatinum.
Cisplatinum, Adriamycin, and clorambucil
Intraperitoneal Cisplatinum and bleomycin.
Cisplatinum, Adriamycin and Genoxal
Method of administration of intraperitoneal chemotherapy
2 L of normal saline was injected intraabdominal through a catheter followed by the administration of 200 mg/m2 of cisplatinum and sodium thiosulphate.
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R e s u l t:
DISTRIBUTION ACCORDING TO AGE
Age (years) N=68 %
31-40 3 4.410
41-50 12 17.65
51-60 30 44.12
61-70 17 25.00
71-80 6 8.820
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Table 6: Parity among the
malignant groups
Distribution according to parity in stage III and IV
ovarian cancer
Parity N=68 %
Nulliparous 16 23.53%
Primipara 4 5.88%
Multipara 41 60.30%
Unknown 7 10.29%
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Table 7:Distribution according to the presence
of ascitis in ovarian cancer stage III and IV
Ascitis N = 68 %
With 54 79.5
Without 14 20.5
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Table 8: Distribution according to the
peritoneal washing results in ovarian cancer
stage III and IV
Peritoneal wash Cases
Positive 4 cases
Negative 1 cases
Not done 9 cases
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Table 9: Distribution according to residual
tumor after salvage surgery among the cancer
groups
Residual mass Cases (n=22) %
No Residual
Tumor
7 cases 10%
Tumor < 2cm 5 cases 7%
Tumor > 2cm 10 cases 14.71%
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Table 10: Distribution of different stages of the
disease
Stage No. of patients %
Stage IIIa 4 5%
Stage IIIb 2 2%
Stage IIIc 32 47%
Stage IV 30 44%
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Table 11: Distribution according to the types in the
malignant groups
Histological type n=68 %
Serous
adenocarcinoma
40 58.80%
Muscinous
adenocarcinoma
5 7.35%
Endometroids 8 11.76%
Undifferentiated 7 10.00%
Mixed 3 4.41%
Clear cell carcinoma 5 7.35%
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Table 12: Distribution according to the
histological grades after treatment in Stage III,
IV ovarian cancer
Stage III, IV Ca ovary
Classification of histological grade
Histological
grade
N=68 %
GI highly date 12 17.60%
GII mild date 11 16.70%
GIII poorly 38 55.80%
Unknown 7 10.30%
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Table 13:Types of chemotherapy used among
the malignant groups
STAGE III, IV epithelial ovarian cancer adjuvant chemotherapy
Poly chemotherapy N=68 %
Cisplatinum, Adriamycin
and
cyclophosphamide
51 75.00%
Cisplatinum,Adriamycin
and Clorambucil
2 2.94%
Intraperitoneal,
Cisplatinum
14 20.59%
Cisplatinum +
Intraperitoneal
Bleomycin
1 1.47%
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Table 14: distribution according to number of
cycles patient tolerated among the malignant
groups
No. of cycles No. of patients %
Less than 5
cycles
17 25%
5 cycles 20 29.41%
More than 5
cycles
28 41.17%
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Table 15: Number of patients who had a
second-look laparotomy after chemotherapy
Second-look n=68 %
Done 18 26.47%
Not done 50 73.53%
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Table 17 :distribution according to the
evolution of the patient with advanced
epithelial ovarian cancer
Situation N=68 %
Persistent 32 47.06 %
Complete
response
13 19.12 %
Metastases 8 11.76%
Recurrence 12 17.64 %
Un known 3 4.42 %
Stage III and IV ovarian cancer
Evolution
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Stage III and IV ovarian cancer
Evolution
Situation n=68 %
Alive without
disease
13 19
Died due to tumor 51 75
Died due to another
cause
1 1.4
Don’t know 3 4.7
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Study of the survival rates among our patients
in stage III and IV epithelial ovarian cancer.
Figure 1: Survival rates for all groups of Patients
Global Survival rate
0
20
40
60
80
100
120
0 3 5 7 11 13 14 17 19 22 25 29 39 75
Months
Survival
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Figure 2: Distribution According to histological
types, Grades among the malignant groups
Survival according histological
type
0
20
40
60
80
100
120
0 3 6 9 10 12 15 18 19 24 28 39 75
Months
serous
mucinous
mixed
Undife.
Endometroide
Clear cell
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Figure 3: Survival rates according to the
histological grades among the malignant
groups
Survival rates according to histological grades
0
20
40
60
80
100
120
0 5 6 7 12 15 18 19 24 28 63 92
Months
Mildly
Poorly
highly
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Figure 4: Survival rates according to the stage
of the tumor.
Survival rates according to the stage
0
20
40
60
80
100
120
0 4 5 6 8 12 13 15 17 19 22 25 28 29 64 91
Months
Stage 3
Stage 4
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Figure 5: Actual calculation of survival rates
according to the route of administration of
chemotherapy.
0
20
40
60
80
100
120
0 4 5 7 8 11 13 15 17 18 24 27 29 39 75
Months
Intraperitoneal
Systemic
Survival rates according to the route of administration of chemotherapy
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Figure 6: Survival rates according to the
second - look laparotomy among the malignant
group.
0
0,2
0,4
0,6
0,8
1
1,2
SL neg.
SL post.
According to the second – look laparotomy
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Discussion
The 5-year survival rate for stage III ovarian carcinoma was found to
be 42.88 % and for stage IV it drops to 6 %.
Different authors report comparable percentage.
General Characteristics: -
1- Age:
The mean age of the patients was 56 years, 71 % of them were postmenopausal, which is approximately the same percentage reported internationally. Yancik, 1986(3)
2- Parity:
23 % nullipara.
76 % multipara, same result as Averette 1993(43) In contrary to most published articles, the incidence was found to be higher in nullipara.(5,6,9)
3- Presence of Ascites:
Absence of ascites was found to be a good prognostic factor
(P> 0.001). We are thinking as Dembo (33).
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Discussion
cont. 4- Residual tumor size:
Is an important prognostic factor, widely recognized by other researchers. If residual mass < 2 cm mortality rate increases and vice versa. (24,25,28,30,33,36,37,39,40,41,42,44,46)
5- Localization of the tumor:
In agreement with international sources, we found that survival rate is higher in patients with unilateral ovarian cancer.
6- FIGO staging:
The earlier the stage, the higher the survival rate coinciding with other studies.(31,32)
7- Histological type:
Survival rate in serous, mucinous and mixed tumors was found to be significantly higher than endometrioid and undifferentiated varieties.
8- Tumor grading: The more differentiated the tumor, the higher the survival rate
(P > 0.005).(28,31,35,45,48,49)
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Discussion
cont. 9- Primary debulking surgery:
Patients who underwent primary complete debulking surgery had better survival rates than those having incomplete surgery or biopsy alone.
10- 1st line chemotherapy:
When platinum was added to the chemotherapy regimen, survival rate was increased.(50,52)
Also intraperitoneal cisplatin was more efficient than systemic cisplatin.(26,51)
11-Number of cycles:
Increasing number of cycles increased the survival rate.
12- Second – look laparotomy:
In this study, a very important prognostic factor was the result of second-look laparotomy, patients with negative second look laparotomy had better survival rates. Frigerio(52)
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Conclusion:
1- The use of Systemic chemotherapy in patients with
minimal residual disease after a second look laparotomy proved to increase the survival rate.
2- The serous histological type has a better survival rate than other types.
3- Treatment at an early stage has a better survival rate than advanced stages.
4- The primary debulking surgery must be as complete as possible.
5- Residual mass less than 2 cm in size has a better survival rate.