Ovary Flashcards
Do you perform upfront lymphadenectomy in patients during surgical debulking?
No.
This is based on the LION trial (Lymphadenectomy in Ovarian Neoplasm).
A prospective, randomized study which showed no difference in PFS or OS with systematic LND in stage II-IV patients undergoing debulking.
LND did have higher EBL, longer OR time, longer re-admission rates.
PFS was 25mo, OS was 65 and 69mo.
Do you give chemotherapy to Stage I epithelial ovarian cancers?
Yes.
There have been two prospective, randomized trials (ICON1 and ACTION) which demonstrated that adjuvant chemotherapy resulted in improved outcomes in early-stage ovarian cancers.
The two trials were merged, showing a RFS 76 vs 65%, and OS 82 vs 74% with chemotherapy.
What are the criticisms of ICON1?
In ICON1, patients did not have to be fully surgically staged. Therefore, the trial likely included occult Stage III patients.
ACTION details.
How did ACTION differ from ICON1?
ACTION evaluated the extent of staging that was done and evaluated the role of adjuvant treatment in patients based on whether or not they were fully staged.
Adjuvant chemotherapy was associated with an improved RFS in early stage patients, but this benefit seemed to be limited to patients who did not have optimal staging. In other words, in patients who may have had occult higher stage disease.
Optimally staged patients had improved RFS and OS in the observation group, but not in the chemotherapy group.
1) How much chemotherapy do you give early stage ovarian cancer patients?
2) What is this based on?
1) Grade 1, Stage IA or IB: observation
Serous, or Stage II: C/T x 6
All others: I recommend at least 3 cycles and then assess the patient for tolerance to treatment, with subsequent cycles given unto 6 total if there is minimal toxicity.
2) GOG 157 was a prospective, randomized trial looking at 3 vs 6 cycle of chemotherapy, and found no difference in RFS or OS, however higher toxicity with 6 cycles.
- An ad hoc analysis of this study showed that it may be limited to serous tumors.
What is the difference between 24hr and 3hr taxol when used with cisplatinum?
There is more neurotoxicity with the 3hr dose.
This was demonstrated in GOG 111 and OV-1, in which the rates of neurotoxicity were 4 and 14%, respectively.
*This is why Iowa uses 24hour taxol with cis.
What is the 5 year survival for ovarian cancer patients by stage?
Stage I - 80%
Stage II - 60%
Stage III - 40%
Stage IV - 30%
How do you treat Stage IV patients?
I evaluate Stage IV patients with criteria similar to Stage III patients, assessing them for medical fitness to undergo surgery, and assessing their disease burden on imaging for degree of resectability.
There is limited data on Stage IV patients. At least four retrospective studies have shown improved outcomes in Stage IV patients who achieved optimal vs suboptimal cytoreduction.
What are the theoretical ways in which tumor debulking improves patient outcomes?
- Decreased patient discomfort
- Reduces metabolic consequences of the tumor
- Enhances patient’s ability to maintain nutrition
- Improves response to chemotherapy: large tumor volumes have poor blood supply, and therefore may be a sanctuary for tumor cells to escape chemotherapy. In addition, poorly vascularized masses may have lower growth fraction.
What data are there to support debulking in advanced stage patients?
- Hoskins 1994: tumor diameter. This study looked at suboptimally debulking patients and demonstrated that there was a survival advantage in patients who had 1-2cm residual disease compared to patients who had >2cm disease.
- Bristow published a meta-analysis in 2002 that for every 10% increase in cytoreduction, there is a 5% increase in median survival.
- du Bois in 2009: R0 disease. This analysis combined 3 AGO-OVAR studies, and concluded that patients who were completely cytoreduced had improved outcomes over those with 1cm and >2cm residual disease.
How do you assess the degree of resectability in advanced stage ovarian cancer patients?
This is based on a combination of physical exam, and the patient’s imaging. I assess the patient with a complete physical exam, and a CT. On CT, findings that would suggest unresectable disease include involvement of the bowel mesentery, the lesser sac or its structures, deep parenchymal liver mets, or involvement of the port hepatis.
Do you use laparoscopy to evaluate resectability of advanced ovarian cancer?
I do not. However, such an approach is used by other members of our field. Specifically, laparoscopy can be used to survey the abdomen and pelvis, with attention paid to the presence or absence of an omental cake, peritoneal carcinomatosis, diaphragmatic carcinomatosis, mesenteric retraction, stomach infiltration, and liver metastases. The Fagotti laparoscopic score then gave 0-2 for each of these parameters, and cytoreduction was suboptimal in all patients who had a score >= 8
How did we arrive with carbo/tax as the standard of care?
- Omura 1986: CA vs CAP. The addition of cisplatin improved OS.
- Further studies confirmed the utility of platinum-based regimens
- - ICON2: carbo = CAP, but with fewer SE
- - GOG 132: cis vs taxol vs cis/taxol; both platinum groups were better than the taxol-alone group. - (1996) GOG 111: cis/taxol had improved outcomes over cis/cyclophosphamide.
- - (2000) Piccart: This was confirmed by an international trial. - (2003) GOG 158: NON-INFERIORITY TRIAL that showed carbo/taxol was non-inferior to cis/taxol, and that carbo/taxol had less toxicity.
- (2003) du Bois: confirmed by AGO-OVAR3
Thus, carbo/taxol became the standard of care.
How do the toxicities of cisplatin and carboplatin compare?
All platinums have nausea, emesis, neurotoxicity, and nephrotoxicity. Carboplatin is more myelosuppesive, but otherwise better tolerated when compared to cisplatin.
How do GOG 111 and the confirmatory Intergroup study differ?
Both studies looked at cis/taxol vs cis/ccp.
GOG 111: 24 hours taxol.
Intergroup study: 3 hour taxol
