Case Conference May 10th 2017

10-Mei-2017, Divisi Ginekologi Onkologi RSCM

CASE CONFERENCE

May 10^th, 2017

Mrs. X

Ovarian cancer stage IC3 (clear cell) postsurgical staging

 

Case Description:

Patient complained of abdominal mass and was underwent surgical staging at Royal Progress Hospital. The pathology result of the operation was ovarian adenocarcinoma, moderate differentiated grade II, chronic cervicitis, ovarian endometriosis cyst, omentum with inflammatory signs, chronic-nonspecific lymphadenitis (details were reviewed and attached below). The cytology result was adenocarcinoma. Patient was then referred to our hospital for further treatment.

 

Physical examination on March 10^th, 2017:

General status:

CM. BP: 120/70 mmHg, HR: 90 bpm, RR: 20x/m, T:36^oC, Height 158cms, Weight 66kgs

Head: Pale conjungtiva (+/+)

Neck: supraclavicula lymph nodes (-/-)

Axilla: lymph nodes (-/-)

Thorax: symmetry shape and movement of hemithorax

Cardia: no murmur, no gallop

Abd: linea mediana scar approx. 15 cm, no mass palpated.

Extremity: inguinal lymph nodes (-/-)

Gyn state: 

Inspection: normal external genitalia organ

Inspeculum: normal vagina, normal vaginal stump

RVT: normal vainal wall, normal vaginal stump, both parametriums within normal limit, TSA normal, rectal mass (-).

 

Ultrasound examination, April 10^th, 2017

Nonvisual uterus and both ovaries. Normal vaginal stump. No mass or active vascularization. No enlargement of lymph glands on bilateral parailiac and paraaorta region. No ascites. Liver and both kidneys normal.

Conclusion: ovarian cancer post total abdominal hysterectomy and bilateral salphingooovorectomies.

 

Review Patology Results, May 2^nd, 2017

Macroskopic:

11 pathology blocks PA no 1703043

Microskopic:

I.  Specimen after operation of HTSOB (tag “clinically ovarian cancer IC) consisted of uterus with tab IA-IC showed ectocervical part lined by squamous epithelial cells and endocervical part line by a layer of columnar epithelial cells. Endocervical glands were enlarged, cystic. Stroma cells were with limphocytes. Myometrium were within normal limit. Ovary specimen, tag ID, was with corpus albicans,. Cystic wall was seen with a layer of cuboid cells with some of hemosderofag and lymphocyte cells. Specimen with tag IE and IF showed malignant epithelial tumor mass formed glandular structure, papiler until solid structure, with necrotic area. Hyalinated stroma. Tumor cells were polygonal, nucleus polymorphic, vesicular, hyperchromatic, rough chromatin, partially with nucleoli. Cytoplasm was eosinophilic or clear. There was mitosis. Specimen of omentum (tag II) consisted of mature fat tissue and connective tissue with inflammatory cells acute and chronic and hemosiderophag. No tumor mass on omentum. Specimen of appendix (tag III) showed appendix tissue lined by columnar epithelial cells with goblet. Some limfoid follicles were shown with neutrophils, plasmic cells, limphocytes on lamina propria. Specimen of paraaorta lymph glands (tag IV) consisted of 3 lymph glands with no tumor, and specimen of left lymph glands (tag VI) consisted of 3 lymph glands with no tumor.

Conclusion: histology of clear cell ovarian carcinoma, moderate differentiated. There was ovarian endometriosis. No tumor mass on omentum, paraaortal lymph glands, right and left iliac pelvic glands. No tumor mass on uterine wall.

 

Cytology of peritoneal washing results, March 26^th, 2017

Contained of malignant cells, pleomorphic, hyperchromatic, vesicular, nucleoli with basophilic/clear cytoplasm.

Conclusion: adenocarcinoma

 

 Selection

From the articles, limitation was given for clinical trial, no abstract, not available in full text, not written in English, or articles which had no related titles. After the process, there were 2 articles appropriate for discussion.

 

Critical Appraisal

Article 1. International Collaborative Ovarian Neoplasm Trial 1: a randomized trial of adjuvant chemotherapy in women with early-stage ovarian cancer. J Natl Cancer Inst 2003;95:125–32.

Article 2. Randomized Phase III Trial or Irinotecan Plus Cisplatin Compared with Paclitaxel Plus Carboplatin as First Line Chemotherapy for Ovarian Clear Cell Carcinoma. J Clin Oncol. 2016 Aug 20;34(24):2881-7.

Discussion

Study of ICON-1 revealed that platinum-based adjuvant chemotherapy improved survival and delayed recurrences in patients with early stage ovarian cancer after surgery. This was regardless of any types of histology. The study’s characteristics showed patients included in the study were 144 patients of serous type, 103 of mucinous type, 103 of endometrioid type, and clear cell type was 67 patients. Women who received adjuvant chemotherapy had better overall survival than women who did not (hazard ratio [HR] of 0.66, 95% confidence interval [CI] = 0.45 to0.97; P = 0.03). A parallel trial conducted by EORTC (ACTION trial) included 488 early ovarian cancer patients after complete or incomplete surgical surgery from 40 centers for randomization for chemotherapy or observation. The result showed that regardless any histopathology types, adjuvant chemotherapy of platinum based showed adjuvant chemotherapy was associated with statistically significantly improved recurrence-free survival in patients with early-stage ovarian cancer. The benefit of adjuvant chemotherapy appeared to be limited to patients with non-optimal staging, i.e., patients with more risk of unappreciated residual disease. The ACTION trial mature data was published 10 years later and it supported for most of the main conclusions of the original analysis, except that overall survival after optimal surgical staging was improved, even among patients who received adjuvant chemotherapy (hazard ratio of death = 1.89, 95% confidence interval = 0.99 to 3.60; overall two-sided log-rank test P = .05).

Due to different characteristics of clear cell which mostly were associated with poor response to platinum based chemotherapy, a novel treatment was still in search to find a better approach. Although, Timmers PJ et. al. showed that no worse prognosis in patients with CCC as compared with patients with serous carcinoma in early ovarian cancer in a large randomized trial.

Another phase III RCT has been performed to replace the role of platinum based chemotherapy for clear cell ovarian cancer. Sugiyama et. al. involved 667 patients with stage I to IV clear cell carcinoma of the ovary were randomly assigned to receive irinotecan 60 mg/m2 on days 1, 8, and 15 plus cisplatin 60 mg/m2 on day 1 (CPT-P group) every 4 weeks for six cycles or paclitaxel 175 mg/m2 plus carboplatin area under the curve 6.0mg/mL/min on day 1 every 3 weeks for six cycles (TC group). The primary end point was progression free survival. Secondary end points were overall survival, overall response rate, and adverse events. Six hundred nineteen patients were clinically and pathologically eligible for evaluation. With a median follow-up of 44.3 months, 2-year progression-free survival rates were 73.0% in the CPT-P group and 77.6% in TC group (hazard ratio, 1.17; 95% CI, 0.87 to 1.58; P = .85). Two-year overall survival rates were 85.5% with CPT-P and 87.4% with TC (hazard ratio, 1.13; 95% CI, 0.80 to 1.61; one-sided P = .76). Grade 3/4 anorexia, diarrhea, nausea, vomiting, and febrile neutropenia occurred more frequently with CPT-P, whereas grade 3/4 leukopenia, neutropenia, thrombocytopenia, peripheral sensory neuropathy, and joint pain occurred more frequently with TC. No significant survival benefit was found for CPT-P. Both regimens were well tolerated, but the toxicity profiles differed significantly. Treatment with existing anticancer agents has limitations to improving the prognosis of CCC.

 

Conclusion

 

According to the efficacy and feasibility of ovarian cancer treatment in our country, platinum based chemotherapy is still the choice for clear cell ovarian cancer. 

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