Case Conference June 21th 2017

21-Jun-2017, Divisi Ginekologi Onkologi RSCM

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21  June, 2017

MissY

 

Case Description:

Patient had post-operation  with digestive-surger and the result was dysgerminoma in Mei 2016.

Patient already given BEP three times (the last in 13rd April 2017). Patient referred from Wahidin hospital. Patient had an ovaries operation history in Papua 2013. Last MRI result Solid mass conglomerated in paraaorta ,which start from proximal , bifurcation until right-left parailiaca, covered all vascular lumen

 

Physical examination on May 12th, 2017:

General status:

CM. BP: 103/63 mHg, HR: 65 x/min, T: 36C, RR: 20 x/min,

Head: Pale conjungtiva (-/-)

Neck: supraclavicula lymph nodes (-/-)

Axilla: lymph nodes (-/-)

Thorax: mammae lump (-/-) mass (-/-),  symmetry shape and movement of hemithorax

Lung: vesicular breath sound on both lungs, no wheezing or rhales

Cardia: no murmur, no gallop

Abd: flat, no palpable mass

Extremity: inguinal lymph nodes (-/-)

 

Gyn state:  

Inspection: external  genitalia was normal

Rectovaginal: vulva urethra wasnormal, vaginal wall smooth, mass sized 6x5 cm, both of parametrium was normal, TSA was normal, mass in rektum (-).

 

Pathology Anatomy Result from Wahidin Sudirohusodo Hospital, May 18th, 2016

Macroscopic:

One tissue sized 10x8x3 cm, colour: brownish white, elastic, 2 cassettes.

Microscopic:

All tissue fulfilled with tumor mass, including cell nest with round nuclei monoton relatively, at cental, nucleoli prominent, lot of sitoplasm, clear, divided by terdiri dari sarang-sarang sel dengan inti bulat relative monoton, ditengah, nucleoli prominen, sitoplasma banyak, clear, divided by a few of fibrous connective tissue septa. 

Summary:

The above description appropriate to describe a dysgerminoma

 

USG result, June 12th, 2017

Description: Uterus RF, shaped and sized normal. Myometrium homogen. Endometrium thin. Stratum basalis regular. Cavum utery empty. Portio and endoserviks normal. Right ovary no visual (suitable as post SOD). Left ovary in behind corpus uteri. Vascular widening in left adnexa. Hepar and both renal normal. No ascites. Echogenic mass in anterior aorta sized 41x83x24 mm , which origined from the malignancy (teratoma?)

Summary: Right ovary non visual. Anterior aorta mass susp malignancy (teratoma?)

 

MRI Lower Abdomen /Pelvis result, May 03rd, 2017

Fluid accumulation in di paravesica and paracolica bilateral.

multiple lymph gland in inguinal bilateral with the biggest diameter +/- 1,1 cm in left inguinal. Intestines structures not showed thickening of intestines wall, dilatation or mass. Vesica Urinary have distended and normal with not thickening wall.

Utery: shaped and sized normal. There is no signal intensity and pathology stinging . Left Adnexa : there is cystic lession with the biggest size is  +/- 0,7 cm. Shaped and articulation of caput femoris and acetabulum aare normal, bone marrow normal.

Summary: Left cyst adnexa amount and size decreased. Ascites

 

Chest X-ray May 31st, 2017

Summary: There is no radiologic abnormality in cor and pulmo

 

MRI Upper Abdomen result, May 03rd, 2017  

Solid mass conglomerated in paraaorta ,which start from proximal , bifurcation until right-left parailiaca, covered all vascular lumen with sized +/- 2,2x6,8x13,2 cm (before: +/- 8x15,1x19,3 cm). There is no hepar nor pancreas crowding. Fluid accumulation in paravesica and  paracolica bilateral.

Right renal: size and position normal. Renal Parenkim showed normal internal structure. Pelvis renis and calises normal. There is widening of pelviokalises.

Left renal: size and position normal. Renal Parenkim showed normal internal structure. Pelvis renis and calises normal. There is no widening of pelvicocalices nor ureter. Gall bladder not in the field of view.

Lien: shape, size and smooth border ,and signal intensity homogeny.

Caput signal, corpus and cauda pancreas homogeny. There is no pathologic signal intensity. Duktus pankreatikus not widened or narroed. Intestines structure not showed intestine wall thickening, dilatation or mass. 

Summary: Conglomerated mass in paraaorta proxsimal, bifurcation until right-leftparailiaka, sized not significant. Right Hidronefrosis. Ascites. 

 

Chemotherapy Response

Pre chemotherapy:

Solid mass conglomerated in paraaorta start fromproksimal, bifurcation until right-left parailiaka, covered all lumen vascular with sized +/- 8x15,1x19,3 cm

LDH 2125

AFP 2,7

Post chemotherapy:

There is still visible a  solid mass conglomerated in paraaorta start from proksimal, bifurcation until right-left  parailiaca, covered all vascular lumen with sized +/- 2,2x6,8x13,2 cm 

LDH 418

AFP 3,8

 

Introduction

Dysgerminomas are relatively uncommon among all ovarian neoplasms (accounting for only about 2 percent), they account for 32.8 percent of malignant ovarian germ cell tumors (OGCTs). The majority of cases (75 percent) arise in adolescents and young adults, in whom they account for about one-third of all ovarian malignant neoplasms. Because of their predilection for young women, they are one of the more common ovarian malignant neoplasms detected during pregnancy. Nevertheless, dysgerminoma can occur at any age; case reports have described patients with dysgerminoma between 7 months and 70 years of age.

A clinical management dilemma facing gynecology oncologists when a young patient with apparent stage IA pure ovarian dysgerminoma (POD) who has not undergone comprehensive surgical staging is referred to a secondary center is whether to recommend adjuvant chemotherapy, surveillance or surgical restaging.

 

CLINICAL QUESTION

Is laparotomy debulking better than chemotherapy in this patient (Patient with recurrent dysgerminoma post Inadequate surgical staging post chemotherapy)? 

 

What question did the study ask? PICO Analysis

Patient Recurrent dysgerminoma

Intervention Surgical 

Comparison Chemotherapy

Outcome Progression free survival

 

METHODS

Search strategy

The search was conducted on Pubmed, Science Direct, and Up Todate  on June 19th 2017, using the search tool containing the keyword “Recurrent dysgerminoma, surgical staging, Chemotherapy, Progression free survival ” (Table 1). 

Search results were filtered by the engine according to the following criteria : articles published in the past 10 year, human species, and English language. Search strategy, result, and the inclusion and exclusion criteria are shown in the flowchart (Figure 1). 

Table 1. Search strategy used in Pubmed, Science Direct and  Uptodate, conducted on June 19th, 2017

Engine Search Terms Results

Pubmed

Recurrent dysgerminoma, surgical staging, Chemotherapy, Progression free survival70

 

 

               Figure 1. Flowchart of search strategy

     

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Selection

The titles of the filtered results from Pubmed were screened using the inclusion criteria. A second screening was conducted by reading the abstract, and finally 5 articles were found. 

Critical Appraisal

Two article Jeong-Yeol Park, et al. Outcomes of Surgery Alone and Surveillance Strategy in Young Women With Stage I Malignant Ovarian Germ Cell Tumors. Int J Gynecol Cancer 2016 and Mangili G. et al, Outcome and Risk Factors for Recurrence in Malignant Ovarian Germ Cell Tumors, A MITO-9 Retrospective Study

Table 2. Critical appraisal 

 

St

 

Study

          Criteria Jeong-Yeol Park, et al. Outcomes of Surgery Alone and Surveillance Strategy in Young Women With Stage I Malignant Ovarian Germ Cell Tumors. Int J Gynecol Cancer 2016 Mangili G. et al, Outcome and Risk Factors for Recurrence in Malignant Ovarian Germ Cell Tumors, A MITO-9 Retrospective Study

 

DOES THIS REVIEW ADDRESS A CLEAR QUESTION?

Is there a clearly focused question? Yes Yes

Was the cohort recruited in an acceptable way? Yes Yes

ARE THE RESULTS OF THIS REVIEW VALID?

Were there clearly defined groups of patients, similar in all important ways other than exposure to the treatment or other causes? Yes Yes

Were treatments/exposures and clinical outcomes measured in the same way for both groups? Yes Yes

Was the assessment of outcomes either objective or blinded to exposure? No No

Was the follow-up of study patients sufficiently long for the outcome to occur? Yes Yes

Do the results of the harm study fulfill some of the diagnostic tests for causation? Yes Yes

ARE THE RESULTS IMPORTANT?

How strong is the association between exposure and outcome, i.e. the estimate of risk? NA NA

How precise is the estimate of risk? NA NA

ARE THE RESULTS IMPORTANT FOR MY PATIENT?

Is my patient so different from those included in the study that its results don’t apply? Yes Yes

What is my patient’s risk of the adverse event/potential benefit from therapy? Yes Yes

What are my patient’s preferences, concerns and expectations from this treatment? Yes Yes

What alternative treatments are available? Yes Yes

 

Discussion

Dysgerminoma is the second most common ovarian germ cell tumor, but accounts for less than 2% of all ovarian malignancies; it is commonly diagnosed in the 2nd or 3rd decade of life. Dysgerminoma usually presents as an abdominal mass associated with pain, the onset of which may be acute in case of rupture, hemorrhage, or torsion of the mass. Approximately 5% of dysgerminomas are discovered in phenotypic females with abnormal gonads. Dissemination is more often lymphatic than intraperitoneal. Pure dysgerminomas do not secrete hormones but have been associated with increased human chorionic gonadotropin (HCG), CA-125, and LDH levels. About 70% of dysgerminomas are stage I and approximately 85–90% are confined to one ovary. Fertility-sparing surgery with peritoneal and lymph nodal staging is the standard treatment for patients with stage IA disease, while platinum-based chemotherapy or radiotherapy is reserved to relapse. 

A clinical management dilemma facing gynecology oncologists when a young patient with apparent stage IA pure ovarian dysgerminoma (POD) who has not undergone comprehensive surgical staging is referred to a secondary center is whether to recommend adjuvant chemotherapy, surveillance or surgical restaging. 

Complete surgical staging is generally required to enter a close surveillance program. Comprehensive surgical staging allows to identify patients with a more advanced stage disease that should receive adjuvant chemotherapy. As dysgerminoma spread principally follows the lymphatic way, lymph node dissection seems particularly important for a correct assessment of the amount of disease. Kumar et al. reported a prevalence of lymph node metastasis of 28% in patients affected by dysgerminoma, and the presence of lymph node involvement was an independent predictor of poor survival. 

It is estimated that about 15% of completely resected POD will recur and will be potentially cured at relapse. Vicus reported 4 cases of relapsed patients with unstaged IA POD which were all cured at relapse thus questioning the need of complete surgical staging in patients who can be cured at relapse. On the contrary Kasenda reported 2 cases of patients with apparent IA, surgically unstaged ovarian dysgerminoma, who received extensive surgery and multiagent chemotherapy at recurrence, causing renal insufficiency due to ureteral obstruction in one of them. The authors concluded that comprehensive initial surgical staging, including systematic para-aortic lymphadenectomy and man- agement of the patient in a tertiary referral center, is mandatory to minimize treatment burden. 

Dysgerminoma recurrences are reported to occur mainly within 12 months after initial treatment. In this dataset two patients relapsed within 24 months, and a patient recurred after 11 years. Including our patient, only 14 late recurrences are reported in literature. In our series an apparent ovarian recurrence at ultrasound evaluation revealed to be a benign teratoma at histological exam after cystectomy: previous studies reported that benign cystic teratoma is found in 5–10% of patients with malignant ovarian germ cell, highlighting the fact that bilateral ovarian involvement does not automatically herald a malignant process. 

Fertility-sparing surgery and complete surgical staging should be the treatment of choice of stage IA POD. In our dataset, 9 patients underwent radical surgery: three patients were in peri-menopausal age, 5 had gonadal dysgenesis and one patient's reasons are unknown. The presence of XY dysgenetic gonads precludes fertility-sparing surgery: patients should undergo bilateral gonadectomy because of the increased risk of contralateral malignant germ cell ovarian tumors; uterus may be left in situ for possible future embryo transfer. In literature less than 12 successful pregnancies following ovum donation and in vitro fertilization have been reported. In our study we report 2 cases of successful pregnancies after conservative bilateral gonadectomy without adjuvant chemotherapy in 2 46 XY gonadal dysgenetic women with gonadoblastoma and dysgerminoma. 

This goes with the international guide- lines e.g. ESMO and NCCN that advocate that stage IA pure dysgerminoma can be treated with surgery only. Recurrence rate in this group of patients is relatively low (15–25%) and they can be successfully treated at the time of relapse with a high likelihood of cure. Some published data indicate that all grades of immature teratoma can be managed with close surveillance after fertility-sparing surgery, reserving chemo- therapy for those cases in which post-surgery recurrence is documented. Only one of the 6 followed-up cases relapsed after 17 months and achieved CR after receiving BEP for 4 cycles. 

In the current study, no cases received radiotherapy despite the high radio-sensitivity of dysgerminomas. Historically, radiotherapy was used in many stage I dysgerminomas and in all patients having higher stage tumors with the field and dose determined by the stage. However, this approach has many reported long-term toxicities. In the current routine practice, radiotherapy is rarely performed since che- motherapy is equally or more effective, less toxic and less likely to compromise gonadal function. 

Whenever indicated, platinum-based combination chemo- therapy is the norm both in the early as well as in the advanced stages of ovarian GCTs with BEP ranking the first regimen. Data from the current study fit within these norms. Che- motherapy was administered in 63% of cases; 6 had teratoma and 6 had dysgerminoma {6 cases had stage I, 2 cases had stage II, and 4 cases had stage III}. BEP was the commonest regimen used (91.7%). In the current study, two teratoma patients received second-line chemotherapy either ifosfamide/epi- rubicin or paclitaxel carboplatin with poor response. This reflects the poor management of women who have persistent/ resistant disease after first-line chemotherapy or who progress within 4–8 weeks of completing adjuvant treatment. Results with salvage regimens and high-dose chemotherapy are poor in the setting of platinum-refractory disease. 

Relapses were documented in two patients reflecting the good prognosis of this disease. One had stage III teratoma and received paclitaxel/carboplatin as first-line and relapsed 17 months after end of therapy. The other patient had stage IA dysgerminoma under active surveillance and relapsed 12 months after surgery. Both received BEP. Relapse site was para aortic LN’s and pelvis and this is different from the usual presentation as 75% of GCT recurrences occur with in the first year after initial treatment and the most common site is the peritoneal cavity, more rarely retroperitoneal lymph nodes. 

Patients with completely surgically staged IA dysgerminoma should undergo surveillance. Management options of patients with apparent stage IA POD are either laparoscopic restaging or surveillance. Further studies are required to establish whether restaging or surveillance is the best approach. If the salvage rate of 100% at relapse will be confirmed, restaging would subject too many patients to unnecessary major procedures. BEP chemotherapy should be reserved for treatment of relapse with a high cure rate. 

In conclusion, our data suggest that surgery followed by chemotherapy was the best approach for this patient. Given the type of germ cell tumor was dysgerminoma complete resection of recurrent mass will be expected to give a good result.

 

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