Dr Jane Skeen- for the NZ NCCN Pacific working group Germ cell Tumours Fiji 1 December 2016 Dr Jane Skeen- for the NZ NCCN Pacific working group

Germ cell tumours Rare and highly varied group of tumours Occurs at several anatomical sites Histological spectrum from mature to immature teratoma to 4 different malignant subtypes Prior to platinum based chemotherapy -survival poor BEP :bleomycin etoposide and cisplatin – nephro and ototoxic JEB : bleomycin etoposide and carboplatin

Risk groups LOW INTERMEDIATE HIGH Gonadal Stage 1 (regardless of AFP) Testis <5yrs, any AFP, Stages 2-4 All Stage 4 tumours except testis <5yrs and germinoma and seminoma Testis ≥5yrs, AFP <10000, Stage 2+3 AFP ≥10000 except all Stage 1 tumours and testis <5yrs Stages 2-4 All other sites AFP <10000, Stage 2+3, except thoracic tumours All thoracic tumours Stages 2-4 Pure germinoma, seminoma, any site, Stages 2-4 Pure HCG secreting tumours, any HCG, Stage 2+3

Histological classification Germ cell tumours Germinoma Teratoma -Mature -Immature -Malignant teratoma Embryonal carcinoma Yolk sac tumour Choriocarcinoma Gonadoblastoma Mixed malignant germ cell tumour

PI GC 1 Protocol 6* cycles of identical treatment for all stages and histologies Carboplatin (JM8), Etoposide, Bleomycin (JEB) Each cycle 21 days (* Number of cycles (x+2) where x is the number required to achieve CR) CR assessment will be assisted by ability to measure and follow appropriate tumour markers  Total therapy duration usually no more than 6 months

Initial Evaluation Complete history including family history. Complete physical examination Chest X-ray and abdominal ultrasound. CT scan of affected area plus chest and abdomen . Full blood and platelet count. Urea, creatinine, electrolytes, calcium, liver function tests Tumour Markers- alpha fetoprotein / βHCG / Ca 125

Eligibility/Treatment All patients with biopsy proven Germ cell Tumours (with the exception of Stage 1 Testicular tumours) Stage 1 testicular tumours that post-orchidectomy show decreasing AFP at expected rate, will receive no further treatment unless there is arise in the AFP or clinical recurrence. The initial cycle of therapy should be given as soon as practically possible after appropriate supportive care has been given. This will include correction of anaemia (if applicable), treatment of infection and any co-morbidities.

Treatment The half-life of alpha fetoprotein is 4-7 days AFP levels should reduce by at least 50% each week. If AFP fails to normalise or having fallen starts to rise again, reimaging indicated, with a view to second look surgery.

9 yr old - female January 2007 presented with a painful distended abdomen History of becoming unwell whilst on extended holiday Transferred to Starship Imaging : an extensive non-calcified abdomino-pelvic mass, ascites, peritoneal and subdiaphragmatic deposits AFP (alpha-fetoprotein) > 60,000 units Presumptive diagnosis : Germ cell tumour

12.1.07 Laparotomy and biopsy of mass large intra-operative bleed tumour appeared necrotic omentum was studded with nodules presumed prior tumour rupture urinary output compromised due to the raised intra- abdominal pressure related to the ascites

Chemotherapy commenced carboplatin/etoposide (JE) Evening of 18.1.07 collapsed Resuscitated then admitted to PICU for ventilation Abdomen decompressed after insertion of pigtail catheter under ultrasound guidance 3 litres of ascitic fluid was drained and the catheter remained in situ

Histology : tumour was haemorrhagic and necrotic with a typical endodermal sinus pattern Features of yolk sac tumour with positive markers for alpha-fetoprotein, other tumour markers negative No ovarian tissue seen in the biopsies Presumed extra gonadal advanced stage III yolk sac tumour Presumed that tumour ruptured pre-biopsy with subsequent peritoneal seeding (family later stated abdominal massage) With chemotherapy- good chance of cure

α-FP decline

Received 6 cycles chemotherapy ( JE/JEB x5) (carboplatin/Etoposide/bleomycin) Post cycle 6 : AFP 46.4 (N< 10) Second look surgery 21 May: right ovary normal left in situ- some residual tissue resected 28 May AFP 11.4 Histology- no viable tumour 5 June AFP normal 4 Remains well AFP normal Last reviewed September 2016 Wants to join the Navy