PATIENTS AND METHODS
Eligibility Criteria & Pre-treatment evaluation
We analysed hospital records of all children less than 18 years with a histopathologically confirmed diagnosis of extracranial GCT over a period of 10 years (January 2009 to December 2018), who were treated on a uniform institution-based protocol at the Tata Memorial Hospital, Mumbai, India. Children who received prior chemotherapy or radiotherapy were excluded. However, children who were operated outside and received adjuvant therapy at our centre were included in the analysis (Figure 1).
Pre-treatment evaluation of all children included complete clinical examination with complete blood count, serum electrolytes, renal and liver function tests, lactate dehydrogenase and tumor markers including serum AFP and beta-HCG. While the cut-off for beta-HCG elevation was taken as 5mIU/L, AFP was deemed elevated if it was more than 5 times the mean level for that age9. Staging imaging consisted of Magnetic Resonance Imaging (MRI)/Computed tomography (CT) of the local site and contrast CT scan of the chest and liver.
Surgical resection was attempted upfront if feasible. In the event of significant surgical morbidity or tumors deemed unresectable, children underwent delayed surgery after 2-4 cycles of neo-adjuvant chemotherapy. Tissue diagnosis at baseline was obtained in children who underwent either a primary surgical resection or a diagnostic biopsy (especially in non-secretory GCTs). Patients who presented with elevated tumor markers with suggestive imaging findings did not undergo an upfront biopsy, and diagnosis in this subset was established post-surgery. Staging of the tumors according to the primary anatomical site was done prior to starting treatment as per COG Staging10.
All testicular tumors underwent resection by way of high inguinal orchiectomy. A trans-scrotal biopsy however warranted a completion orchiectomy following upstaging to Stage II. Children with RPLN (retroperitoneal lymph node) of size > 1cm on baseline imaging and RPLN<1cm coupled with persistence of elevated AFP (post orchiectomy) were stratified as Stage III. The decision of RPLN dissection was taken on a case-to-case basis and not routine. Ovarian tumors were operated and staged as per COG guidelines11. Ascitic fluid was collected for cytological examination and in the absence of the former, intraoperative peritoneal washings were sent. While the decision of primary surgical resection in extragonadal tumors depended on the site and discretion of the treating surgeon, the usual practice was to perform a delayed resection after 2-4 cycles of neo-adjuvant chemotherapy unless it was radiologically consistent with teratoma. In sacrococcygeal tumors, resection of the tumor with coccygectomy was the procedure of choice. In large intrapelvic tumors/retroperitoneal tumors sometimes presenting with obstructive uropathy, neoadjuvant chemotherapy followed by definitive resection until after four chemotherapy cycles, was the preferred plan. A similar approach was followed for mediastinal tumors too, via a median sternotomy or lateral thoracotomy.
The following pre-specified variables were collected from the cohort: demographic data, radiological and biochemical parameters for diagnosis including tumor markers, stage and risk of the disease, primary and adjuvant therapies, chemotherapy regimen and complications during treatment and outcome.