Table 1 summarises the patient demographic and clinical characteristics
of patients with malignant GCTs (n-254). Gonadal GCTs were more common
than extragonadal tumors with ovary being the primary site in 128
children (43%) and testis in 52 children (17.5%). While testicular and
extragonadal tumors were more common in children<3 years
(82.6% and 77.7% respectively), ovarian tumors were seen in a higher
proportion in children>11 years (61%). Metastatic disease
was noted in 75 patients (25.3%) with lungs being the commonest site
(Isolated-41; in combination-10). Non-pulmonary visceral metastases
(NPVM) were seen in the remaining patients, of which liver was the most
common site (Isolated-14; in combination-12). Pre-chemotherapy
histopathological subtype was available in 253 (85%) cases, of which
yolk sac tumor was the commonest (109/253; 43%). In the remaining
patients, the tumor was presumptively treated as germ cell tumor based
on imaging and elevated TM, and histology was established
post-chemotherapy as residual teratomas. Amongst all yolk sac tumors
(n-151), AFP was uniformly elevated with a median value of 16839 IU/mL
(99-856496 IU/mL). AFP upwards of 1000 IU/mL was seen in 129 patients
(85%).
On univariate analysis, gonadal sites, low risk tumors and
non-metastatic tumors were associated with better EFS and OS, which was
statistically significant (p<0.05). Amongst the malignant GCTs
(n-254), low risk and standard risk 2 groups had a better OS compared to
other groups. In addition, the type of chemotherapy regimen (PEb or JEb)
did not have any impact on EFS or OS. However, a small proportion of
patients who received the hybrid regimen had unfavourable outcome. Table
2 shows the survival outcomes against the known prognostic variables.
On multivariate analysis, Stage IV GCT had an inferior EFS (RR: 2.96;
95% CI: 1.24 - 7.08; p=0.015) and OS (RR: 19.93; 95% CI: 2.46 -
161.25; p=0.005). Additionally, extragonadal GCTs had a poor EFS (RR:
1.98; 95% CI: 1.20 - 3.29; p=0.007) and OS (RR: 3.09; 85% CI: 1.65 -
5.79; p<0.001). The aforementioned prognostic variables failed
to retain their prognostic significance when computed for, in the subset
of malignant GCT. Children who received hybrid regimen had an inferior
OS (RR: 2.86; 95% CI: 1.30 - 6.29; p=0.009). Age, gender and baseline
AFP did not have any bearing on EFS or OS in either subsets. The
demographic and survival correlates of individual group of malignant
GCTs is described below:3a. Ovarian GCTs: One hundred and fourteen patients were
eligible, of which 55 (48.2%) underwent surgery prior to presentation.
Lack of thorough surgical steps, including failure to collect peritoneal
washings/ascitic fluid for cytology led to upstaging in 41 patients
(75%) in this subset. Twelve patients relapsed. At a median follow-up
of 54 ± 38.27 months, the 5 year EFS and OS at a median follow up of
52.5 ± 32.1 months was found to be 85.9% and 90.3% respectively.3b. Testicular GCTs:Forty-eight patients were eligible for
analysis. Thirty-five (73%) patients underwent surgery outside, of
which 23 (47.9%) underwent high inguinal orchiectomy. Adjuvant
chemotherapy was needed in 30 patients. Seven patients relapsed (2 in
Stage I; 1 each in Stage II & III; 3 in Stage IV). At a median
follow-up of 52.82 ± 39.3 months, the 5-year EFS/OS was 82.3%/91.7%.
Patients who underwent surgery/biopsy prior to presentation had an
inferior EFS, but this association was not statistically significant
(79.5% v/s 90.9%; p=0.388).3c. Extragonadal GCTs:Amongst the extragonadal GCTs
(n-92), sacrococcygeal tumors were the commonest (41; 44.6%) followed
by retroperitoneum (14; 15.2%), mediastinum (15; 16.3%) and pelvis (5;
5.4%). A small minority of patients had GCTs in other locations (n-17;
18.5%) like vagina, maxilla, orbit and the parapharynx. While 53
(57.6%) patients were treatment-naive, 23 (25%) underwent surgical
resection and 16 (17.4%) underwent biopsy prior to presentation.
Eighteen patients with intra-abdominal GCTs (sixsacrococcygeal,
eightpelvic and four retroperitoneal) presented with features of
obstructive uropathy of varying severity, necessitating urgent
procedural intervention in four of them (ureteral stenting in 2 and
nephrostomy in 2 patient). Eighteen patients (19.5%) received JEb
instead of PEb because of underlying renal dysfunction. Additionally, 14
patients (15.2%) received JEb for the first two cycles before
continuing on PEb. Two patients had involvement of the sacral nerve
plexus with neurogenic bladder and one of them had long-standing
neurological complications including clubfoot. The 5-yr-EFS and OS of
extragonadal tumors at a median follow-up of 45.9 ± 36.1 months was
69.0% & 70.7% respectively.