Advanced Malignant Germ Cell Tumors Research Articles

Neo-adjuvant chemotherapy in the treatment of advanced malignant germ cell tumors of ovary

ObjectiveIn order to preserve fertility, we attempted neo-adjuvant chemotherapy (NACT) in patients of malignant ovarian germ cell tumor (MOGCT) with advance and bulky disease. Patients and methodsBetween January 1988 and December 2009, 23 patients received NACT. Patient's median age was 19years, ranging from 14 to 28years. FIGO stages III — 20 and IV — 3. Histology subtypes were: dysgerminoma, n=14, mixed GCT, n=6 and 3 had endodermal sinus tumor. Patients were planned for four cycles of BEP (bleomycin, etoposide and cisplatin) chemotherapy followed by fertility sparing surgery (unilateral salpingo-oophorectomy+omentectomy±lymphadenectomy). ResultsFollowing NACT — 21 patients responded; complete (CR) — 16 and partial response (PR) — 5. One patient progressed and another was lost to follow-up after 2cycles. 18 of 21 responders underwent surgery; 13/18 had pathological CR, 5/18 had residual disease and achieved CR following 2 more cycles of BEP. 3 patients refused for surgery; 2 relapsed at 9 and 12months, and achieved second CR following salvage chemotherapy and surgery, third patient continues to be disease-free. Currently, 21 of 23 patients are alive and disease-free at a median follow-up of 74months. 18/21 patients have resumed menstruation and 10 eligible patients have delivered 13 full term healthy babies. These results are comparable to patients with advanced disease (n=43) treated with standard approach (initial surgery and adjuvant chemotherapy) during the same period. ConclusionNACT followed by fertility sparing surgery could be a reasonable option for patients of advanced MOGCT, not suitable for optimal cyto-reduction.

Is there a place for neoadjuvant chemotherapy in the management of advanced malignant germ cell tumors of ovary?

5079 Background: There is limited data on the role of neoadjuvant chemotherapy (NACT) in advanced malignant ovarian germ cell tumors (MOGCT).We attempted NACT in 20 Pts of advanced MOGCT who were considered high risk for surgery (very poor general health; ECOG performance status, 3-4) in order to preserve fertility. Methods: Between 1988 and December 2009, 20 of 211 patients with MOGCT were considered unsuitable for exploratory laparotomy because of their high risk status. Pts median age was 19 yrs, ranging from 14-28 yrs. All had stage III (n=17) or IV (n=3) disease. Diagnosis was confirmed by FNAC /Biopsy & baseline tumor marker levels. 11 pts had dysgerminoma, 6 had mixed subtype & 3 had endodermal sinus tumor (EST). All were planned for four cycles of BEP chemotherapy followed by fertility sparing surgery (U/L salpingo-oophorectomy + omentectomy ± Lymphadenectomy). Results: 18 Pts were evaluable for treatment response & outcome. One Pt died after 1st cycle of CT due to progressive disease and another Pt was lost to FU after 2 cycles. Post 4 cycles of chemotherapy, 18 responded: CR-13, PR-5. 15 Pts underwent surgery with pathological CR in 13/15 (86.6%); 2 Pts had residual disease, both of them achieved CR following 2 cycles of salvage chemotherapy. Remaining three Pts refused for surgery; 2 out of 3 relapsed at 9 and 12 months, both achieved CR with salvage chemotherapy and subsequent fertility sparing surgery; third Pt continues to be alive and in good health. Currently 18 of 20 patients are alive and disease free and in one status is unknown at a median follow-up of 48 months (range: 12-96 months). All of them have resumed menstruation and 3 eligible Pts have delivered full term healthy babies. Conclusions: NACT followed by fertility sparing surgery is an effective treatment strategy for patients of advanced MOGCT who are high risk candidates for surgery.

Chemotherapy for the Treatment of Children and Adolescents With Malignant Germ Cell Tumors

Chemotherapy for the Treatment of Children and Adolescents With Malignant Germ Cell Tumors

Fertility-preserving treatment for advanced malignant germ cell tumors of the ovary

We retrospectively studied 26 patients with stage Ic or greater malignant germ cell tumors of the ovary. Sixteen of the 26 underwent fertility-preserving treatment and 10 underwent total hystero-oophorectomy. There were 3 deaths in each group, but none among the stage Ic cases. The survival curves for stage II to IV disease did not significantly differ in the two groups. Seven patients in the fertility-preserving group were married, and had children. All patients in the hystero-oophorectomy group remained single except for one who was married before surgery. These results suggest that fertility-preserving treatment should be offered even in advanced cases.

Salvage treatment in male patients with germ cell tumours

The outcome of salvage treatment was reviewed in 55 patients relapsing during or after their primary chemotherapy for advanced malignant germ cell tumours. Fifty-two patients had been given cisplatin-based chemotherapy as their primary treatment, whereas three patients had received carboplatin-based chemotherapy. The median time to relapse was 2 months (range: 0-96 months) from discontinuation of the primary treatment. Two patients underwent radical surgery only, and one patient had radiotherapy to a brain metastasis as his only curatively intended salvage treatment. Six patients did not receive any treatment for their recurrent malignancy (refusal, terminal condition) except for purely palliative measures. The disease-free survival for the total group was 27% at 5 years. Complete response to primary treatment lasting for > or = 6 months was the only parameter which significantly predicted a favourable outcome (45% 5 year disease-free survival in 12 eligible patients).

High-dose cis-platinum combination chemotherapy in advanced nonseminomatous malignant germ cell tumours with emphasis on nephrotoxicity

High-dose cis-platinum treatment (180 mg/m2 per cycle) in combination with VP16 and bleomycin was given to 14 patients with highly advanced nonseminomatous malignant germ cell tumours (total: 31 cycles). Cis-platinum was administered in infusions of 0.9% NaCl given daily for 3 days with 3-week intervals. An intensive hydration regimen (71 NaCl/day) provided a urinary output of at least 1000 ml/4 h. The response and side effects were evaluated. Ultimately 11 of 12 patients evaluable for treatment effect were rendered tumour-free and are alive with NED. All 14 patients were evaluable for toxicity; 2 developed life-threatening lung edema during the initial prehydration period and did not continue the high-dose cis-platinum schedule. After one to four cycles of high-dose cis-platinum treatment the 131I-Hippuran clearance was reduced by 28%. Decreased kidney function evaluated by 131I-Hippuran clearance was the reason for discontinuation of treatment in 5 patients. Patients with ureteric obstruction represented a high-risk group for reduction of kidney function. High-dose cis-platinum therapy is an intensive treatment demanding a high level of investment of resources, which has promising response rates in patients with highly advanced malignant germ cell tumours. Short-term clinically significant reduction of the kidney function can be avoided by intensive hydration of the patient.

High complete response rate in children with advanced germ cell tumors using cisplatin-containing combination chemotherapy.

A consecutive series of 13 children (five girls) with advanced malignant germ cell tumors (MGCTs) were treated with between four and seven (median, six) courses of cisplatin, bleomycin, and either vinblastine (BVP) or VP-16 (BEP). There were seven gonadal primaries (four testis, three ovary) and six at extragonadal sites (three sacrococcyx, two thoracic, one extradural). Total or subtotal removal of primary tumor was carried out in nine patients at diagnosis and two others after some chemotherapy. Clinical complete remission (CR) was achieved in nine of ten patients with measurable disease and serum markers returned to normal in all 13 patients. Eleven remain disease-free 17 to 48 months (median, 28 months) after diagnosis. One patient (stage IV sacrococcygeal tumor) relapsed at the primary site 3 months after completing treatment, but is disease-free after further surgery, radiotherapy, and chemotherapy. Serial glomerular filtration rates were performed during treatment. Audiometry and pulmonary function tests were carried out where possible. Toxicity led to alteration of drug scheduling in two cases, but there were no permanent clinical renal, auditory, or pulmonary sequelae. These encouraging results confirm that MGCTs in children are as responsive as those in adults to cisplatin-containing chemotherapy and indicate that they may be as curable. The regimens are relatively well-tolerated and, with close monitoring, clinically significant toxicity should be avoidable.

Multi-modality treatment of advanced malignant germ cell tumours in males. I. Experience with cis-platinum-based combination chemotherapy.

Three-weekly cis-platinum-based combination chemotherapy with or without subsequent surgery and/or radiotherapy resulted in a 58% 3-year-survival in 79 patients with advanced malignant germ cell tumours. Poor risk factors were relapse after previous chemotherapy, retroperitoneal bulky disease, liver metastases and extremely high serum levels of AFP, beta-HCG, and LDH. Patients with pure seminoma had a high curation rate. The overall toxicity was acceptable. Cis-platinum-based chemotherapy is at present the most effective cytotoxic treatment for patients with advanced malignant germ cell tumours. The relatively low survival rate in poor-risk patients necessitates more aggressive primary chemotherapy in this subgroup of patients.

Multi-modality treatment in males with advanced malignant germ cell tumours. II. Experience with surgery and radiotherapy following cis-platinum-based chemotherapy.

After chemotherapy with cis-platinum, vinblastine and bleomycin, 33 surgical procedures were performed in 29 patients with advanced malignant germ-cell tumours. The tumour masses could be completely resected macroscopically in 26 patients. Histology of the operation specimens showed fibrosis/necrosis (9 specimens), mature teratome (13 specimens) and vital malignant tumour (11 specimens). Patients with fibrosis/necrosis or completely resected mature teratoma had an excellent prognosis, whereas only 5 of the 11 patients with vital malignant tumour survived in spite of second-line treatment with chemotherapy/radiotherapy. Preoperatively elevated serum levels of AFP, beta-HCG and/or LDH indicated the presence of residual vital malignant germ cell tumour. Eight of 14 patients were rendered tumour-free by radiotherapy given as second- or third-line treatment. In general, tumour masses, remaining after cis-platinum-based induction chemotherapy should be resected as completely as possible even in the case of mature teratoma or fibrosis/necrosis. Radiotherapy should be considered as second- and third-line treatment in selected patients.