Germinoma medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Simrat Sarai, M.D. [2]

Overview

Therefore, radiation therapy remains an important and integral part of therapy for patients with CNS GCTs.

Medical Therapy

Radiation

• Germinomas are highly responsive to radiation therapy; however NGGCTs are less radiosensitive than pure germinomas.
• Since studies comparing full-dose craniospinal irradiation CSI with reduced-volume radiation, whether whole-ventricular or whole-brain have shown no significant difference in the pattern of relapse in germinomas, therefore, CSI is no longer used for localized germinomas.
• Trials to determine the best regimen for radiation therapy are still ongoing.
• Since patients who received radiation therapy to the localized tumor alone had a higher rate of recurrence, radiation therapy to include the whole ventricles is recommended.
• The majority of clinicians advocate a boost to the primary tumor bed in order to prevent local recurrence.
• Studies to prove the efficacy of radiation therapy alone versus neoadjuvant chemotherapy followed by response-based radiotherapy are currently under way. The use of intensive chemotherapy alone without radiation therapy has proven less effective compared with chemotherapeutic regimens and radiation therapy together.
• In patients with pure CNS germinomas, no deterioration in neurocognitive function and no compromise in outcome was found when chemotherapy was administered followed by reduced dose radiation therapy.

Chemotherapy

In patients with germinomas, chemotherapy has been recently added to the treatment regimen in order to permit the use of a lower radiation dose, thereby reducing the long-term morbidity associated with radiation therapy while maintaining the excellent survival rates.[5, 8, 9, 57, 51, 60] Germinomas are chemosensitive, especially to platinum-based agents.[76] The current recommendation is to proceed with neoadjuvant therapy prior to lower-dose and lower-volume radiation therapy.

Patients with NGGCTs have an inferior outcome compared with patients with germinomas. Combined therapy with neoadjuvant and adujant chemotherapy with radiation therapy is intended to improve outcome.[9, 24, 33, 60, 77] The increase in survival seen with combination therapy has made chemotherapy an integral part of treatment for NGGCTs.[25, 62, 67, 78]

The role of full-dose CSI is controversial in patients with localized NGGCTs. Results from the forthcoming Children’s Oncology Group (COG) trial for children with localized NGGCT may clarify this issue. In a proposed trial by the COG, children with localized NGGCT who attain complete response to chemotherapy alone or chemotherapy and second-look surgery will not receive CSI; however, they will receive radiation to the whole ventricle plus a tumor boost.

As with gonadal germ cell tumors, the agents that to date have shown the best activity against CNS GCTs are cisplatin, etoposide, vinblastine, bleomycin, and carboplatin.[51] Ifosfamide and cyclophosphamide are also used.[57]

Therapy may be based on classification of CNS GCTs into good prognosis (pure germinomas, mature teratoma); intermediate prognosis (germinoma with high bHCG, extensive multifocal germinoma, immature teratoma, teratoma with malignant transformation, mixed tumors composed of germinoma or teratoma); and poor prognosis (choriocarcinoma, yolk sac tumor, endodermal sinus tumor, mixed tumors composed of choriocarcinoma, yolk sac tumor, and endodermal sinus tumor).[62, 67]

Some European groups classify CNS GCTs into secreting and nonsecreting based on the presence or absence of tumor markers, including bHCG and alpha-fetoprotien in the CSF and serum.[79]

Patients with relapsed or progressive disease, especially those with NGGCTs, have a poor prognosis. High-dose chemotherapy followed by autologous stem cell transplant may be effective in this group of patients.[80]

Stage or Tumor Type	Treatment Options
Newly diagnosed childhood germinomas	Radiation therapy Neoadjuvant chemotherapy followed by response-based radiation therapy
Newly diagnosed childhood teratomas	Surgery Adjuvant therapy, for patients who had a subtotal resection (controversial): Focal radiation therapy Chemotherapy Stereotactic radiosurgery
Newly diagnosed childhood nongerminomatous GCTs	Chemotherapy followed by radiation therapy Surgery
Recurrent childhood CNS GCTs	Chemotherapy followed by radiation therapy High-dose chemotherapy with stem cell rescue

Drug name	Mechanism of action
Cisplatin	Cisplatin inhibits DNA synthesis and, thus, cell proliferation by causing DNA cross-links and denaturation of double helix
Bleomycin	Bleomycin is a glycopeptide antibiotic that inhibits DNA synthesis. For palliation in management of several neoplasms.
Etoposide, VP-16	Inhibits topoisomerase II and causes DNA strand breakage, causing cell proliferation to arrest in late S or early G2 phase of cell cycle.
Cyclophosphamide	It is chemically related to nitrogen mustards. As alkylating agent, mechanism of action of active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells
Desmopressin acetate	Increases cellular permeability of collecting ducts, resulting in reabsorption of water by kidneys.

References

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