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      Drugs & Diseases > Oncology

      Central Nervous System Germinoma Treatment & Management

      Updated: Mar 25, 2021
      • Author: Amani A AlKofide, MD; Chief Editor: Herbert H Engelhard, III, MD, PhD, FACS, FAANS  more...
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      Treatment

      Medical Care

      Radiation therapy

      In the past, patients with imaging findings typical of central nervous system (CNS) germinoma were treated empirically with radiation therapy. [2] This approach has largely been abandoned, since current stereotactic biopsy techniques permit histological diagnosis with minimal risk of morbidity. Identification of the histological elements of CNS germ cell tumors (GCTs) is important in determining the most appropriate therapeutic strategy, because the different histological types vary in their sensitivity to radiation. [12, 80, 81]

      Germinomas are highly responsive to radiation therapy [82, 83, 84] ; a complete response rate with a 5-year survival of more than 90% is seen with radiation therapy alone. [2, 85] Nongerminomatous GCTs (NGGCTs) are less radiosensitive than pure germinomas, with an overall 5-year survival of 30-50%.

      Full-dose craniospinal radiation (CSI) was traditionally employed for patients with pure germinomas. Side effects of CSI may be significant. Studies comparing CSI with reduced-volume radiation, whether whole-brain or whole-ventricular, have shown no significant difference in the pattern of relapse in germinomas. [12, 7, 86, 87, 88] Therefore, CSI is no longer used for localized germinomas. [86, 89]

      Currently, effective therapy uses whole-ventricular irradiation and chemotherapy to reduce the radiation therapy dose. [90] Because radiation exposure of the temporal ventricular horns and hippocampi may lead to long-term poor cognitive function, Yan et al reviewed the outcome in pediatric cases in which the temporal ventricular horns were excluded from ventricular clinical target volumes. Exclusion resulted in significant dose sparing to the hippocampi and temporal lobes, while clinical outcomes remained excellent, with no deaths and no temporal ventricular horn failures. However, long-term neuropsychological studies are required to confirm the benefit. [91]

      Trials to determine the best regimen for radiation therapy are ongoing. [85, 92] Currently, patients with localized or multifocal disease may receive 24 Gy to the whole-ventricular system and a 21-Gy boost to all measurable disease.

      Radiation therapy to include the whole ventricles appears to be essential in controlling disease. Higher rates of recurrence have been documented in patients who received radiation therapy to the localized tumor alone. [83, 93]

      Most experts advocate a boost to the primary tumor bed in order to prevent local recurrence; 45 Gy appears to be a satisfactory upper dose limit. [69, 94, 95, 96] Patients with disseminated disease may receive 24 Gy to the craniospinal axis. [83, 92, 97]

      Studies of radiation therapy alone versus neoadjuvant chemotherapy followed by response-based radiotherapy have shown that chemotherapy followed by reduced-dose radiation therapy appears to be effective in patients with pure CNS germinomas, with no deterioration in neurocognitive function and no compromise in outcome. [11, 79, 83, 86, 88, 98, 99, 100]

      A report from a prospective, multinational nonrandomized trial in children and adults with intracranial germinoma (the SIOP CNS GCT 96 study) further supports the results of previous trials. This study used chemotherapy followed by reduced-dose CSI of 24 Gy CSI and a 16-Gy tumor boost for patients with both localized and metastatic disease, with a 5-year progression-free survival of 98%. [101]

      The use of intensive chemotherapy alone without radiation therapy has proven less effective, resulting in inferior outcome compared with chemotherapeutic regimens and radiation therapy together. [102] Therefore, radiation therapy remains an important and integral part of therapy for patients with CNS GCTs.

      Chemotherapy

      In patients with germinomas, chemotherapy has been added to the treatment regimen 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. [30, 11, 12, 81, 69, 85] Germinomas are chemosensitive, especially to platinum-based agents. [103] 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. [12, 79, 31, 85, 104] The increase in survival seen with combination therapy has made chemotherapy an integral part of treatment for NGGCTs. [7, 87, 94, 105]

      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 (ACNS1123) may clarify this issue. In this trial by the COG, children with localized NGGCT who attain complete response to chemotherapy alone or chemotherapy and second-look surgery will receive radiation to the whole ventricle plus a tumor boost (3-dimensional conformal radiation therapy) rather than CSI.

      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. [69] Ifosfamide and cyclophosphamide are also used. [81]

      Patients with relapsed or progressive disease, especially those with NGGCTs, have a poor prognosis. High-dose chemotherapy followed by autologous stem cell transplantation may be effective in this group of patients. [106]

      Next:

      Surgical Care

      Currently the recommended practice is to acquire a tissue biopsy sample, with the exception of patients who have a characteristic elevation in tumor markers and in whom surgical intervention may lead to significant sequelae. [30, 82, 31, 69, 94]

      Surgical treatment of CNS GCTs varies according to the tumor type. Germinomas carry a relatively excellent prognosis and management has therefore focused on reducing morbidity. Partial and gross total resection of germinomas has no proven benefit and may lead to neurological or endocrinological deterioration. Therefore, most neurosurgeons limit surgical intervention to biopsy and instead treat these patients with radiation and chemotherapy. [11, 12, 86]

      Patients with choriocarcinoma have an increased tendency to hemorrhage; current recommendation is for early and radical surgery.

      Patients with NGGCTs have poor long-term survival, and surgery for these patients is aimed at improving outcome. Reduction of tumor burden by partial resection is often an option when removal of all tumor tissue is impossible. Adjuvant radiation therapy and chemotherapy are often incorporated in the treatment plan. [79, 107, 104]

      Conflicting results may occur, in particular with small surgical samples that may not be representative, such as histological diagnosis of pure germinoma and raised alpha fetoprotein levels, in which case the patient should be treated more aggressively than those with pure germinoma with normal CSF/serum marker levels. Patients with a tissue diagnosis of NGGCT should be treated as such regardless of CSF/serum tumor marker levels.

      Patients presenting with obstructive hydrocephalus may require a ventriculoperitoneal shunt.

      In patients who have had an incomplete response to initial chemotherapy, second-look surgery may be performed to remove the residual tissue and permit its histological verification. The remaining tissue may contain malignant elements; however, it may consist of fibrosis, necrosis, or a mature teratoma—the so-called growing teratoma syndrome. [69, 94] The growing teratoma syndrome is characterized by enlarging tumor mass during or after chemotherapy in the presence of normal or declining tumor markers. Surgical resection of the tumor is considered curative. [80, 108]

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      Consultations

      Neurology and neuropsychology

      Patients should undergo preoperative, postoperative, and followup neurological assessment, utilizing tools such as the following:

      • Karnofsky Performance Scale (KPS)
      • Modifed Rankin Scale (m-RS)
      • Neurological Performance Scale (MRC)
      • Cognitive Performance Scale (CPS)
      • Barthel Activities of Daily Living (ADL) Index

      The performance assessment should be consistent throughout the patients course.

      Neuropsychological assessment should be provided—especially for adolescents, to ensure proper schooling and adjustment.

      Endocrinology

      Patients with CNS GCTs may have a range of endocrine dysfunctions, including diabetes insipidus, hypothyroidism, precocious or delayed puberty, sexual dysfunction, growth failure, adrenal crises, and panhypopituitarism. Proper monitoring of hormone levels and electrolytes is essential. Lifelong hormonal replacement may be required for most of these patients.

      Ophthalmology

      Disturbance in vision is a common presenting feature. Evaluation by an ophthalmologist will identify the visual deficit.

      Audiometry

      Audiogram studies should be performed, especially in patients expected to receive radiation therapy and ototoxic agents—specifically, cisplatin.

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