Focal and craniospinal irradiation for patients with intracranial germinoma and patterns of failure

Abstract

Disease Overview: Acute myeloid leukemia (AML) results from accumulation of abnormal immature cells in the marrow. These cells interfere with normal hematopoiesis can escape into the blood and infiltrate lung and CNS. The most common cause of death is bone marrow failure. It is likely that many different mutations and/or epigenetic aberrations can produce the same disease, with these differences responsible for the very variable response to therapy, which is AML's principal clinical feature. Diagnosis: This rests on demonstration that the marrow or blood has >20% blasts of myeloid lineage. Blast lineage is assessed by multiparameter flow cytometry with CD33 and CD13 being surface markers typically expressed by myeloid blasts. It should be realized that clinical/prognostic considerations, not the blast % per se, should be the main factor determining how a patient is treated. Risk stratification: Two features determine risk: the probability of treatment‐related mortality (TRM) and, more important, even in patients aged >75 with Zubrod performance status 1, the probability of resistance to standard therapy despite not incurring TRM. The chief predictor of resistance is cytogenetics with a monosomal karyotype (MK) denoting the disease is essentially incurable with standard therapy even if followed by a standard allogeneic transplant (HCT). The most common cytogenetic finding is a normal karyotype (NK) and those of such patients with an NPM1 mutation but no FLT3 internal tandem duplication (ITD), or with a CEBPA mutation, have a prognosis similar to that of patients with the most favorable cytogenetics [inv(16) or t(8;21)] (60–70% cure rate). In contrast, NK patients with a FLT3 ITD have only a 30–40% chance of cure even after HCT. Accordingly analyses of NPM1, FLT3, and CEBPA should be part of routine evaluation, much as is cytogenetics. Risk is best assessed considering several variables simultaneously rather than, for example, only age. Risk‐adapted therapy: Patients with inv(16) or t(8;21) or who are NPM1+/FLT3ITD− can receive standard therapy (daunorubicin + cytarabine) and should not receive HCT in first CR. It seems likely that use of a daily daunorubicin dose of 90 mg/m2 will further improve outcome in these patients. There appears no reason to use doses of cytarabine > 1 g/m2 (for example, bid × 6 days), as opposed to the more commonly used 3 g/m2. Patients with an unfavorable karyotype (particularly MK) are unlikely to benefit from standard therapy (even with dose escalation) and are thus prime candidates for clinical trials of new drugs or new approaches to HCT; the latter should be done in first CR. Patients with intermediate prognoses (for example, NK and NPM and FLT3ITD negative) should also receive HCT in first CR and can plausibly receive either investigational or standard induction therapy, with the same prognostic information about standard therapy leading one patient to choose the standard and another an investigational option. Am. J. Hematol. 87:90–99, 2012. © 2011 Wiley Periodicals, Inc.

Optimal treatment strategy for intracranial germ cell tumors: a single institution analysis

“…1,4,12,19,20,24,32 Tumor control and excellent functional outcome rates were achieved in 90% of 16 patients with pure germinoma treated with cisplatin-based chemotherapy, followed by 24 Gy of focal radiation therapy to the tumor site for solitary germinoma, the whole ventricle for multifocal germinoma, and the craniospinal axis for disseminated germinoma. 1 However, the combination of cisplatin-based chemotherapy and 24-30 Gy of focal radiation therapy to the primary tumor site with 1-2 cm margins resulted in an increased recurrence rate up to 20-44%.…”

“…1 However, the combination of cisplatin-based chemotherapy and 24-30 Gy of focal radiation therapy to the primary tumor site with 1-2 cm margins resulted in an increased recurrence rate up to 20-44%. 24,32 In addition, we previously reported a case of recurrent intracranial germinoma outside the initial radiation field with progressive malignant transformation. 16 Therefore, neoadjuvant reduced-field radiation therapy not covering the whole ventricle may be associated with increased risk of recurrence, and radiation therapy to cover the whole ventricle is essential for longterm tumor control.…”

Recent advances in molecular biology and treatment strategies for intracranial germ cell tumors

“…Fouladi et al [45] reported there were similar effects of CSI on the regimen of carboplatin and etoposide chemotherapy (2-3 cycles) plus local field radiotherapy (total dose: 25-35 Gy) with a similar 5-year survival rate. Nguyen et al [46] reported the same 5-year survival rate of both CSI and chemotherapy followed by local field radiotherapy. However, this combined therapy was found to be co-related with spinal tumor recurrence.…”

Late Recurrence of a Pineal Germinoma 14 Years after Radiation and Chemotherapy: A Case Report and Review of the Literature

“…Overall survival at 5 years is 90% [1,2,3,12]. The optimal treatment of IG is still a matter of debate [13,14].…”

“…Intracranial germinomas (IG) are rare tumors which at first diagnosis are highly curable with radiotherapy alone or a combination of radiotherapy and chemotherapy [1,2,3]. Recurrence and dissemination are seen in about 10-20% of cases, in the vast majority occurring within the first 2 years after diagnosis, whereas late recurrences are rare events [4,5,6,7].…”