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Little is known about pseudoprogression in brain tumours other than gliomas. A 9-year-old male child with a pineal teratoma/germinoma underwent surgical resection followed by adjuvant chemo-radiotherapy. The magnetic resonance imaging scan 4 months post-radiotherapy showed a contrast-enhancing lesion within the surgical cavity suspicious of recurrence. These radiological findings subsequently resolved without any specific intervention. The child continues in remission 2 years post-treatment. This case illustrates the occurrence of pseudoprogression post-radiotherapy in intracranial GCT and highlights an unmet need for greater implementation of functional imaging techniques in paediatric neuro-oncology to avoid undue discontinuation of effective treatments or inappropriate enrolment in clinical trials., (© 2020 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals, Inc.)

Craniospinal irradiation is standard radiotherapy (RT) for localized intracranial nongerminoma germ cell tumors (NGGCT). Given its toxicity, there is interest in using smaller fields. We examined outcomes of NGGCT patients receiving reduced-volume RT at a single institution. Records of 16 patients who received reduced-volume RT as part of definitive treatment between 1996 and 2016 were reviewed. Median age at presentation was 10.8 years (range 4.6-41.0 years). Ten patients had pineal tumors and 6 had suprasellar tumors. All received chemotherapy and 9 patients received second-look surgery thereafter. RT volume was tumor-only to a median of 54 Gy (range 50.4-54 Gy) in 3 patients and whole-ventricle irradiation to a median of 30.6 Gy (range 30.6-36 Gy) with a boost to 54 Gy in 13 patients. Median follow-up was 4.1 years (range 1.9-19.3 years). Three patients recurred locally at a median 9.9 months (range 9.6-10.6 months) after diagnosis, and one of these developed leptomeningeal relapse after 30 months. One patient expired from disease 2.6 years post-diagnosis and another due to stroke 19.3 years post-diagnosis. Fourteen patients are alive with no evidence of disease. Kaplan-Meier estimates of the 4-year overall survival and failure-free survival are 92% (95% confidence interval [CI], 57-99%) and 81% (95% CI 53-94%), respectively. Excellent disease control was observed in these patients with no initial relapses outside of these RT fields. The results of ACNS1123 may better delineate patterns of failure and identify subgroups likely to benefit from this approach.

Pineal tumor management in pediatric patients must be based on close co-operation between oncologists, surgeons, radiation oncologists, neurologists, ophthalmologists, and endocrinologists. Radiation therapy (RT) remains critical in most situations and should be assessed as soon as the diagnosis is made, in order to optimize the radiation technique. This paper will focus on RT modalities, indications, as well as modalities in main pediatric pineal tumors (germ cell tumors and pineal parenchyma tumors). RT modalities are presently being debated and new RT techniques (intensity-modulated RT, proton therapy etc.) that are now available for pineal lesions need to be evaluated. Radiation strategies are also controversial for germ cell tumors: cranio-spinal radiation versus chemotherapy followed by focal radiation, which also requires discussion., (Copyright © 2015. Published by Elsevier Masson SAS.)

Germ cell tumours (GCT) are a relatively common malignancy in men aged 15-35 years. They occur most frequently in the gonads, but 3-5% have extragonadal origin, mainly in the pineal gland, neurohypophysis, mediastinum and retroperitoneum. Although intracranial germinomas may present with synchronous midline lesions, development of metachronous testicular germ cell primaries seems to be extremely rare, and confirmed dissemination of intracranial GCT to the testes has never been reported. We report the case of a 32-year-old man, with previously treated pineal germinoma at age 16 years, who later developed mixed GCT of the left testis.

Purpose of Review: Pineal tumors are rare in children, with pineoblastoma and germ cell tumors (GCTs) being the most common. Here we discuss recent advances in treatment and controversies in the management of these tumors., Recent Findings: There is significant heterogeneity in the clinical behavior of pineoblastoma in children. We will discuss differences in outcome of children with pineoblastoma who are less than and greater than 3 years of age, and between pineoblastoma and nonpineal supratentorial primitive neuro-ectodermal tumors when treated with multiple different strategies. Significant controversies exist in the treatment of GCTs as well, including the levels of tumor markers in the blood and cerebrospinal fluid that are required to establish without biopsy the diagnosis of a GCT, the role of surgery in GCTs and the optimal treatment for germinomas as well as mixed malignant GCTs., Summary: Although pineoblastoma in infants and very young children still remains a therapeutic challenge, significant progress has been made in the treatment of pineal GCTs with treatment strategies using a combination of chemotherapy and reduced dose and volume irradiation, resulting in increased survival rates and reduced long-term morbidity.

Purpose: To compare the sparing potential of cerebral hemispheres with intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) for whole-ventricular irradiation (WVI) and conventional whole-brain irradiation (WBI) in the management of localized central nervous system germ cell tumors (CNSGCTs)., Methods and Materials: Ten cases of patients with localized CNSGCTs and submitted to WVI by use of IMRT with or without a "boost" to the primary lesion were selected. For comparison purposes, similar treatment plans were produced by use of 3D-CRT (WVI with or without boost) and WBI (opposed lateral fields with or without boost), and cerebral hemisphere sparing was evaluated at dose levels ranging from 2 Gy to 40 Gy., Results: The median prescription dose for WVI was 30.6 Gy (range, 25.2-37.5 Gy), and that for the boost was 16.5 Gy (range, 0-23.4 Gy). Mean irradiated cerebral hemisphere volumes were lower for WVI with IMRT than for 3D-CRT and were lower for WVI with 3D-CRT than for WBI. Intensity-modulated radiotherapy was associated with the lowest irradiated volumes, with reductions of 7.5%, 12.2%, and 9.0% at dose levels of 20, 30, and 40 Gy, respectively, compared with 3D-CRT. Intensity-modulated radiotherapy provided statistically significant reductions of median irradiated volumes at all dose levels (p = 0.002 or less). However, estimated radiation doses to peripheral areas of the body were 1.9 times higher with IMRT than with 3D-CRT., Conclusions: Although IMRT is associated with increased radiation doses to peripheral areas of the body, its use can spare a significant amount of normal central nervous system tissue compared with 3D-CRT or WBI in the setting of CNSGCT treatment., (Copyright 2010 Elsevier Inc. All rights reserved.)

The histopathological entity 'germ cell tumor' (GCT) encompasses a number of histological subtypes. Pineal GCTs can be grossly divided into three categories: those with a good, intermediate, and poor prognostic. Germinoma and mature teratoma are curable and classified into the good prognostic group, whereas embryonal carcinoma, yolk sac tumor, and other highly malignant neoplasms leave patients with a dismal prognosis. There are other types of GCT that have an intermediate prognosis, such as immature teratoma. Only mature teratomas are curable by surgical resection alone; the other types require adjuvant therapy. To plan a surgical strategy, then eurosurgeon has to acquire enough knowledge of the effect of adjuvant therapies and biological behavior of the GCTs. Germinoma can be cured by low-dose radiotherapy in combination with chemotherapy, and nowadays needs only to be biopsied. Other tumors, such as highly malignant tumors need a sophisticated combination therapy that includes surgery, craniospinal radiation therapy, and intensive chemotherapy. An appropriate neoadjuvant therapy prior toradical surgical removal will remarkably reduce the surgical risk. The goal of treatment should be tightly focused on the reduction of posttreatment sequelae, including surgical morbidity, and not on a complete microsurgical resection., (Copyright (c) 2009 S. Karger AG, Basel.)

Although radiation therapy (RT) is essential to the management of intracranial germ cell tumors, the ideal radiation dose and field remain controversial. For the treatment of germinoma, whole central nervous system radiation, which was once the standard RT field, is being replaced by whole ventricle (WV) field radiation for localized disease. The use of induction chemotherapy has been expected to further reduce the RT field and dose; however, use of a localized field smaller than the WV field has resulted in a higher recurrence rate. Therefore, the WV field should be considered appropriate even after induction chemotherapy. With regard to the radiation dose to the primary tumor site, it can be reduced to 40-45 Gy in RT alone. The further reduction of the radiation dose when using a combination of chemotherapy and RT is yet to be determined. Unlike germinomas, nongerminomatous germ cell tumors, with the exception of mature teratomas, are refractory to conventional RT. The whole central nervous system field should thus be used for all but immature teratomas. Given that local progression is the primary pattern of recurrence even after effective induction chemotherapy, RT dose increase through the use of modern techniques, including stereotactic irradiation and intensity-modulated RT, should be investigated., (Copyright (c) 2009 S. Karger AG, Basel.)

Background: This Phase II study was designed to determine response to chemotherapy and survival after response-based radiation (RT) in children with CNS germ cell tumors., Procedure: Children with germinomas and normal markers received cisplatin 100 mg/m(2) + etoposide, alternating with vincristine + cyclophosphamide (CPM) 2 g/m(2)/d, for four cycles. Children with nongerminomatous tumors or with abnormal markers received doubled doses of cisplatin and CPM. For germinoma patients in complete response (CR), RT was decreased from 50.4 to 30.6 Gy. High-risk patients received neuraxis RT: 50.4 Gy local + 30.6 Gy neuraxis in CR; 54 Gy local + 36 Gy if less than CR., Results: Of 12 germinoma patients, 4 had cerebrospinal fluid (CSF) human chorionic gonadotropin (HCG) 6.9-21 mIU/ml. Of 14 nongerminomatous patients, HCG in serum or CSF was >50 mIU/ml in 9, alpha-fetoprotein (AFP) abnormal in 9. Four germinoma patients attained CR, six PR, one SD, one not evaluable after resection. Two nongerminomatous patients had CR, three PR, three SD, one PD, four not evaluable after resection; one inadequately treated patient had progressive disease (PD). Both PD patients died; one SD patient died during a seizure. Eleven germinoma patients are PF at median 66 months; one patient in CR refused RT, had PD at 10 months, received RT, and was PF at 56 months. Eleven of 14 nongerminomatous patients were PF at median 58 months., Conclusion: Response (germinoma, 91%; nongerminomatous, 55%) and survival are encouraging after this regimen plus response-based RT., ((c) 2006 Wiley-Liss, Inc.)

This retrospective study was conducted to evaluate local control and overall survival after radiotherapy for patients with intracranial germ cell tumors and to investigate the influence of irradiated field on treatment outcome. Thirty-two patients with surgically confirmed or suspected primary intracranial germ cell tumors (GCT) treated at the Division of Therapeutic Radiology and Oncology, Chiang Mai University, Chiang Mai, Thailand between January 1988 and December 1999 were reviewed Seven patients were not included in the analysis of treatment outcome and survival due to incompleteness of radiation treatment or death before the end of treatment. The median follow up time of 39.5 months (range from 2.3 months to 136.1 months). Median age at diagnosis was 16.5 years with 23 males and 9 females. Patients were irradiated to the primary tumor with an adequate margin in 7 patients, to the whole brain with a cone down boost in 8 patients. Craniospinal irradiation (CSI) was performed in 10 patients. For the 25 evaluable patients, 5 year overall survival was 86.4%. Five-year disease free survival was 72.9%. Five year overall survival rates were 83.1% and 90.0% for the germinoma and nonbiopsied group. (p-value = 0. 6052). Routine prophylactic CSI was not given with a spinal only failure rate of 33.3%. Five-year overall survival were 85.7%, 87.5%, 85.7% for CSI, whole brain irradiation with boost and local field irradiation (p-value = 0.9037). Five-year disease free survival were 85.7%, 72.9%, 85.7% for CSI, WBRT, and local field (p-value = 0. 6403). This retrospective study suggests that definitive radiation therapy is effective in controlling germinoma, and cure rates are excellent with irradiation alone. Craniospinal irradiation can eliminate the risk of relapse especially in patients who had incomplete diagnostic craniospinal evaluation.

Unlabelled: Malignant non-germinomatous intracranial germ cell tumors (MNGGCTs) are a heterogenous group of neoplastic lesions. Their treatment concept follows a multimodal concept that may include tumor resection for local tumor control, craniospinal irradiation to cover leptomenigeal tumor spread and chemotherapy to eliminate systemic tumor dissemination. A Platinum-based chemotherapy proven to be highly effective in testicular and non-testicular malignant germ cell tumors in adults as well as in children has also been chosen for intracranial sites. While therapeutic concepts have been thoroughly evaluated for children and adolescents with extracranial nongonadal GCTs, no such detailed long term follow-up data are available for intracranial MNGGCTs. This paper reports on the long-term outcome of 41 patients with intracranial malignant non-germinomatous GCTs enrolled into the German prospective protocol MAKEI 89. The analysis focuses on the impact of surgery, radio- and chemotherapy., Patients and Methods: Between January 1989 and January 1994, 41 patients with malignant intracranial non-germinomatous GCTs were registered. Patients were compared in respect to protocol (n = 27) and non-protocol treatment (n = 14). Estimated were with chi (2) and Fisher exact test the impact of surgery, chemotherapy and irradiation on outcome., Results: The estimated (Kaplan-Meier) 5-year event free survival (EFS) of patients treated according to protocol recommendations was 0.59 +/- 0.06 (n = 27), compared to an EFS of 0.37 +/- 0.33 for patients with different treatments (n = 14) (p = 0.70, log-rank). The 5-year relapse-free survival rate (RFS) was 0.74 +/- 0.06 in protocol patients and 0.38 +/- 0.33 in non-protocol patients (median observation time of 112 months after diagnosis for surviving patients) (p = 0.14, log-rank). Surgery, complete or incomplete had no significant impact on survival (p = 0.12). Radiotherapy, in terms of craniospinal irradiation had a significant influence on survival (p = 0.035) as well as a cumulative cisplatin dose >/= 400 mg/m (2) (p = 0.002)., Conclusion: Cisplatin chemotherapy and craniospinal irradiation with tumor boost are of significant influence on long term survival in patients with MNGGCTs. The exclusion of major surgery at diagnosis using modern advances in neurosurgery or related tumor resection after neoadjuvant chemotherapy will allow a further reduction of treatment related mortality and long lasting morbidity. The analysis reveals that, given effective treatment, intracranial malignant non-germinomatous GCTs should not longer carry a poor prognosis.

The management of patients with central nervous system germ-cell tumours is evolving, and a definitive standard has not been achieved. A large amount of data indicate that radiotherapy alone results in long-term relapse free survival rates of about 90% in patients with germinoma. Various prospective trials evaluated the results of combinations of chemotherapy and reduced dose and/or volume radiotherapy. The survival rates of combined treatment approaches were similar to the rates achieved with craniospinal radiotherapy alone. Nevertheless, the relapse rates were probably higher due to the significant number of relapses that arouse outside the volume treated with radiotherapy. Additional studies are necessary to determine the appropriate radiotherapy volumes and the role of combined treatments. Chemotherapy alone results in high relapse rates and can not be recommended. Mature teratomas are benign germ cell tumours that can be controlled with complete surgical resection in over 90% of cases. Non-germinoma germ cell tumours are a heterogeneous group of tumours that includes very aggressive tumours such as mixed and pure choriocarcinomas, yolk sac tumours, and embryonal carcinomas; and tumours with intermediate aggressiveness such as mixed tumours with germinoma and teratoma, immature teratomas and teratomas with malignant transformation. Both radiotherapy alone and chemotherapy alone result in quite low rates of tumour control and current treatment approaches include chemotherapy and radiotherapy, with surgical removal of the tumour in some patients. Pineocytomas are benign tumours that are controlled in most cases by complete surgical resection or partial surgical resection and local field irradiation. Current treatment approaches for pineoblastomas include surgery, chemotherapy, and craniospinal irradiation with a local boost. Chemotherapy alone was used to delay irradiation in infants with very little success.

Binding sites of Helix pomatia agglutinin (HPA) were examined in 32 patients with intracranial human germ cell tumors. HPA reactivity was found in vascular endothelial cells and erythrocytes of patients with blood type A or AB. HPA-positive neoplastic cells were seen in one yolk sac carcinoma in a patient with blood group A, and in embryonal carcinomas and teratomas irrespective of blood group type. Although in 10 out of 18 germinomas neoplastic cells were totally negative for HPA, another 8 germinomas showed HPA-positive neoplastic cells which were distributed sporadically or in an area and independent of blood group types. HPA-negative germinoma patients showed a very good response to radiotherapy, whereas 4 out of 8 HPA-positive tumors showed poor radiosensitivity, with a residual lesion seen on computed tomography even after the total radiation dose of 40-50 Gy. These findings suggest that HPA-positive neoplastic cells in germinomas indicate components of differentiation of non-germinomatous germ cells. HPA-positive germinomas might be less radiosensitive than HPA-negative germinomas.

Craniospinal axis (CSA) irradiation may be associated with significant late sequelae. The recognition of the influence of dose per fraction on late sequelae and the radiosensitivity of germ cell tumours (GCT) led to the adoption of a partial transmission block (PTB) technique for patients with intracranial GCTs. The PTB allows a dose differential between the whole cranium (prophylactic area) and the primary site (high-dose area) throughout the CSA prescription. The PTB technique has been used in four patients, two with germinoma and two with non-germinomatous germ cell tumours (NGGCT). All patients received two courses of primary chemotherapy with at least a partial response prior to CSA irradiation with the PTB and a three-field boost to the primary site. There was no prolongation in the overall treatment time. The use of this 'CNS friendly' radiotherapy technique was straightforward and the potential benefit in reducing late sequelae is discussed using two isoeffect methods.

The results of treatment with platinum based combination chemotherapy in ten patients with intracranial germ cell tumours (GCT) are presented. Two patients, treated for relapse within the central nervous system (CNS), attained partial responses of short duration. One patient with systemic relapse was successfully salvaged with chemotherapy. Seven patients received primary chemotherapy, six of whom received a 'CNS friendly' regimen consisting of vincristine, etoposide, carboplatin (VEJ) prior to craniospinal axis (CSA) irradiation. Three complete and three partial responses, and one patient with stable disease, were seen prior to irradiation. All seven patients are alive and remain disease-free at a median time of 12 months after treatment. Current treatment policy for germinomas attaining complete response to two courses of VEJ is a lowered CSA dose prescription, while non-germinomatous germ cell tumours (NGGCT) receive standard total dose CSA irradiation.

This article presents a review of the spectrum of extragonadal germ cell tumors, a fascinating group of rare and biologically diverse tumors. Although like testicular germ cell tumors, these tumors are chemotherapeutically responsive, the overall prognosis is not as good. Pediatric germ cell tumors share many of the biologic characteristics of the adult tumors but are more likely to be benign. An unusual aspect of mediastinal germ cell tumors, in particular, is their association with nontreatment-related hematologic malignancies.

Non-seminomatous pineal region germ cell tumours have a poor prognosis when treated with radiation alone but little is known of the results of treatment with modern chemotherapy. Between 1983 and 1990 five pineal region germ cell tumours presented to the Charing Cross Hospital, London. All five patients received the EpPlt/OMB chemotherapy schedule with escalated dose systemic methotrexate and intra-CSF methotrexate. Two patients had had prior radiotherapy. Four patients (80%) remain well and disease-free 6 months--5 years after completing therapy. Chemotherapy is an effective modality for the treatment of pineal germ cell tumours and should be used when non-seminomatous elements are present or when the placement of ventriculo-peritoneal shunt in the presence of malignant cells in the CSF presents a risk of dissemination.

Radiation therapy (XRT) was used in the treatment of 25 patients with tumors of the pineal and suprasellar locations. A tissue diagnosis was obtained before XRT in 5 patients, and 20 were irradiated without histologic verification. The overall survival rate is 80% (76% with no evidence of disease [NED]). Megavoltage XRT was delivered to the entire neuraxis in 22 patients, and 86% (19/22) are alive from 4 to 88 months (median, 30 months) after treatment. In two of three patients treated only to local fields, tumor recurred in the spine; both are dead of disease. Biopsy-proven germinomas and multiple midline tumors responded favorably to XRT, whereas solitary pineal tumors and teratomas with marker positivity (human chorionic gonadotropin, alpha-fetoprotein) did not respond as well. The endocrinologic presentation, tumor marker status, and early response to radiation measured on computed tomography are useful means for selecting patients for radiation therapy.

A neoadjuvant (preradiotherapy) chemotherapy regimen consisting of either cyclophosphamide alone (60 to 80 mg/kg) or a modified multidrug regimen (vinblastine, bleomycin, cyclophosphamide, and cisplatin) was administered to 15 newly diagnosed patients with histologically confirmed, fully staged, primary germ-cell tumors (GCT's) of the central nervous system (CNS). There were 11 patients with germinomas and four with non-germinoma malignant GCT's. There were six females and nine males, whose median age was 13 years (range 4 months to 24 years). Seven germinoma patients (64%) had disseminated disease. For the germinoma patients, the subsequent radiotherapy dose was modified based on the response to the neoadjuvant chemotherapy, and craniospinal radiotherapy was given only to those with disseminated CNS disease at diagnosis. Ten of the 11 germinoma patients had complete disappearance of all evaluable disease after two courses of chemotherapy (cyclophosphamide in eight and multidrug in three) and one had a partial response. The planned dose of radiotherapy to the primary tumor was reduced from 5500 to 3000 rads, and the craniospinal dose was lowered from 3600 to 2000 rads. Ten patients remain in continuous disease-free remission 20+ to 89+ months after diagnosis (median follow-up period 47 months). All four patients with non-germinoma GCT's received the multidrug regimen, and two fo three patients with evaluable disease had a partial response. High-dose regional and craniospinal radiotherapy was administered thereafter, but only two patients remain in their first remission. Previously untreated germinoma is a highly chemosensitive disease and the neoadjuvant treatment strategy permits the identification of active chemotherapy regimens in newly diagnosed patients. Patients who have complete responses to neoadjuvant chemotherapy tolerate a significant radiotherapy dose reduction without compromising long-term survival, thereby allowing a reduction of some of the late effects of therapeutic radiation. Germinomas tend to disseminate early in the course of the disease and a pre-therapy staging evaluation permits individualized radiotherapy treatment planning.