Vinblastine monotherapy induction prior to radiotherapy for patients with intracranial germinoma during the COVID-19 pandemic.

BACKGROUND: Patients with localized intracranial germinoma have excellent survival. Reducing treatment burden and long-term sequelae is a priority. Intensive inpatient chemotherapy (e.g., carboPEI = carboplatin/etoposide/ifosfamide) has been effectively employed to reduce radiotherapy treatment volume/dose. Outpatient-based carboplatin monotherapy is associated with excellent outcomes in metastatic testicular seminoma (an identical pathology), and successful vinblastine monotherapy induction (with 77% tumor volume reduction after just two weekly vinblastine doses) has recently been reported in an intracranial germinoma patient. METHODS: Adapted UK guidelines for germ cell tumor management were distributed during the COVID-19 pandemic, including nonstandard treatment options to reduce hospital visits and/or admissions. This included vinblastine monotherapy for intracranial germinoma (6 mg/m2 intravenously, or 4 mg/m2 for moderate count suppression, delivered weekly). We describe two such patients treated using this approach. RESULTS: A 30-year-old male with a localized pineal tumor received 12-week vinblastine induction, with >60% volume reduction, prior to definitive radiotherapy. A 12-year-old female with a metastatic suprasellar tumor and progression at all sites of disease whilst awaiting proton radiotherapy received two vinblastine doses with good early response, including 36% primary tumor volume reduction. The patients tolerated vinblastine well. CONCLUSION: Patients with intracranial germinoma have excellent outcomes, and reduction of late effects remains a priority. The description of vinblastine monotherapy in these intracranial germinoma patients warrants further exploration.

Diagnostic radiation-induced regression of a metastatic primary intracranial germinoma: a case report.

Pineal region germinomas are sensitive to radiotherapy. Standard neurosurgical management involves obtaining a tissue biopsy and to relieve the often accompanying obstructive hydrocephalus. We present a patient with a suspected hyper-radiosensitive metastatic primary intracranial germinoma where computed tomography scanning resulted in tumor regression before radiotherapy could be administered.

Multi-institutional analysis of treatment modalities in basal ganglia and thalamic germinoma.

BACKGROUND: Central nervous system (CNS) germinomas are treatment-sensitive tumors with excellent survival outcomes. Current treatment strategies combine chemotherapy with radiotherapy (RT) in order to reduce the field and dose of RT. Germinomas originating in the basal ganglia/thalamus (BGTGs) have proven challenging to treat given their rarity and poorly defined imaging characteristics. Craniospinal (CSI), whole brain (WBI), whole ventricle (WVI), and focal RT have all been utilized; however, the best treatment strategy remains unclear. METHODS: Retrospective multi-institutional analysis has been conducted across 18 institutions in four countries. RESULTS: For 43 cases of nonmetastatic BGTGs, the 5- and 10-year event-free survivals (EFS) were 85.8% and 81.0%, respectively, while the 5- and 10-year overall survivals (OS) were 100% and 95.5%, respectively (one patient fatality from unrelated cause). Median RT doses were as follows: CSI: 2250 cGy/cGy(RBE) (1980-2400); WBI: 2340 cGy/cGy(RBE) (1800-3000); WVI: 2340 cGy/cGy(RBE) (1800-2550); focal: 3600 cGy (3060-5400). Thirty-eight patients (90.5%) received chemotherapy. There was no statistically significant difference in the EFS based on initial field extent (p = .84). Nevertheless, no relapses were reported in patients who received CSI or WBI. Chemotherapy alone had significantly inferior EFS compared to combined therapy (p = .0092), but patients were salvageable with RT. CONCLUSION: Patients with BGTGs have excellent outcomes and RT proved to be an integral component of the treatment plan. This group of patients should be included in future prospective clinical trials and the best RT field should be investigated further.

A single-center study of treatment outcomes of pediatric basal ganglia germinoma in Taiwan.

PURPOSE: A basal ganglia (BG) germinoma is a rare tumor, and the optimal treatment remains unknown. We evaluated the clinical outcomes of treatment of BG germinoma in pediatric patients in Taiwan. METHODS: We retrospectively reviewed the medical records of 34 children with BG germinoma who were treated with radiotherapy (RT) at Taipei Veterans General Hospital between 1989 and 2016. The median follow-up time is 8.3 years (1.8-25.2 years). Survival was analyzed using the Kaplan-Meier estimate. Univariate Cox proportional-hazards models were used to identify the potential risk factors. RESULTS: Only four patients (11.8%) experienced recurrence and all successfully underwent salvage therapy. One patient (2.97%) died due to suspected radiotherapy (RT)-related sarcoma in the scalp. The 2-, 3-, and 5-year DFS rates were 91.2%, 88.2%, and 79.4%, respectively; the 2-, 3-, and 5-year OS rates were 97.1%, 94.1%, and 82.4%, respectively. Focal RT showed low DFS in the Kaplan-Meier survival curves (P = .028) compared with non-focal RT (whole ventricle, whole brain, or cranial spinal area). In the univariate Cox proportional-hazards model, there was a significant difference in DFS between focal and non-focal RT (P = .03). There is no difference in DFS and OS between BG germinoma patients and non-BG germinoma patients. CONCLUSIONS: We found an excellent DFS and OS in pediatric patients with BG germinoma treated with RT. Whole ventricle irradiation is recommended for good tumor control and low treatment-related toxicity. BG germinoma patients showed similar treatment results as germinoma patients in other common sites.

Autopsy report of a late delayed radiation injury after a period of 45 years.

For delayed radiation injury, image analysis has considerably advanced, but neuropathological findings are still required to establish diagnosis. A patient who had received radiation therapy for pineal germinoma at age 14 developed neurological and psychiatric abnormalities after 15 years as a late delayed radiation injury. Autopsy at age 59 revealed diffuse changes in the white matter consisting in order of severity of myelin pallor, demyelination, and necrosis which were characterized by a lack of glial reaction. The cerebral cortex was relatively well preserved. As delayed radiation injuries, hyalinous changes in the vascular wall, angiomatous lesions and, fresh and old petechial hemorrhages were found. Moreover, vascular changes associated with arteriosclerosis were also present. Furthermore, a focal glial nodule was detected which was considered to be a new radiation-induced neoplasia. These findings suggest that late delayed radiation injury may slowly develop over 30 years and may involve damage to neuroglial stem cell compensation. It is also evident that arteriosclerotic changes and newly induced neoplasia may develop in delayed radiation injury cases.

Laparoscopic Sleeve Gastrectomy on Severe Obesity after Intracranial Germinoma Treatment: A Case Report.

Hypothalamic obesity is a clinical syndrome characterized by severe and refractory obesity that is caused by hypothalamic function impairment. Recently, bariatric surgery has been attempted for patients with hypothalamic obesity after craniopharyngioma, but experiences have not yet been accumulated in other hypothalamic disorders. Here, we report the case of a 39-year-old male patient with panhypopituitarism who received laparoscopic sleeve gastrectomy (LSG) after intracranial germinoma treatment. The patient was diagnosed with intracranial germinoma at age 15 and achieved complete remission after radiotherapy (total 50 Gy). He was obese during diagnosis [body mass index (BMI), 29.2 kg/m2], and his obesity gradually worsened after the intracranial germinoma treatment, and LSG was considered when his BMI was 48.6 kg/m2. After 1 month of hospitalized diet-exercise program, LSG was performed. After LSG, his BMI gradually decreased and reached 38.8 kg/m2 on the day of discharge (6 weeks after the surgery). Five months after LSG, his insulin resistance improved, but insulin hypersecretion remained. Fifteen months after the surgery, his BMI was 31.2 kg/m2, with marked decrease in visceral and subcutaneous fat areas (from 393.8 cm2 and 168.2 cm2 before the surgery to 111.5 cm2 and 56.3 cm2, respectively.). To our knowledge, this is the first case of LSG for hypothalamic obesity after intracranial germinoma treatment. Although the pathophysiology of hypothalamic obesity is different from that of primary obesity, LSG could be a successful therapeutic choice for patients with hypothalamic obesity after the intracranial germinoma treatment.

Secondary glioblastoma after treatment of intracranial germinoma - would radiation-only therapy still be safe? Case report.

BACK GROUND: Intracranial germinomas are one of the most radiosensitive tumors and are curable by radiotherapy (RT) alone. RT-only therapy without chemotherapy is effective. But, as patients with germinoma can expect long-term survival, the adverse effects of RT and late sequelae in survivors are of most concern. So, recently, standard treatment protocol of combination with chemotherapy and reduced dose of RT could be widely acceptable. CASE PRESENTATION: We report a patient with germinoma who developed RT-induced glioblastoma. He was diagnosed as biopsy-proven germinoma at the age of 12. Postoperatively, he underwent RT alone without chemotherapy and remained free of tumor without recurrence during long-term follow up. However, after almost 20 year, he developed RT-induced glioblastoma. CONCLUSIONS: Although RT has the highest priority among treatments on intracranial germinomas, RT-only therapy with full dose for germinoma can have delayed severe complications. So, chemotherapy prior to reduced dose RT is more desirable.

Practice patterns and survival outcomes of intracranial germinoma: an analysis of the National Cancer Database.

The goal of the study is to examine the practice pattern and survival outcome of adult and pediatric patients with intracranial germinoma. Patients from the National Cancer Database (NCDB) brain tumor registry between the years 2004-2014 with intracranial germinoma were extracted for analysis. Patients who had distant metastasis, received no treatments, or only surgery/chemotherapy alone were excluded. An age cutoff of > 21 years old was used to define the pediatric population. Patients were stratified by the treatments radiation therapy alone (RT) and chemotherapy followed by radiation therapy (C + RT). 445 patients with intracranial germinoma meeting our inclusion criteria were identified. Of the adult patients, 65.7% received RT and 34.3% received C + RT, compared to the pediatric patients, where 31.8% received RT and 68.2% received C + RT. Those patients who received C + RT had a lower radiation dose compared to the RT group (p < 0.001). The 5 and 10 year overall survival (OS) for the entire cohort was 92.6 and 87.9%, respectively. Univariate analysis demonstrated improved OS with younger age, private insurance, C + RT treatment, and pediatric patients. Only age and insurance type remained significant on multivariate analysis. The 5 year OS was 92.6% (RT) versus 97.2% (C + RT) (p = 0.307) and 83.4% (RT) versus 95.4% (C + RT) (p = 0.122) in the pediatric and adult patients, respectively. There is a higher use of C + RT with an accompanied reduction in RT dose in the treatment of intracranial germinoma. There is no difference in survival between the treatment approaches of RT or C + RT in the NCDB patient cohort.

Efficacy of Ifosfamide-Cisplatin-Etoposide (ICE) Chemotherapy for a CNS Germinoma in a Child With Down Syndrome.

Intracranial germ cell tumor is sometimes associated with Down syndrome; however, no optimal treatment has been developed due to the high risk of recurrence and treatment-related mortality. Here, we report on a patient with an intracranial germinoma in the bilateral basal ganglia. The patient received 3 courses of ifosfamide-cisplatin-etoposide in combination with whole-brain irradiation (24 Gy), with no serious complications. The patient is alive and disease free 16 months after the initial diagnosis. This regimen is a feasible treatment for intracranial germ cell tumor associated with Down syndrome, although careful attention must be paid to the increased risk for severe infection.

Successful live birth in a patient who underwent cranial radiotherapy and systemic chemotherapy by implantation of a cryopreserved blastocyst on day 7.

Preservation of fertility has been recommended for cancer-bearing patients of reproductive age before undergoing cancer treatment. However, there are many considerations and it is difficult to preserve fertility for all patients undergoing therapy for malignancies. Female cancer survivors had lower pregnancy and live birth rates compared with others that underwent assisted reproductive technologies (ARTs). We should continue to consider the issue of infertility in patients who underwent therapies for malignancies. This is the first report of a successful live birth in a patient with a cranial tumor who underwent radiotherapy and chemotherapy after implantation of an autologous embryo. The patient was a 27-year-old Japanese woman. She was diagnosed with suprasellar germinoma at 13 years of age, and she developed panhypopituitarism after radiotherapy and chemotherapy. At 27 years of age, she began infertility treatment with in-vitro fertilization (IVF). The level of anti-Mallerian hormone (AMH) was 4.29 ng/ml. After ovarian stimulation by high purified human menopausal gonadotropin (HP-hMG), she obtained two blastocysts and became pregnant by implantation of a cryopre- served blastocyst. At 37 gestational weeks, she delivered a healthy female baby by cesarean section.

The necessity of long-term follow-up including spinal examination after successful initial treatment of intracranial germinoma: case reports.

INTRODUCTION: Intracranial germinomas seldom recur at spinal space following whole-brain or whole-ventricular (WV) radiotherapy. The majority of the spinal recurrence takes place within 5 years after treatment; therefore, late spinal failure beyond 5 years after successful initial treatment is rare. CASE PRESENTATIONS: We describe the cases of two patients with intracranial germinoma, who developed spinal recurrence 7 and 9 years after the initial treatment with WV radiotherapy combined with and without chemotherapy, respectively. In both cases, spinal recurrent tumors were histologically diagnosed as germinoma and they were successfully treated with chemotherapy and local radiotherapy without tumor recurrence for 11 years and 11 months, respectively. CONCLUSION: Intracranial germinomas may potentially present with spinal recurrence many years after successful initial WV radiotherapy. Physicians must be aware of patients' symptoms during the clinical examination. Regular long-term monitoring, including spinal examination, is necessary for 5-10 years or longer.

Diabetes insipidus in pediatric germinomas of the suprasellar region: characteristic features and significance of the pituitary bright spot.

The pituitary bright spot is acknowledged to indicate functional integrity of the posterior pituitary gland, whilst its absence supports a diagnosis of central diabetes insipidus (DI). This feature was evaluated, together with the incidence and clinical characteristics of DI in children with suprasellar/neurohypophyseal germinomas. We performed a review of all suprasellar (SS) or bifocal (BF) germinoma pediatric patients treated in Toronto since 2000. Demographics, symptomatology, treatment outcome and imaging were evaluated. Nineteen patients fulfilled inclusion criteria (10 SS, 9 BF; median age 12.5 years (6.2-16.8 years)). All remained alive at 6.4 years median follow-up (1.2-13.7 years) after receiving chemotherapy and radiotherapy (13 focal/ventricular, four whole brain, two neuraxis), with only one progression. All had symptoms of DI at presentation with a symptom interval above one year in eight cases (42 %). Desmopressin was commenced and maintained in 16 patients (84 %). The pituitary bright spot was lost in most diagnostic interpretable cases, but was appreciated in three patients (18 %) who had normal serum sodium values compared to 'absent' cases (p = 0.013). For two such cases, spots remained visible until last follow-up (range 0.4-3.3 years), with one still receiving desmopressin. No case of bright spot recovery was observed following therapy. Protracted symptom intervals for germinoma-induced central DI may reflect poor clinical awareness. Explanations for persistence of the pituitary bright spot in symptomatic patients remain elusive. Desmopressin seldom reverses the clinical features of germinoma-induced DI to allow discontinuation, nor does treatment cause bright spot recovery.

Pure germinomas of the central nervous system: treatment strategies and outcomes.

To evaluate the role of chemotherapy and radiation therapy in the treatment of pure germinomas of the central nervous system (CNS). We reviewed a historical cohort of 79 patients between the ages of 3-35 years who received definitive treatment for newly diagnosed, pure CNS germinoma between 1985 and 2010 at the University of California, San Francisco (UCSF). Median age at diagnosis was 15 years (interquartile range, IQR 12-20 years) and 61 (77.2 %) patients were male. Median follow-up for the cohort was 111.1 months (IQR 45.7-185.1 months). Five-year PFS rate was 86.4 % (95 % CI 76.1-92.4) and 5 year OS rate was 93.0 % (95 % CI 84.1-97.1). Median PFS was 104.6 months (IQR 41.4-170.1 months). Fourteen patients progressed and 8 died of their disease. Patients who received focal irradiation (XRT) and chemotherapy had a significantly higher rate of progression compared to those who received whole brain irradiation (WBI) or whole ventricle irradiation (WVI). Three of 8 patients had a PR to chemotherapy and received focal XRT progressed whereas only 1 of 9 patients who had a CR to chemotherapy who went on to receive focal XRT progressed. Elevation of hCGß > 50 mIU/ml was not significantly associated with disease progression (HR 5.64, 95 % CI 0.97-32.7, p = 0.054). Patients treated with WBI or WVI with or without chemotherapy achieve better disease control compared to patients treated with focal XRT + chemotherapy.

[Endoscopic approach to ventricular atrium for biopsy of pineal region tumour: case report]. / Abordaje endoscópico al atrio ventricular para toma de biopsia de tumor de la región pineal: a propósito de un caso.

INTRODUCTION: The usual endoscopic approach in the management of pineal region tumours consists of inserting the scope into the frontal horn of the lateral ventricle and advancing it through the foramen of Monro into the third ventricle. We report the case of a patient with a pineal tumour on whom we used an endoscopic approach through the ventricular atrium to obtain a biopsy by opening the choroidal fissure. CLINICAL CASE: This young 25-year-old man presented with headache and double vision. Papilloedema and Parinaud's syndrome were found on physical examination. Cranial magnetic resonance revealed a pineal mass and hydrocephalus. We initially performed a third ventriculostomy and a tumour biopsy through a frontal burr hole. The tissue sample was not useful for pathological diagnosis and we decided to perform a second endoscopic biopsy. CONCLUSIONS: The endoscopic approach to pineal region masses, reaching the ventricular atrium through a parietal burr hole and opening the choroidal fissure, makes it possible to take a biopsy using a single endoscopic approach without needing to cross other ventricular structures.

Treatment strategy for intracranial primary pure germinoma.

OBJECT: This prospective randomized clinical study will address the efficacy of radiation (RT)-alone and combined with pre-RT chemotherapy (CTX) treatments and propose the novel standard treatment strategy for intracranial primary pure germinoma. MATERIALS AND METHODS: Between 2005 and 2008, there were 54 patients diagnosed with intracranial primary pure germinomas in a single institute. Twenty-eight patients were enrolled. The mean age of the patients was 16.2 years (range 6-31 years). There were 19 men and 9 women (men/women ratio = 2.1:1). There were 21 patients with solitary tumors and 7 with multiple tumors. These patients were randomized as RT-only treatment group (11 solitary and 3 multiple tumors) and combined (10 solitary and 4 multiple tumors, neo-adjuvant CTX followed by response-adapted RT) treatment group. The follow-up period for RT only group has a median of 58 months (mean 58.2 months, range 41-82 months), and for combine therapy group, the median was 68.5 months (mean 67.8 months, range 41-88 months). All 14 patients in the RT-only group showed complete response (CR) and no recurrence. Eleven patients in the combined group had CR and three patients had partial response after neo-adjuvant CTX. All patients responded to RT as CR without recurrence. At the time of analysis, all 28 patients were alive without evidence of disease. CONCLUSION: Neo-adjuvant CTX for localized germinomas seems to be unnecessary as a method to reduce radiation dose in our RT protocol. However, the effective control of multifocal or disseminated germinoma can be achieved by neo-adjuvant CTX followed by response-adapted reduced dose RT.

Reversible hypothalamic dysfunction in optic nerve germinoma.

Primary optic apparatus germ cell tumors are rare. There have been only 6 cases reported in the literature. Although they often disturb the hypothalamus-pituitary-adrenal axis and cause progressive visual loss, the influence of treatment outcomes on hypothalamic autoregulation has never been mentioned. Here, we report a patient with an optic nerve germinoma who presented with reversible visual and hypothalamic dysfunction, and we discuss the possible mechanisms and pathogenesis.

[Clinical analysis of 45 patients with intracranial germinoma treated by radiotherapy].

OBJECTIVE: To report the prospective efficacy of 45 patients intracranial germinoma treated by radiotherapy and discuss its treatment. METHODS: From February 1998 to October 2007, a total of 45 intracranial germinoma patients were performed radiotherapy, including 15 combined chemotherapy in the Department of Oncology. Of them 23 were pathologically diagnosed while 22 cases were clinical diagnosed. Life table method showed the 5-year and 10-year survival rate. RESULTS: Forty patients were followed-up. Most symptoms of the patients were significantly reduced or disappeared completely. The 5-year and 10-year survival rate of all patients were 84% and 74%. CONCLUSION: Radiotherapy is the main treatment for intracranial germinoma. Craniospinal irradiation, whole brain irradiation and partial brain irradiation are the main treatments. Radiotherapy combined with chemotherapy, which can reduce the radiation range and dose will be the trend.

Salvage craniospinal irradiation for recurrent intracranial germinoma: a single institution analysis.

This study investigated the effectiveness and safety of low-dose salvage craniospinal irradiation (CSI) for recurrent germinoma. We retrospectively reviewed long-term tumor control and late adverse effects in 15 recurrent germinoma patients treated at our hospital between 1983 and 2019. Following the first recurrence of germinoma, seven were treated with 24-30 Gy of salvage CSI, three underwent non-CSI, and five were treated with only chemotherapy. CSI achieved a significantly better recurrence-free survival rate after the first recurrence compared to other strategies (100% vs 33%, p < 0.001: log-rank test). To evaluate the safety of salvage CSI, we assessed the outcomes at the final follow-up of seven patients who received salvage CSI at first recurrence and three patients who received salvage CSI at second recurrence. The median follow-up period was 220 months after initial treatment. Five patients who received 40-50 Gy of radiation therapy or underwent multiple radiation therapy before salvage CSI were classified into Group A, whereas five patients treated with platinum-based chemotherapy and 24-32 Gy of radiation therapy to the primary site, whole ventricle, or whole brain were classified into Group B. In Group A, one had endocrine dysfunction and the other had visual dysfunction. None were socially independent. Meanwhile, in Group B, no endocrine or visual dysfunction was found, and three patients were socially independent. Salvage CSI achieved excellent tumor control in recurrent germinoma and was safe in patients initially treated with low-dose radiation therapy and chemotherapy.

Bifocal lesions have a poorer treatment outcome than a single lesion in adult patients with intracranial germinoma.

Intracranial germinoma (IG) rarely occurs in adults. Its optimal treatment strategy is unclear. We evaluated the outcomes of radiotherapy in adults with intracranial germinoma. Data of 29 adult patients (age, 18-52 years; median age, 24.3 years) with IG treated with radiotherapy at Taipei Veterans General Hospital were retrospectively reviewed. They were followed up for a median time of 5.9 years (range, 1.0-12.8 years). We used the Kaplan-Meier method to estimate the progression-free survival (PFS) and overall survival (OS), and univariate and multivariate Cox proportional hazards regression models to identify the factors affecting PFS. PFS and OS were compared between adult and pediatric patients with IG. The 1-, 3-, and 5-year PFS rates were 96.6%, 85.8%, and 77.8%, respectively, in the adult patients, and the OS rate were all 100%. Seven patients (24.1%) experienced recurrence, and in six of them, salvage therapy successfully controlled the disease. Two patients (6.9%) died after 5 years of follow-up due to disease progression and central pontine myelinolysis. In the univariate and multivariate Cox analysis, bifocal lesions had a significantly lower PFS than those with single lesions (p = 0.008). Kaplan-Meier survival analysis showed that adult patients had a poorer PFS (p = 0.06) and OS (p = 0.025) than pediatric patients. Our study showed bifocal lesions were associated with lower PFS than a single lesion among adult IG patients, and adult IG patients tended to have poorer PFS and OS compared to pediatric IG patients. For adult patients with bifocal IG, we recommend treatment with craniospinal irradiation, whole ventricle irradiation (WVI) with chemotherapy, or frequent spine images follow-up for patients who received only WVI.

Phase II trial of response-based radiation therapy for patients with localized germinoma: a Children's Oncology Group study.

BACKGROUND: The study aimed to evaluate whether simplified chemotherapy followed by dose-reduced irradiation was effective for treating patients (ages 3-21 years) with localized germinoma. The primary endpoint was 3-year progression-free survival (PFS) rate. METHODS: Patients with a complete response to chemotherapy with carboplatin and etoposide received 18 Gy WVI + 12 Gy boost to the tumor bed. Patients with partial response proceeded to 24 Gy WVI + 12 Gy. Longitudinal cognitive functioning was evaluated prospectively on ALTE07C1 and was a primary study aim. RESULTS: One hundred and fifty-one patients were enrolled; 137 were eligible. Among 90 evaluable patients, 74 were treated with 18 Gy and 16 with 24 Gy WVI. The study failed to demonstrate noninferiority of the 18 Gy WVI regimen compared to the design threshold of 95% 3-year PFS rate, where, per design, patients who could not be assessed for progression at 3 years were counted as failures. The Kaplan-Meier (KM)-based 3-year PFS estimates were 94.5 ± 2.7% and 93.75 ± 6.1% for the 18 Gy and 24 Gy WVI cohorts, respectively. Collectively, estimated mean IQ and attention/concentration were within normal range. A lower mean attention score was observed at 9 months for patients treated with 24 Gy. Acute effects in processing speed were observed in the 18 Gy cohort at 9 months which improved at 30-month assessment. CONCLUSIONS: While a failure according to the prospective statistical noninferiority design, this study demonstrated high rates of chemotherapy responses, favorable KM-based PFS and OS estimates in the context of reduced irradiation doses and holds promise for lower long-term morbidities for patients with germinoma.