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.

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.

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.

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.

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.

Relapse pattern and quality of life in patients with localized basal ganglia germinoma receiving focal radiotherapy, whole-brain radiotherapy, or craniospinal irradiation.

BACKGROUND AND PURPOSE: The optimal target volume in localized basal ganglia (BG) germinoma is still undetermined. Thus, based on the relapse pattern and health-related quality of life (HRQOL), we evaluated three target volumes. MATERIAL AND METHODS: The clinical data of 161 patients with localized BG germinoma were included in this retrospective study. Relapse status and relapse sites after treatment were explored. HRQOL was evaluated using the Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0) (≤15 years) and Short Form-36 (SF-36) (>15 years) questionnaires based on the patients' age at last follow-up. RESULTS: After a median follow-up duration of 83 months (range, 20-214 months), 19 patients experienced relapse, including 15, 4, and 0 patients in the focal radiotherapy (FR) (n = 35), whole-brain radiotherapy (WBRT) plus boost (n = 109), and craniospinal irradiation (CSI) plus boost (n = 17) groups, respectively. The 5-year disease-free survival rates were 74.3%, 97.2%, and 100%, respectively (p < 0.001). Among the 15 patients who relapsed after FR, 14 had positive radiological findings, including seven (50.0%) with lesions in the periventricular area and seven (50.0%) with frontal lobe lesions. Relapse in both these areas were significantly reduced by WBRT or CSI. HRQOL data were available for 69 patients, who generally scored low. Among 38 patients evaluated by SF-36, those receiving CSI had significantly lower mental component scores than those receiving WBRT (p = 0.027) or FR (p = 0.011). CONCLUSIONS: Considering both disease control and HRQOL, WBRT is the optimal target volume in our series. The relapse pattern identified in patients receiving FR is informative for further treatment volume optimization.

Long-Term Outcomes and Sequelae Analysis of Intracranial Germinoma: Need to Reduce the Extended-Field Radiotherapy Volume and Dose to Minimize Late Sequelae.

PURPOSE: We aimed to refine the radiotherapy (RT) volume and dose for intracranial germinoma considering recurrences and long-term toxicities. MATERIALS AND METHODS: Total 189 patients with intracranial germinoma were treated with RT alone (n=50) and RT with upfront chemotherapy (CRT) (n=139). All cases were confirmed histologically. RT fields comprised the extended-field and involved-field only for primary site. The extended-field, including craniospinal, whole brain (WB), and whole ventricle (WV) for cranial field, is followed by involved-field boost. The median follow-up duration was 115 months. RESULTS: The relapses developed in 13 patients (6.9%). For the extended-field, cranial RT dose down to 18 Gy exhibited no cranial recurrence in 34 patients. In CRT, 74 patients (56.5%) showed complete response to chemotherapy and no involved-field recurrence with low-dose RT of 30 Gy. WV RT with chemotherapy for the basal ganglia or thalamus germinoma showed no recurrence. Secondary malignancy developed in 10 patients (5.3%) with a latency of 20 years (range, 4 to 26 years) and caused mortalities in six. WB or craniospinal field rather than WV or involved-field significantly increased the rate of hormone deficiencies, and secondary malignancy. RT dose for extended-field correlated significantly with the rate of hormone deficiencies, secondary malignancy, and neurocognitive dysfunction. CONCLUSION: De-intensifying extended-field rather than involved-field or total scheme of RT will be critical to decrease the late toxicities. Upfront chemotherapy could be beneficial for the patients with complete response to minimize the RT dose down to 30 Gy. Prospective trials focused on de-intensification of the extended-field RT are warranted.

Intracranial Germinoma Misdiagnosed as Hyperthyroidism: A Case Report and Review of the Literature.

Intracranial germ cell tumors (GCTs) are relatively rare, which account for 0.5% of all primary intracranial neoplasms. Intracranial germinomas most commonly occur in the pineal and suprasellar region, making up the majority of all intracranial GCTs. For its diversified clinical manifestations, the diagnosis is easily confused with other diseases. Here, we present a case of a 19-year-old boy with intracranial germinoma who was preliminarily misdiagnosed as hyperthyroidism for the symptoms of weight loss and thyroid dysfunction.

Induction Chemotherapy Reduces Radiation Therapy Dose and Volume in the Treatment of Intracranial Germinoma: Results of the SMC-G13 Trial.

PURPOSE: We performed a prospective single-arm trial (NCT02782754) to explore the feasibility of reducing radiation therapy (RT) dose when induction chemotherapy is combined in the treatment of intracranial germinoma with beta-human chorionic gonadotropin levels <200 mIU/mL. METHODS AND MATERIALS: All patients aged 3 to 35 years from November 2012 to June 2018 were eligible for this study. Four cycles of induction chemotherapy were given before RT. Carboplatin/etoposide and cyclophosphamide/etoposide regimens were used in alternation every 3 weeks. A dose of 18 Gy of craniospinal RT for metastatic tumors, whole brain RT for basal ganglia tumors, or otherwise whole ventricular RT followed by 12.6 Gy of boost RT to the primary tumor bed was administered after induction chemotherapy. The primary endpoint of this study was progression-free survival. RESULTS: A total of 41 consecutive patients were enrolled (location: suprasellar in 12, pineal in 12, both suprasellar and pineal in 11, and basal ganglia in 6 patients). Eleven patients had leptomeningeal seeding. Toxicity during chemotherapy was mild, except for bone marrow suppression. Tumor status after induction chemotherapy was complete response in 33 patients and partial response in 8. All but 2 patients completed the scheduled treatment. All patients but 1 remained event free during a median follow-up of 3.4 (range, 0.3-7.0) years from diagnosis. The 1 patient experienced relapse and died of tumor bleeding. Late effects were not significant except for neuroendocrine dysfunction already present at diagnosis. Vertical growth and cognitive function were not significantly disturbed by treatment. CONCLUSIONS: This study showed the feasibility of reducing RT dose/volume with induction chemotherapy in pathologically pure germinoma with elevated beta-human chorionic gonadotropin levels up to 200 mIU/mL.

Optimization of Intracranial Germinoma Treatment: Radiotherapy Alone with Reduced Volume and Dose.

PURPOSE: We investigated optimal management for intracranial germinoma, including target volume and dose of radiation therapy (RT) and the combination of RT and chemotherapy (CTx). METHODS AND MATERIALS: We retrospectively evaluated 213 patients with intracranial germinoma treated between 1971 and 2017. Treatment policies changed as diagnostic techniques and clinical experience improved. In the 1980s, trial RT and tumor marker study were performed, and craniospinal irradiation was performed to treat patients with presumed germinoma. CTx was introduced in 1991, and RT volume was reduced in patients showing a complete response. In 2012, the policy was changed to a "reduced volume/dose RT alone" approach, involving a smaller target volume (the whole ventricle/whole brain for localized disease) without CTx. RT doses were gradually reduced to 36 Gy for primary tumors and 18 Gy for neuraxis. RESULTS: The median age was 16 years. In total, 118 and 95 patients had pathologically proven and presumed germinoma, respectively, and 151 and 62 patients had localized and multifocal or metastatic diseases, respectively. With a median follow-up of 141 months, the 10-year disease-free and overall survival rates were 91.6% and 95.6%, respectively. Recurrence rates were similar for patients receiving RT-only (9 of 137, 6.6%) and those receiving CTx + RT (4 of 73, 5.5%); all patients receiving CTx-only experienced recurrences (3 of 3, 100%). Rates were the highest in the focal RT group (10 of 29, 34.5%) but were relatively low in the whole ventricle/whole brain RT (3 of 51, 5.9%) and craniospinal irradiation groups (0 of 130, 0%). Infield failure occurred in 3 patients. Fourteen patients died of recurrence (n = 4), secondary malignancy (n = 4), CTx-related toxicity (n = 2), and others (n = 4). Among the 33 patients who received "reduced volume/dose RT alone" treatment, 2 (6.1%) experienced recurrence in the spinal cord and biopsy tract, respectively. CONCLUSIONS: The additional benefit of CTx in the treatment of intracranial germinoma seems minimal. An RT-only approach with reduced target volume and dose seems reasonable.

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.

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.

Treatment outcomes based on radiation therapy fields for bifocal germinoma: Synchronous or disseminated disease?

Intracranial germinoma sometimes present as bifocal germinoma, and whether bifocal germinoma should be treated as a synchronous or disseminated disease remains unclear. This study aimed to determine the optimal treatment modality for bifocal germinoma. Patients with bifocal germinoma who received radiotherapy (RT) from March 1990 to August 2017 were included for analysis. A total of 21 patients were included. The median follow-up period was 76.2 months (range, 6.2-305.4 months). There were 17 patients who received cranio-spinal irradiation (CSI) with local RT; 3, whole ventricular RT (WVRT) with local RT; and 1, local RT only. Three recurrences occurred (1 patient each among those who underwent CSI, WVRT, and local RT). Recurrence in the patient who received CSI and who received WVRT occurred in the right thalamus and right frontal convexity, respectively. Meanwhile, the patient who received local RT showed not only a recurred lesion in the hypothalamus, but also cerebrospinal fluid seeding. For this patient, salvage CSI was performed and complete response was achieved after treatment. However, after 9 years and 6 months, he was diagnosed with glioblastoma and expired. As for toxicity, although 17 patients showed decrease in complete blood count levels during treatment, all patients recovered soon after treatment completion. Our findings suggest that bifocal germinoma may be considered as a disseminated disease when considering the patterns of failure according to RT fields. In addition, patients who received CSI showed low acute toxicity rates. However, further studies are necessary to confirm these findings.

Spontaneous Regression in Intracranial Germinoma: Case Report and Literature Review.

BACKGROUND: Spontaneous regression in intracranial germ cell tumors (GCTs) is an extremely rare phenomenon with only 9 cases reported. The mechanism and natural history of this phenomenon are still equivocal. METHODS: A 12-year-old boy presented with a lesion in the suprasellar region with involvement of basal ganglia and corpus callosum. After 1 month, his symptoms were relieved, and magnetic resonance imaging demonstrated a remarkable regression of the lesion. Three months later, the boy's symptoms deteriorated, and magnetic resonance imaging revealed regrowth and enlargement of the lesion. Diagnosis of germinoma was confirmed via biopsy, and radiation therapy achieved complete response. We performed a systematic literature review of spontaneous regression of intracranial GCTs. The natural history of these cases was analyzed, and hypotheses in the studies were discussed. RESULTS: Spontaneous regression is extremely rare with only 10 cases reported, including the present case. There were 9 male patients and 1 female patient with mean age 22.1 ± 10.3 years (range, 12-43 years). Nine cases were diagnosed as germinoma, and 4 cases included an episode of regression followed by regrowth. The mechanism of tumor regression in intracranial GCTs remains unclear. Four hypotheses were proposed, including radiation exposure, surgical procedures, effects of steroids, and immune reaction triggered by intervention. CONCLUSIONS: Tumor regression in intracranial GCTs could be a iatrogenic transient phenomenon, caused by complex immune reactions triggered by interventions.

Upfront chemotherapy followed by response adaptive radiotherapy for intracranial germinoma: Prospective multicenter cohort study.

PURPOSE: To assess the efficacy of upfront chemotherapy followed by response-adapted reduced-dose/reduced-volume radiotherapy (RT) for intracranial germinoma. MATERIALS AND METHODS: Ninety-one patients from five institutions were registered in the KSPNO G051/G081 Protocol. Germinomas were classified as solitary or multiple/disseminated diseases, and upfront chemotherapy was administered. For all patients with multiple or disseminated disease, and patients with partial response after chemotherapy, 19.5-24 Gy of craniospinal irradiation plus 10.8-19.8 Gy of tumor bed boost were planned. For patients with complete response (CR), reduced-dose RT (30.6 Gy) was planned, along with a reduced field for solitary lesions. RESULTS: The median patient age was 14 (range, 3-30) years. Sixty-five patients (71.4%) had a solitary lesion. The median follow-up duration was 67.9 (range, 6.6-119.3) months. Recurrence was not observed in 32 patients in the protocol compliant group. Four patients (4.4%) in the protocol non-compliant group experienced relapse after CR and one patient died of the disease. The 5-year and 7-year overall survival rates were 98.8% and 98.8%, while the corresponding event-free survival rates were 96.6% and 93.8%, respectively. All three patients with basal ganglia germinomas who were treated with local RT experienced recurrence outside the RT field. Among the 23 patients with pineal or suprasellar lesions who received whole-ventricle RT, there was no recurrence. CONCLUSIONS: Currently used upfront chemotherapy followed by reduced-dose, reduced-volume RT appears acceptable, when whole-ventricle RT for pineal or suprasellar tumors and, at minimum, whole-brain RT for basal ganglia/thalamus lesions are applied.

Redefining Ventricular Target Volume in Germinoma: Is Inclusion of Temporal Horns Necessary?

PURPOSE: We reviewed the outcomes of a retrospective germinoma cohort and analyzed radiation therapy plans to determine dosimetric differences for critical structures. METHODS AND MATERIALS: Data from pediatric patients treated with photon radiation for intracranial germinoma were analyzed for clinical outcomes and dosimetry to critical structures, with particular interest in the temporal ventricular horns (TVHs). A consensus contour was generated for TVH-sparing ventricular clinical target volumes (CTVs) via deformable image registration. RESULTS: Twelve and 10 patients had their TVHs included or excluded in their ventricular CTVs, respectively. All patients were living at the time of analysis. One patient relapsed in the fourth ventricle, which had been omitted from the radiation therapy field. Mean dose was significantly lower to the hippocampi (Δ = -578 cGy, P = .0016) and temporal lobes (Δ = -599 cGy, P = .0007) in the TVH-excluded cohort compared with those with TVHs included in the treatment field. CONCLUSIONS: Exclusion of the TVHs from the CTV results in significant dose sparing to the hippocampi and temporal lobes. Clinical outcomes remain excellent with no deaths and no TVH failures. Exclusion of TVHs from the ventricular CTV in germinoma requires prospective study.

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.