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1.
Pediatr Blood Cancer ; 70(10): e30601, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37501569

RESUMEN

BACKGROUND: The role of neoadjuvant chemotherapy in treating patients with metastatic central nervous system (CNS) germinoma is controversial. METHODS: We compared the relapse-free survival (RFS) of different treatment modalities by performing a meta-analysis using published data. We summarized all data using standard descriptive statistics. We used the Kaplan-Meier method to estimate RFS and their corresponding 95% confidence intervals (CIs). We used the log-rank test for the comparison of survival functions. RESULTS: We identified 97 patients with a median age at presentation of 15 years (range: 7-38). Sites of metastasis were cerebrospinal fluid (CSF) disease only (n = 12), brain parenchyma (n = 18), spinal cord (n = 9), ventricular and CSF (n = 10), ventricular only (n = 31), and other (n = 17). The 3-year RFS among patients who received any form of radiotherapy was 89% (95% CI: 83-96) compared with 0% for patients who received a chemotherapy-only regimen (p = .001). Five-year RFS among patients who received craniospinal irradiation (CSI) was 92% (95% CI: 84-100) compared with 76.4% (95% CI: 63-90) in the non-CSI group (with or without neoadjuvant chemotherapy) (p = .014). Five-year RFS of patients who received CSI less than 24 Gy with neoadjuvant chemotherapy was 100% compared with 92% (95% CI: 83-100) CSI dose greater than or equal to 24 Gy alone (p = .3). CONCLUSIONS: Our analysis does not support avoiding spinal irradiation among patients with radiographic metastatic CNS germinoma. Future studies are needed to confirm whether neoadjuvant chemotherapy will allow a reduction of irradiation dose without compromising survival.


Asunto(s)
Neoplasias Encefálicas , Neoplasias del Sistema Nervioso Central , Germinoma , Humanos , Niño , Adolescente , Adulto Joven , Adulto , Terapia Neoadyuvante/métodos , Neoplasias Encefálicas/patología , Recurrencia Local de Neoplasia/patología , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Germinoma/tratamiento farmacológico , Germinoma/patología , Médula Espinal/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios Retrospectivos
2.
J Neurooncol ; 162(2): 443-448, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37039951

RESUMEN

PURPOSE: To determine long-term outcomes of a cohort of children with germinoma treated with chemotherapy and radiation therapy without primary tumor boost even in the absence of complete response to chemotherapy METHODS: This retrospective study analyzed the outcome of patients with germinoma consecutively diagnosed and treated at a tertiary care center from January 2000 to December 2021. MRIs were reviewed by two radiologists, blinded to patient data. Tumor location at diagnosis, tumor response to chemotherapy and at completion of radiation therapy and site of relapse were assessed. Tumor response was assessed radiologically by determining the tumor size and response on diffusion-weighted imaging, in addition to biochemical, cytological parameters and neurological status. RESULTS: Of 46 pediatric germinoma patients, 29 children (14 male; median age 12.8 years) received no primary tumor boost. Median follow-up was 63 months (range 9-187 months). Twenty-five children had localized disease and tumor location was suprasellar (n = 11), pineal (n = 10), bifocal (n = 3) and basal ganglia (n = 1) while 4 children had metastatic disease at presentation. All patients completed multi-agent chemotherapy followed by either ventricular irradiation (VI) (23.4 Gy) (n = 23), whole brain (WBI) (23.4 Gy) (n = 5) or craniospinal radiation (CSI) (23.4 Gy) (n = 1). Two children, who had localized disease at presentation and received VI after chemotherapy, relapsed 9 months and 32 months after completion of treatment respectively. No patient had a local relapse. Location of relapse was distant, outside (n = 1) and out- and inside (n = 1) the irradiation field. Five-year progression free survival (PFS) was 91% and overall survival (OS) was 100%. CONCLUSIONS: In this case series, excellent 5-year PFS and OS rates were achieved with chemotherapy followed by radiation therapy of 23.4 Gy delivered without primary tumor boost. No local relapse was observed despite omitting primary tumor boost in patients with localized and metastatic germinoma.


Asunto(s)
Neoplasias Encefálicas , Germinoma , Niño , Humanos , Masculino , Estudios Retrospectivos , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Germinoma/terapia , Germinoma/tratamiento farmacológico , Encéfalo/patología , Dosificación Radioterapéutica , Estudios de Seguimiento
3.
JCO Glob Oncol ; 9: e2200257, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-37075267

RESUMEN

PURPOSE: This prospective Brazilian single-arm trial was conducted to determine response to chemotherapy and survival after response-based radiotherapy in children with intracranial germinomas, in the setting of a multi-institutional study in a middle-income country (MIC) with significant disparity of subspecialty care. PATIENTS AND METHODS: Since 2013, 58 patients with histologic and/or serum and CSF tumor marker evaluations of primary intracranial germ cell tumors were diagnosed; 43 were germinoma with HCGß levels ≤200 mIU/mL and five between 100 and 200 mIU/mL. The treatment plan consisted of four cycles of carboplatin and etoposide followed by 18 Gy whole-ventricular field irradiation (WVFI) and primary site(s) boost up to 30 Gy; 24 Gy craniospinal was prescribed for disseminated disease. RESULTS: Mean age 13.2 years (range, 4.7-25.5 years); 29 were males. Diagnosis was made by tumor markers (n = 6), surgery (n = 25), or both (n = 10). Two bifocal cases with negative tumor markers were treated as germinoma. Primary tumor location was pineal (n = 18), suprasellar (n = 14), bifocal (n = 10), and basal ganglia/thalamus (n = 1). Fourteen had ventricular/spinal spread documented by imaging studies. Second-look surgery occurred in three patients after chemotherapy. Thirty-five patients achieved complete responses after chemotherapy, and eight showed residual teratoma/scar. Toxicity was mostly grade 3/4 neutropenia/thrombocytopenia during chemotherapy. At a median follow-up of 44.5 months, overall and event-free survivals were 100%. CONCLUSION: The treatment is tolerable, and WVFI dose reduction to 18 Gy preserves efficacy; we have demonstrated the feasibility of successfully conducting a prospective multicenter trial in a large MIC despite resource disparity.


Asunto(s)
Neoplasias Encefálicas , Germinoma , Masculino , Humanos , Niño , Adolescente , Femenino , Estudios Prospectivos , Brasil , Estudios Retrospectivos , Neoplasias Encefálicas/terapia , Germinoma/tratamiento farmacológico , Germinoma/patología , Biomarcadores de Tumor
4.
J Radiat Res ; 64(2): 428-437, 2023 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-36610798

RESUMEN

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.


Asunto(s)
Neoplasias Encefálicas , Irradiación Craneoespinal , Germinoma , Humanos , Estudios Retrospectivos , Germinoma/radioterapia , Germinoma/tratamiento farmacológico , Germinoma/patología , Neoplasias Encefálicas/tratamiento farmacológico , Encéfalo/patología , Dosificación Radioterapéutica , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/patología , Estudios de Seguimiento
5.
Pituitary ; 25(6): 854-860, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35986827

RESUMEN

PURPOSE: Due to the effectiveness of growth hormone therapy (GHT), the number of cancer survivors receiving GHT has increased. Previous studies had indicated that GHT was not associated with the increasing risks of tumor recurrence and development with second neoplasm (SN) in cancer survivors. However, to date, research on those risks in germinoma survivors is still limited. The aim of this study is to evaluate the impact of GHT in relation to tumor recurrence and development with SN in pure germinoma survivors. METHODS: This retrospective cohort study was approved by the Ethical Committee for Epidemiology of our institution. Seventy-three consecutive patients who underwent a biopsy of the lesion and were diagnosed with pure germinoma were retrospectively studied. They (median age, 15.0 years) were followed up more than 1 year after biopsy (median follow-up period, 14.3 years). The following data was obtained from the medical records of the patients: age, sex, preoperative magnetic resonance imaging findings, hormonal replacement, and events including tumor recurrence and/or SN. RESULTS: In our patient series, 16 patients (21.9%) who were more likely to have neurohypophysial lesion and receive multiple hormonal therapies had received GHT. No significant differences in the rates of tumor recurrence and development with SN were observed between the patients who had and had not received GHT. Moreover, the recurrence-free survival and overall survival rates were not different between the patients who had and had not received GHT. CONCLUSIONS: GHT did not increase the risks of tumor recurrence and development with SN in pure germinoma survivors.


Asunto(s)
Neoplasias Encefálicas , Germinoma , Hormona de Crecimiento Humana , Adolescente , Humanos , Germinoma/tratamiento farmacológico , Hormona del Crecimiento , Hormona de Crecimiento Humana/uso terapéutico , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Supervivientes de Cáncer
7.
BMC Endocr Disord ; 22(1): 23, 2022 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-35033046

RESUMEN

BACKGROUND: The differential diagnosis of IgG4-related hypophysitis and other inflammatory diseases or tumors involving sellar region is challenging even after sellar biopsy. Sellar germinoma is usually infiltrated by lymphocytes or plasma cells, and may be confused with hypophysitis. CASE PRESENTATION: A 36-year-old man with diabetes insipidus, elevated serum IgG4 level (336 mg/dl), and sellar mass was suspected to have IgG4-related hypophysitis, and no other lesion of IgG4-related disease was detected. After treated by prednisone and mycophenolate mofetil, the serum IgG4 decreased to 214 mg/dl. However, after withdrawal of the drugs, the IgG4 level increased to 308 mg/dl. Endocrine assessments revealed panhypopituitarism, and the sellar mass enlarged. Transsphenoidal sellar exploration and biopsy was conducted. Pathological examination showed that the lesion was germinoma with lymphocytes and plasma cells infiltration, and IgG4-staining was positive (70/HPF, IgG4/IgG ratio = 10%). The patient was then treated by cisplatin and etoposide. After four cycles of chemotherapy, the serum IgG4 was 201 mg/dl, and the sellar mass was invisible. CONCLUSION: Sellar germinoma can mimic the clinical characteristics of IgG4-related hypophysitis. Poor response to glucocorticoids can be used as an exclusion criterion in the clinical diagnosis of IgG4-related hypophysitis.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/diagnóstico , Germinoma/diagnóstico , Silla Turca , Adulto , Hipofisitis Autoinmune/diagnóstico , Neoplasias Encefálicas/tratamiento farmacológico , Cisplatino/administración & dosificación , Diagnóstico Diferencial , Etopósido/administración & dosificación , Germinoma/tratamiento farmacológico , Humanos , Inmunoglobulina G/sangre , Masculino
8.
Pediatr Blood Cancer ; 69(1): e29359, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34520101

RESUMEN

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.


Asunto(s)
Neoplasias Encefálicas , Germinoma , Neoplasias de Células Germinales y Embrionarias , Vinblastina , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/radioterapia , COVID-19 , Carboplatino/uso terapéutico , Niño , Etopósido/uso terapéutico , Femenino , Germinoma/tratamiento farmacológico , Germinoma/radioterapia , Humanos , Masculino , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/radioterapia , Pandemias , Vinblastina/uso terapéutico
9.
Neuro Oncol ; 24(8): 1389-1399, 2022 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-34935949

RESUMEN

BACKGROUND: This multinational study was conducted to report clinical presentations and treatment strategies in patients with intracranial germinomas across selected Asian centers, including failure patterns, risk factors, and outcomes. METHODS: A retrospective data collection and analysis of these patients, treated between 1995 and 2015 from eight healthcare institutions across four countries was undertaken. RESULTS: From the results, 418 patients were analyzed, with a median follow-up of 8.9 years; 79.9% of the patients were M0, and 87.6% had ß-human chorionic gonadotropin values <50 mIU/mL. The 5/10-year overall survival (OS) and recurrence-free survival (RFS) rates were 97.2%/96.2% and 89.9%/86.9%, respectively. RFS was predicted by the radiotherapy (RT) field, with focal RT having the worst outcome, whereas chemotherapy usage had no impact on survival. Among patients who received chemotherapy, response to chemotherapy did not predict survival outcomes. In M0 patients, primary basal ganglia tumors predicted a worse RFS. In patients with bifocal tumors, an extended field RT was associated with better outcomes. In multivariable analysis, only RT fields were associated with RFS. In relapsed patients, salvage rates were high at 85.7%. Additionally, patients who received salvage RT had a better outcome (91.6% vs. 66.7%). CONCLUSIONS: Survival outcomes of patients with germinoma were excellent. Thus, the focus of treatment for intracranial germinoma should be on survivorship. Further studies are warranted to find the optimal intensity and volume of radiation, including the role of chemotherapy in the survival of patients with intracranial germinomas, considering age, primary tumor location, and extent of disease.


Asunto(s)
Neoplasias Encefálicas , Germinoma , Glándula Pineal , Neoplasias Encefálicas/patología , Germinoma/tratamiento farmacológico , Germinoma/patología , Humanos , Glándula Pineal/patología , Estudios Retrospectivos , Terapia Recuperativa
10.
Cancer Rep (Hoboken) ; 5(8): e1586, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-34796700

RESUMEN

BACKGROUND: Intracranial germ cell tumors (GCTs) comprise 3%-5% of pediatric primary central nervous system (CNS) tumors in Western countries. Though they are related in embryonic origin to gonadal GCTs, which are considered highly treatable with cisplatin-based chemotherapy regimens, intracranial GCTs vary in malignant potential and sensitivity to radiation and chemotherapy, generally carrying a worse prognosis. Metastases of intracranial GCTs outside of the CNS are rare, indicate a poor prognosis, and their salvage treatment is not well established. CASE: A 15-year-old boy presented with bifocal (suprasellar and pineal) intracranial nongerminomatous germ cell tumors of mixed origin. The tumors were treated to full response with a multimodal approach of neoadjuvant chemotherapy, surgical resection, and adjuvant craniospinal proton radiation. Nine months following treatment completion, the patient presented with an enlarged cervical lymph node determined on excisional biopsy to be a recurrence of pure germinoma from the primary tumors. Salvage treatment involved high-dose chemotherapy and autologous stem cell transplantation; however, the patient denied further treatment prior to planned focal radiotherapy. Thirty months post-treatment, the patient is well with no evidence of recurrence. CONCLUSION: This case demonstrated the successful salvage treatment of an extraneural recurrence of an intracranial GCT using surgical resection and a high-dose chemotherapy and autologous stem-cell transplantation regimen, highlighting the unique factors which led to the selection of this regimen.


Asunto(s)
Neoplasias Encefálicas , Germinoma , Trasplante de Células Madre Hematopoyéticas , Neoplasias de Células Germinales y Embrionarias , Adolescente , Neoplasias Encefálicas/patología , Niño , Germinoma/tratamiento farmacológico , Germinoma/patología , Humanos , Ganglios Linfáticos/patología , Masculino , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Neoplasias de Células Germinales y Embrionarias/terapia , Trasplante Autólogo
11.
Neuro Oncol ; 24(6): 974-983, 2022 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-34850169

RESUMEN

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.


Asunto(s)
Neoplasias Encefálicas , Germinoma , Glándula Pineal , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/patología , Carboplatino/uso terapéutico , Niño , Preescolar , Etopósido , Germinoma/tratamiento farmacológico , Germinoma/patología , Germinoma/radioterapia , Humanos , Glándula Pineal/patología , Estudios Prospectivos , Adulto Joven
12.
Brain Dev ; 43(9): 967-971, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34092404

RESUMEN

BACKGROUND: Autoimmune mediated encephalitis (AME), which includes autoantibody-associated encephalitis and acute disseminated encephalomyelitis, is a common cause of encephalitis as well as infectious encephalitis in children. AME may be triggered by autoimmune responses to paraneoplastic syndromes and infections. Infectious encephalitis associated with an immunocompromised status caused by anti-cancer chemotherapy is well recognized; however, there have been few reports on the relationship between AME and chemotherapy. CASE REPORT: A ten-year-old previously healthy, developmentally normal girl was diagnosed with a pure germinoma in the suprasellar region. Following 30 days of induction chemotherapy, she developed a depressed level of consciousness with accompanying right hemiplegia, aphasia, and unexplained fever. Cerebrospinal fluid (CSF) analysis revealed positive oligoclonal bands and elevated neopterin levels. Neither atypical cells suggesting tumor exacerbation nor pathogens known to cause encephalitis were identified in the CSF. She was administrated immunosuppressive therapy and her symptoms rapidly improved. No known autoantibodies associated with autoantibody-associated encephalitis were identified in blood or CSF. However, the presence of oligoclonal bands and elevated neopterin levels in the CSF, and the favorable response to immunosuppressive therapy were consistent with an AME diagnosis. Thirteen days after the third course of chemotherapy, the patient developed a depressed level of consciousness again. Due to the recurrence of encephalitis, re-administration of immunosuppressive therapy was performed, which led to improvement in her symptoms. Recurrence of encephalitis has not occurred for 1 year after completion of chemotherapy. CONCLUSION: The chemotherapy-induced abnormal immune response might have triggered the AME.


Asunto(s)
Enfermedades Autoinmunes/inducido químicamente , Encefalitis/inducido químicamente , Encefalitis/diagnóstico , Germinoma/tratamiento farmacológico , Silla Turca , Niño , Quimioterapia , Femenino , Humanos , Neopterin/líquido cefalorraquídeo , Bandas Oligoclonales/líquido cefalorraquídeo
14.
Int J Radiat Oncol Biol Phys ; 108(3): 649-656, 2020 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-32502506

RESUMEN

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.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Germinoma/tratamiento farmacológico , Quimioterapia de Inducción/métodos , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundario , Carboplatino/administración & dosificación , Niño , Gonadotropina Coriónica Humana de Subunidad beta/sangre , Gonadotropina Coriónica Humana de Subunidad beta/líquido cefalorraquídeo , Irradiación Craneana , Ciclofosfamida/administración & dosificación , Etopósido/administración & dosificación , Estudios de Factibilidad , Femenino , Germinoma/metabolismo , Germinoma/radioterapia , Germinoma/secundario , Humanos , Quimioterapia de Inducción/efectos adversos , Masculino , Neutropenia/inducido químicamente , Proyectos Piloto , Supervivencia sin Progresión , Estudios Prospectivos , Terapia de Protones , Dosificación Radioterapéutica , Radioterapia Conformacional , Adulto Joven , alfa-Fetoproteínas/análisis , alfa-Fetoproteínas/líquido cefalorraquídeo
15.
Int J Radiat Oncol Biol Phys ; 108(3): 657-666, 2020 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-32434039

RESUMEN

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.


Asunto(s)
Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/radioterapia , Quimioradioterapia/métodos , Irradiación Craneoespinal/métodos , Germinoma/tratamiento farmacológico , Germinoma/radioterapia , Adolescente , Adulto , Anciano , Neoplasias Encefálicas/mortalidad , Quimioradioterapia/efectos adversos , Niño , Preescolar , Gonadotropina Coriónica Humana de Subunidad beta/sangre , Gonadotropina Coriónica Humana de Subunidad beta/líquido cefalorraquídeo , Irradiación Craneoespinal/tendencias , Craneotomía/métodos , Craneotomía/estadística & datos numéricos , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Germinoma/mortalidad , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/mortalidad , Neoplasias Inducidas por Radiación/etiología , Radioterapia/métodos , Radioterapia/tendencias , Dosificación Radioterapéutica , Enfermedades Raras/tratamiento farmacológico , Enfermedades Raras/mortalidad , Enfermedades Raras/radioterapia , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo , Insuficiencia del Tratamiento , Adulto Joven
16.
Chin Med J (Engl) ; 132(17): 2073-2078, 2019 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-31261204

RESUMEN

BACKGROUND: Rapid visual acuity (VA) decline was a common complaint in patients with sellar/suprasellar germinoma. In our hospital, 3.4 Gy/2f of emergency irradiation was applied to save patient VA and enable subsequent chemoradiotherapy. This study aimed to investigate the efficacy of emergency irradiation with 3.4 Gy/2f in patients with sellar/suprasellar germinoma who had rapid VA decline. METHODS: From January 2014 to December 2017, 33 patients with sellar/suprasellar germinoma who complained of VA decline within 3 months received 3.4 Gy/2f of emergency irradiation in Beijing Tiantan Hospital. The best-corrected VA (BCVA) and mean deviation (MD) were measured. Correlations between visual function change and clinical factors, including age at diagnosis, duration of VA decline, extent of tumor regression, serum level of tumor markers, were analyzed. RESULTS: Among 33 patients with sellar/suprasellar germinoma, the median diameter and volume of sellar/suprasellar lesions were 32 mm (range: 5-55 mm) and 12.9 cm (range 0.6-58.5 cm), respectively. Data on pre- and post-emergency-irradiation BCVA were obtained in 32 patients. For the right eyes, BCVA was improved in 23 patients (71.9%), unchanged in 7 (21.9%), and worsened in 2 (6.2%); and for the left eyes, these numbers were 27 (84.4%), 4 (12.5%), and 1 (3.1%), respectively. In terms of the logarithm of the minimum angle of resolution (logarithm of the minimum angle of resolution = Log (1/BCVA) score, the improvement was significant in both eyes (P < 0.001). In terms of MD, six patients had paired data and the improvement was marginal in the right eyes (P = 0.068) and significant in the left eyes (P = 0.043). However, no clinical factor was found to have correlation with visual function improvement. CONCLUSION: In sellar/suprasellar germinoma patients with VA decline, 3.4 Gy/2f of emergency irradiation was effective in improving visual function.


Asunto(s)
Germinoma/tratamiento farmacológico , Germinoma/terapia , Adolescente , Adulto , Niño , Preescolar , Gonadotropina Coriónica/metabolismo , Quimioterapia , Humanos , Radioterapia , Estudios Retrospectivos , Agudeza Visual/efectos de los fármacos , Agudeza Visual/fisiología , Agudeza Visual/efectos de la radiación , Adulto Joven
17.
Radiother Oncol ; 138: 180-186, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31319280

RESUMEN

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.


Asunto(s)
Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/radioterapia , Germinoma/tratamiento farmacológico , Germinoma/radioterapia , Adolescente , Adulto , Neoplasias Encefálicas/patología , Quimioterapia Adyuvante , Niño , Preescolar , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Germinoma/patología , Humanos , Masculino , Terapia Neoadyuvante , Recurrencia Local de Neoplasia , Glándula Pineal/patología , Pinealoma/tratamiento farmacológico , Pinealoma/patología , Pinealoma/radioterapia , Estudios Prospectivos , Inducción de Remisión , Estudios Retrospectivos , Tasa de Supervivencia , Adulto Joven
18.
Int J Radiat Oncol Biol Phys ; 104(4): 852-858, 2019 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-30940528

RESUMEN

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.


Asunto(s)
Neoplasias Encefálicas/radioterapia , Germinoma/radioterapia , Ventrículos Laterales/efectos de la radiación , Tratamientos Conservadores del Órgano , Lóbulo Temporal/efectos de la radiación , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Femenino , Germinoma/tratamiento farmacológico , Humanos , Masculino , Dosificación Radioterapéutica , Estudios Retrospectivos , Resultado del Tratamiento
19.
Clin Neurol Neurosurg ; 176: 15-18, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30476699

RESUMEN

BACKGROUND: Germinomas are sensitive to radiotherapy and chemotherapy. However, there has been no report involving in the potential therapeutic effect of dopamine agonists (DAs) such as bromocriptine on germinomas. CASE DESCRIPTION: A 20-year-old female was presented with bitemporal visual disturbance and amenorrhea. Magnetic resonance imaging demonstrated a huge sellar tumor with upward extension and invasion of the parasellar region. The blood tests showed an exceedingly high level of prolactin. A sellar tumor with hyperprolactinemia was diagnosed, and bromocriptine was initially given. After three months, the tumor volume had been obviously decreased by 82%. However, the tumor re-grew after ten months and the endoscopic endonasal surgery was performed. Histopathological and immunohistochemical examination indicated the patient had a pure sellar germinoma. The tumor cells strongly expressed dopamine 2 receptor and dopamine 5 receptor, which located in the membrane and cytoplasm. CONCLUSIONS: The transient but significant partial responsiveness of germinoma to bromocriptine treatment in this patient is a novel discovery, suggesting that DAs may be a potential therapeutic choice for tumors with the expression of dopamine 2/5 receptors.


Asunto(s)
Neoplasias Encefálicas/tratamiento farmacológico , Bromocriptina/uso terapéutico , Agonistas de Dopamina/uso terapéutico , Germinoma/tratamiento farmacológico , Receptores Dopaminérgicos/efectos de los fármacos , Femenino , Humanos , Neoplasias Hipofisarias/tratamiento farmacológico , Prolactina/sangre , Adulto Joven
20.
J Neurooncol ; 137(1): 77-82, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29177595

RESUMEN

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.


Asunto(s)
Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/radioterapia , Germinoma/tratamiento farmacológico , Germinoma/radioterapia , Adolescente , Adulto , Antineoplásicos , Terapia Combinada , Bases de Datos Factuales , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Evaluación de Procesos y Resultados en Atención de Salud , Sistema de Registros , Resultado del Tratamiento , Adulto Joven
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