scholarly journals Mpv Salvage Regimen Followed by Hdt/Asct and Whole Brain Irradiation for Secondary Cns Lymphoma: a Follow-Up Data

2014 ◽  
Vol 25 ◽  
pp. v83
Author(s):  
Ikuo Shimizu ◽  
Naoaki Ichikawa ◽  
Wataru Takeda ◽  
Toshimitsu Ueki ◽  
Yuki Hiroshima ◽  
...  
Keyword(s):  
Cns Lymphoma ◽  
Whole Brain Irradiation ◽  
Salvage Regimen ◽  
Whole Brain ◽  
Brain Irradiation

Treatment of primary CNS lymphoma with induction high-dose methotrexate, temozolomide, rituximab followed by consolidation cytarabine/etoposide: A pilot study with biomarker analysis

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7595-7595 ◽  
Author(s):  
S. Issa ◽  
J. Hwang ◽  
J. Karch ◽  
J. Fridlyand ◽  
M. Prados ◽  
...  
Keyword(s):  
Induction Therapy ◽  
Primary Cns Lymphoma ◽  
Cns Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Whole Brain Irradiation ◽  
Whole Brain ◽  
Brain Irradiation ◽  
Dose Methotrexate ◽  
Biomarker Analysis

7595 Background: There is currently no consensus on the optimal treatment for patients diagnosed with primary CNS lymphoma (PCNSL). Between 2001–2004, UCSF PCNSL patients were treated with combination high-dose methotrexate, temozolomide, rituximab (MTR) as induction therapy. Patients in CR with this regimen were treated with high-dose cytarabine plus etoposide as consolidation. The purposes of this study were: (1) Pilot analysis to determine the safety and efficacy of intensive methotrexate-based induction therapy followed by high-dose consolidation with elimination of whole brain irradiation; (2) Analysis of molecular markers in PCNSL which predict sensitivity to chemotherapy and outcome. Methods: 21 untreated, CD20 +, immunocompetent PCNSL patients were treated with combination methotrexate (8 gm/m²), temozolomide (150 mg/m²/day)and rituximab (375 mg/m²). Patients in CR received consolidation cytarabine (2 g/ m² x 8 doses) plus etoposide (40 mg/kg over 96 hours). IHC analysis of potential biomarkers predictive of outcome was performed on paraffin sections from these patients. Candidate markers for validation were selected by gene expression analysis of an independent, multicenter dataset of 20 cases. Results: Mean age was 58.6 y (range 40–81). Median KPS was 60. MTR and cytarabine/etoposide consolidation was well-tolerated with no treatment-related mortality or evidence for neurotoxicity. One case of post-remission cytopenia occurred after consolidation and resolved spontaneously. Eleven patients (52.4%) attained CR with induction; eight received consolidation; three patients in CR deferred consolidation. Median PFS was 11.5 months. Median OS for all 21 patients has not yet been reached with median follow-up of 27.5 months. Expression of the apoptotic regulator DAP-1 by lymphoma cells as determined by IHC was associated with improved PFS (p<0.028) and OS (p<0.021). Conclusions: Combination MTR followed by intensive consolidation appears to be well tolerated in PCNSL. PFS appears at least similar to regimens that contain whole brain irradiation. A larger phase II study has been initiated to evaluate this regimen in a multicenter setting. [Table: see text]

Astrocytoma in children: 14 years' experience at Stanford University Medical Center.

1988 ◽  
Vol 6 (6) ◽  
pp. 1001-1007 ◽  
Author(s):  
S Y Woo ◽  
S S Donaldson ◽  
R S Cox
Keyword(s):  
Adjuvant Chemotherapy ◽  
Medical Center ◽  
Histologic Grade ◽  
Current Therapy ◽  
Stanford University ◽  
Whole Brain Irradiation ◽  
Whole Brain ◽  
Brain Irradiation ◽  
High Histologic Grade

Between January 1, 1971 and December 31, 1984, 50 children (31 males, 19 females) ages 3 1/2 months to 18 years with primary CNS astrocytoma were seen in the Department of Therapeutic Radiology, Stanford University Medical Center. The actuarial survival and freedom from relapse (FFR) for the treated group is 46%, with a median follow-up of 7.2 years and a maximum follow-up of 14 years. The majority of relapses occurred within the first 2 years of diagnosis, and all relapses occurred at or adjacent to the initial site of tumor. Multivariate analysis revealed that factors correlated with poor survival are high histologic grade (including presence of necrosis) and primary tumor in the brain stem, while the only important prognostic factor associated with an adverse FFR is high histologic grade. Age, sex, degree of surgical resection, and total radiation dose to the tumor are not correlated with outcome. Patients with high-grade tumor were selected to receive whole brain irradiation and/or adjuvant chemotherapy; therefore, the findings of apparent poor prognosis associated with whole brain irradiation and adjuvant chemotherapy actually reflect patient selection. Current therapy is adequate for only half of children with astrocytoma. Thus, continued development of innovative therapies is indicated, particularly for those children with adverse prognostic factors.

Treatment of Primary CNS Lymphoma with Induction High-Dose Methotrexate, Temozolomide, Rituximab Followed by Consolidation Cytarabine/Etoposide: A Pilot Study with Biomarker Analysis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1364-1364 ◽  
Author(s):  
Samar Issa ◽  
Arthur Shen ◽  
Jon Karch ◽  
Cigall Kadoch ◽  
Marc Shuman ◽  
...  
Keyword(s):  
Overall Survival ◽  
Performance Status ◽  
Primary Cns Lymphoma ◽  
Immunohistochemical Analysis ◽  
Cns Lymphoma ◽  
High Dose ◽  
Whole Brain Irradiation ◽  
Whole Brain ◽  
Brain Irradiation ◽  
Biomarker Analysis

Abstract Background: There is no consensus on the optimal treatment for patients diagnosed with primary CNS lymphoma (PCNSL). The goals of this study were: to determine the safety and efficacy of a methotrexate (MTX)-based induction therapy followed by high-dose consolidation chemotherapy and the elimination or deferral of whole brain irradiation, to identify molecular markers in PCNSL which predict sensitivity to chemotherapy and outcome. Methods: 23 newly diagnosed, CD20-positive, immunocompetent PCNSL patients were treated with combination high-dose intravenous MTX (8 gm/m2), temozolomide (150 mg/m2/day) and intravenous rituximab (375 mg/m2) (MTR). Patients in complete remission (CR) after eight courses of MTX were offered consolidation with high-dose cytarabine (2 g/m2 x 8 doses) and etoposide (40 mg/kg over 96 hours) (AE). Candidate markers of outcome in PCNSL were identified by gene expression profile analysis of an independent, multicenter dataset of PCNSL tumors. Immunohistochemical analysis of one of these markers, death-associated protein-1 (DAP-1), was performed on paraffin sections of tumors from 18 of the patients treated with the MTR regimen. Results: MTR induction followed by AE consolidation was well tolerated with no treatment-related mortality or evidence for neurotoxicity. Thirteen patients (56.5%) attained CR with induction; 8 received consolidation; 5 in CR refused AE. Median progression-free (PFS) and overall survival (OS) has not yet been reached with a median follow-up of 33 months. Karnovsky performance status (KPS) correlated with improved survival (p<0.0281). Expression by lymphoma cells of DAP-1, a regulator of apoptosis, was associated with improved progression-free survival (p<0.03) and overall survival (p<0.038). Conclusions: Combination MTR followed by AE is well tolerated in PCNSL. PFS appears at least similar to regimens that contain whole brain irradiation. A multi-center study has been initiated to further evaluate this regimen. DAP-1 may be a tumor suppressor whose expression in PCNSL predicts a favorable response to MTX-based therapy.

scholarly journals P14.89 What happens after 15 years? A clinical picture of a cohort of survivors of CNS tumors treated with whole-brain irradiation in a National Cancer Center

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii88-iii89
Author(s):  
V L Espírito Santo ◽  
J Passos ◽  
T Pimentel ◽  
J Nunes ◽  
I Costa ◽  
...  
Keyword(s):  
Adult Survivors ◽  
Outcome Data ◽  
Adult Brain ◽  
Cancer Center ◽  
Cns Lymphoma ◽  
Normal Brain ◽  
Whole Brain Irradiation ◽  
Whole Brain ◽  
The Impact

Abstract BACKGROUND Radiotherapy (RT) is standard curative treatment for many tumours, specially brain tumours. However, RT causes damage to normal brain tissue due to genetic instability, impairment of synaptic plasticity and increased oxidative stress and inflammation. With improved treatment, patient survival also increased in years, making long-term effect of RT more evident. Late toxicities of RT are well described for pediatric survivors but there is scant literature on late toxicities in adult survivors and, in general, the adult brain is considered less susceptible to radiation damage. MATERIAL AND METHODS Retrospective analysis of adult patients treated with whole-brain RT with more than 15 years of follow-up. Clinical charts were reviewed to collect clinical, demographic and outcome data. RESULTS From 18 patients found (mean age at diagnosis of 27 years, 13 male/ 5 female), 5 were diagnosed with medulloblastoma, 5 CNS lymphoma, 5 with germinoma, 3 with ependymoma and 1 with teratocarcinoma. Most common presentations were headache (61,1%), seizure (16,7%) and dizziness (16,7%). 5 patients (27,8%) had hydrocephalus at diagnosis. All patients received whole-brain RT (mean 40Gys, varying between 21 to 60Gys), alongside with complete surgical resection in 11 patients (61,1%) and chemotherapy in 10 patients (55,6%). Mean follow-up time was 23,6 years and only 1 patient died due to lymphoma recurrence 16,7 years after the initial diagnosis. During follow-up, all patients had late RT induced changes, leukoencephalopathy in 16 patients (88,9%; mean 8,6 years after RT), ischemic stroke in 9 patients (50,0%; mean 16,0 years after RT), cerebral microbleeds in 14 patients (77,8%; mean 15,4 years after RT), cognitive decline in 12 patients (66,7%; mean 15,8 years after RT), radio-induced meningioma in 3 patients (16,7%; mean 18,1 years after RT) and epilepsy in 2 patients (11,1%; mean 10,5 years after RT). Also 1 patient had neurosensorial loss 14,2 years after RT and another one had subarachnoid haemorrhage due to ruptured aneurysm 19 years after RT. CONCLUSION Our results show that late RT induced effects are progressive and irreversible in the adult survivors, in a very similar manner as has been reported in the pediatric survivors. The impact on quality of live is increasing as patients survive longer. RT is still an important tool in neuro-oncology, but its role in curing brain tumors needs further study.

Randomized phase II trial on primary chemotherapy with high-dose methotrexate (HD-MTX) alone or associated with high-dose cytarabine (HD-araC) for patients with primary CNS lymphoma (I.E.L.S.G. #20 Trial): Tolerability, activity, and survival analyses

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8545-8545
Author(s):  
A. J. Ferreri ◽  
M. Reni ◽  
M. Martelli ◽  
G. Pangalis ◽  
M. Frezzato ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Primary Cns Lymphoma ◽  
Cns Lymphoma ◽  
High Dose ◽  
Whole Brain Irradiation ◽  
Brain Irradiation ◽  
Randomized Phase Ii ◽  
Ecog Ps

8545 Background: HD-MTX-based chemotherapy (cht) is the conventional approach to primary CNS lymphoma (PCNSL), but superiority of polycht over HD-MTX alone is unproven. A benefit of adding HD-araC to MTX has been suggested. This is a randomized phase II trial comparing HD-MTX monocht versus HD-MTX plus HD-araC as primary cht in immunocompetent patients (pts) with PCNSL. Methods: 79 HIV- pts with newly diagnosed PCNSL, age 18–75 ys, ECOG-PS≤3, and measurable disease were randomly assigned to receive 4 courses (interval 3 weeks) of MTX 3.5 g/mq (control arm; n=40) or MTX (same dose) + araC 2 g/mq × 2/d, d 2–3 (experimental arm; n=39). Cht was followed by whole-brain irradiation. Pts were stratified based on IELSG score and centre irradiation policy for pts >60 ys in complete remission (CR) after cht. CR rate (CRR) after cht was the primary endpoint; planned accrual (α=.05 β=.2) for P0 30% and P1 50% was 39 pts/arm. Results: Median age of the 79 entered pts was 58 ys (range 25–74). No differences in clinical presentation between arms were observed. Two hundred thirty-one (73%) of the 316 planned courses were actually delivered (MTX 71%; MTX+araC 76%). Causes of cht interruption were: progressive disease in 20 MTX and 8 MTX+araC pts, toxicity in 1 MTX and 7 MTX+araC pts and refusal in 2 MTX+araC pts. As expected, neutropenia, thrombocytopenia and infections were more common in MTX+araC arm. All G3–4 non-hematological toxicities were <5%. One MTX pt and 3 MTX+araC pts died of toxicity. CRR was 18% after MTX and 46% after MTX+araC (p=0.006), with an ORR of 40% and 69% (p=0.009), respectively. At a median follow-up of 30 m., 31 MTX and 22 MTX+araC pts experienced failure, with a 3-yr FFS of 21±6% and 38±8% (p=0.01), respectively. No differences in relapse sites or salvage efficacy between treatment arms were observed. Twelve MTX and 20 MTX+araC pts are alive, with a 3-yr OS of 32±8% and 46±9% (p=0.07). Conclusions: This is the first randomized trial on PCNSL with completed accrual. The addition of HD-araC to HD-MTX resulted in significantly better outcome and acceptable toxicity. MTX+araC may be the cht combination used as control arm in future randomized trials. No significant financial relationships to disclose.

Factors affecting functional outcomes in long-term survivors of intracranial germinomas: a 20-year experience in a single institution

2013 ◽  
Vol 11 (4) ◽  
pp. 454-463 ◽  
Author(s):  
Shinya Jinguji ◽  
Junichi Yoshimura ◽  
Kenichi Nishiyama ◽  
Hiroshi Aoki ◽  
Keisuke Nagasaki ◽  
...  
Keyword(s):  
Surgical Complications ◽  
Childhood Onset ◽  
Whole Brain Irradiation ◽  
Whole Brain ◽  
Factors Affecting ◽  
Brain Irradiation ◽  
Neurocognitive Functions ◽  
Late Adverse Effects

Object Radiation monotherapy—prophylactic craniospinal or whole-brain irradiation paired with a radiation boost to the primary tumor—is the standard treatment for intracranial germinomas at the authors' institution. The authors assessed long-term outcomes of patients with germinoma who underwent therapy and identified factors affecting them. Methods The authors retrospectively analyzed data obtained in 46 patients (35 males and 11 females, age 5–43 years at diagnosis) who had been treated for intracranial germinomas between 1990 and 2009 at the authors' institution. Thirty patients had germinomas in localized regions and 16 in multiple regions. Thirty-eight patients (83%) underwent radiotherapy alone (craniospinal irradiation in 32 and whole-brain irradiation in 6). Seven patients underwent radiochemotherapy and 1 underwent chemotherapy alone. The mean radiation doses for the whole brain, spine, and primary tumor site were 26.9, 26.6, and 49.8 Gy, respectively. The median follow-up period was 125 months. Results The 10-year overall and recurrence-free survival rates were 93.3% and 89.3%, respectively. None of the 38 patients who received radiation monotherapy developed a recurrent lesion, whereas 1 of 7 who underwent radiochemotherapy and the 1 patient who underwent chemotherapy had a recurrent lesion. Of the entire population, 26 patients required hormone replacement therapy, 2 had short stature, and 1 developed a radiation-induced meningioma. Seventeen of the 25 childhood- or adolescent-onset patients were 19 years or older at the latest follow-up visit, 15 of whom graduated from senior high school, and only 2 of whom graduated from college. Of 34 patients who were 19 years or older at the latest visit, 4 were students, 18 worked independently, 4 worked in sheltered workplaces, and 8 were unemployed. Of the 34 patients, 4 got married after the initial treatment, 3 of whom had children. There were 8 patients (17%) with low postoperative Karnofsky Performance Scale (KPS) scores that were significantly associated with impaired neurocognitive functions, severe surgical complications, and neurological impairments. In 10 of the 46 patients, KPS scores at the latest visit were lower than their postoperative KPS scores. These decreases in KPS scores were significantly correlated with a delayed decline in neurocognitive functions in childhood-onset patients and a postoperative impairment of neurocognitive functions in patients with adolescent- or adult-onset germinoma. Conclusions No tumor recurrence occurred in germinoma patients treated with the authors' radiation monotherapy, which appears to be effective enough to cure the tumor. Brain damage caused by tumors themselves and surgical complications were found to adversely affect functional outcomes in patients regardless of their age. Although radiotherapy rarely caused late adverse effects in patients with adolescent- or adult-onset, in some childhood-onset lesions, the radiation seems to carry the risk of neurocognitive dysfunctions, which are attributable to late adverse effects. Accordingly, treatments for germinoma patients should be selected according to a patient's age and the extent of the tumor and with particular care to avoid surgical complications.

Primary central nervous system lymphoma

1985 ◽  
Vol 62 (4) ◽  
pp. 522-527 ◽  
Author(s):  
Yasuto Kawakami ◽  
Kazuo Tabuchi ◽  
Rinkichi Ohnishi ◽  
Shoji Asari ◽  
Akira Nishimoto
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Subtotal Resection ◽  
Cns Lymphoma ◽  
Whole Brain Irradiation ◽  
Whole Brain ◽  
Content Type ◽  
Brain Irradiation

✓ A retrospective analysis of 21 cases of primary central nervous system (CNS) lymphoma is reported. All patients presented with a solitary mass in the supratentorial region. None had previously received immunosuppressive therapy. Neuroradiological studies included technetium-99m-pertechnetate brain scanning in eight cases, cerebral arteriography in all 21 cases, and computerized tomography (CT) in 14 cases. The characteristic features were increased uptake in brain scans, mass effect in arteriograms, and marked contrast enhancement on CT scans. Abnormal tumor vessels were occasionally seen on arteriography, and subtraction films were usually required to appreciate tumor stain. All patients underwent craniotomy, and histological studies of the tumors showed a diffuse type of lymphoma in all cases. Immunoglobulin testing was performed in 19 cases and a monoclonal spike was verified in 10, suggesting a B cell origin. All patients were followed until their death except one who was still alive 12 months from onset of symptoms. Therapy included subtotal resection in all 21 cases, whole-brain irradiation in six cases, chemotherapy in two cases, and a combination of whole-brain irradiation and chemotherapy in nine cases. Three different forms of chemotherapy were used. The results suggest that chemotherapy is an important addition to subtotal resection and whole-brain irradiation in the treatment of primary CNS lymphoma.

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