scholarly journals SEOM clinical guideline for management of adult medulloblastoma (2020)

2021 ◽  
Author(s):  
R. Luque ◽  
M. Benavides ◽  
S. del Barco ◽  
L. Egaña ◽  
J. García-Gómez ◽  
...  
Keyword(s):  
Residual Tumor ◽  
Large Cell ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Molecular Alterations ◽  
Adult Medulloblastoma ◽  
Group 4 ◽  
Risk Patients ◽  
Standard Risk

AbstractRecent advances in molecular profiling, have reclassified medulloblastoma, an undifferentiated tumor of the posterior fossa, in at least four diseases, each one with differences in prognosis, epidemiology and sensibility to different treatments. The recommended management of a lesion with radiological characteristics suggestive of MB includes maximum safe resection followed by a post-surgical MR < 48 h, LCR cytology and MR of the neuroaxis. Prognostic factors, such as presence of a residual tumor volume > 1.5 cm2, presence of micro- or macroscopic dissemination, and age > 3 years as well as pathological (presence of anaplastic or large cell features) and molecular findings (group, 4, 3 or p53 SHH mutated subgroup) determine the risk of relapse and should guide adjuvant management. Although there is evidence that both high-risk patients and to a lesser degree, standard-risk patients benefit from adjuvant craneoespinal radiation followed by consolidation chemotherapy, tolerability is a concern in adult patients, leading invariably to dose reductions. Treatment after relapse is to be considered palliative and inclusion on clinical trials, focusing on the molecular alterations that define each subgroup, should be encouraged. Selected patients can benefit from surgical rescue or targeted radiation or high-dose chemotherapy followed by autologous self-transplant. Even in patients that are cured by chemorradiation presence of significant sequelae is common and patients must undergo lifelong follow-up.

scholarly journals MBCL-28. LONG-TERM FOLLOW-UP RESULTS OF REDUCED DOSE CRANIOSPINAL RADIOTHERAPY AND TANDEM HIGH-DOSE CHEMOTHERAPY IN PATIENTS WITH HIGH-RISK MEDULLOBLASTOMA

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii394-iii394
Author(s):  
Ji Won Lee ◽  
Do Hoon Lim ◽  
Meong Hi Son ◽  
Ki Woong Sung ◽  
Hee Won Cho ◽  
...  
Keyword(s):  
High Risk ◽  
Cumulative Incidence ◽  
Residual Tumor ◽  
Large Cell ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Progression Rate ◽  
Reduced Dose ◽  
Craniospinal Radiotherapy

Abstract BACKGROUND In this study, we report the follow-up results of reduced-dose of craniospinal radiotherapy (CSRT) followed by tandem high-dose chemotherapy (HDCT) in patients with high-risk medulloblastoma (MB). METHODS Newly diagnosed high-risk MB patients (metastatic disease, postoperative residual tumor &gt; 1.5 cm2 or large cell/anaplastic histology) over 3 years of age were enrolled in this study. Two cycles of pre-RT chemotherapy, RT including reduced-dose CSRT (23.4 or 30.6 Gy), 4 cycles of post-RT chemotherapy and tandem HDCT were given. NanoString and DNA sequencing were done with archival tissues. RESULTS Forty patients were enrolled, and molecular subgrouping was possible in 21 patients (2 WNT, 3 SHH, 8 Group 3 and 8 group 4). All patients including two patients who experienced progression during the induction chemotherapy underwent HDCT. Relapse/progression occurred only in four patients (10-year cumulative incidence 10.4 ± 0.3%). However, six patients died from treatment-related mortality (TRM) (4 acute TRMs and 2 late TRMs) resulting in 18.5 ± 0.5% of 10-year cumulative incidence. Taken together, the 10-year event-free survival and overall survival were 71.1 ± 8.0% and 68.9 ± 8.5%, respectively. Late effects were evaluated in 25 patients and high-tone hearing loss, endocrine dysfunction, dyslipidemia, and growth retardation were common. CONCLUSIONS Strategy using tandem HDCT following reduced-dose CSRT showed promising results in terms of low relapse/progression rate, however, the high TRM rate indicates that modification of HDCT regimen and careful selection of patients who can have benefit from HDCT will be needed in the future study.

Risk Adapted BEACOPP Regimen Based on Early Scintigraphy Can Reduce the Cumulative Dose of Chemotherapy for Standard and High Risk Hodgkin Lymphoma (HD) with No Impairment of Outcome.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 815-815
Author(s):  
Eldad J. Dann ◽  
Rachel Bar Shalom ◽  
Nissim Haim ◽  
Ada Tamir ◽  
Menachem Ben Shachar ◽  
...  
Keyword(s):  
High Risk ◽  
High Dose Chemotherapy ◽  
Stage I ◽  
Stage Iii ◽  
High Dose ◽  
Eligibility Criteria ◽  
Risk Patients ◽  
A Prospective Study ◽  
Standard Risk

Abstract A prospective study evaluating the outcome of HD pts whose chemotherapy was tailored based on results of scans performed after 1or 2 cycles of chemotherapy reducing the cumulative chemotherapy for early responders and maximizing the dose for late responders. Study was initiated in 1999 for patients with classical HD age 18–65y. Eligibility criteria were either stage I, II with unfavorable features (see table) or any stage III or IV HD. Those with I-II B or bulky or any Stage III-IV were defined according to IPS. Patients with standard risk were treated with 2 cycles of standard BEACOPP (SB). Those with high risk were treated with 2 cycles of escalated BEACOPP (EB). GA67 or FDG PET scan was performed at diagnosis and after the 1st or 2nd cycle for 57 and 55 pts respectively. If the early scan remained positive then additional 4 cycles of EB were administered, otherwise, SB was given. 108 pts 44 F64 M age 18–63y (median 33) who had at least 1 year of follow up are reported. The CR rate was 97%. The 4-yr disease free (DFS) and overall survival (OS) is 84% and 90% respectively at a median follow up of 35-month (5-70). The 4-yr DFS and OS are similar for standard and high risk patients. The disease progressed in 3/10 pts with an interim positive PET versus 1/40 negative scans (p&lt;0.03) and in 1/13 (8%) interim positive Ga67scan versus 7/44 (16%) negative scan (NS). Negative predictive value of early normal PET and GA67 scans are 98% and 84% respectively. Only one patient developed secondary leukemia following salvage therapy and high dose chemotherapy. One patient died during therapy from unrelated cause. Conclusion: PET is a useful tool for early interim decision regarding dose of chemotherapy. Early PET allowed for chemotherapy reduction in 80% of high-risk pts. Only 14% of standard risk patients required dose intensification. Similar DFS and OS can be obtained regardless of IPS. 6 cycles of risk adapted BEACOPP are effective. Standard Risk High Risk Standard BEACOPP Escalated BEACOPP Stage I, II ≥ Age 50yrs; ≥ 4 sites; “B” symptoms or Bulky, stage III,IV IPS 0-2 IPS 3-7

scholarly journals Randomized trial comparing standard vs sequential high-dose chemotherapy for inducing early CR in adult AML

2019 ◽  
Vol 3 (7) ◽  
pp. 1103-1117 ◽  
Author(s):  
Renato Bassan ◽  
Tamara Intermesoli ◽  
Arianna Masciulli ◽  
Chiara Pavoni ◽  
Cristina Boschini ◽  
...  
Keyword(s):  
High Risk ◽  
Odds Ratio ◽  
High Dose Chemotherapy ◽  
Hazard Ratio ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Risk Patients ◽  
Standard Risk

Abstract Here we evaluated whether sequential high-dose chemotherapy (sHD) increased the early complete remission (CR) rate in acute myelogenous leukemia (AML) compared with standard-intensity idarubicin-cytarabine-etoposide (ICE) chemotherapy. This study enrolled 574 patients (age, 16-73 years; median, 52 years) who were randomly assigned to ICE (n = 286 evaluable) or sHD (2 weekly 3-day blocks with cytarabine 2 g/m2 twice a day for 2 days plus idarubicin; n = 286 evaluable). Responsive patients were risk-stratified for a second randomization. Standard-risk patients received autograft or repetitive blood stem cell-supported high-dose courses. High-risk patients (and standard-risk patients not mobilizing stem cells) underwent allotransplantation. CR rates after 2 induction courses were comparable between ICE (80.8%) and sHD (83.6%; P = .38). sHD yielded a higher single-induction CR rate (69.2% vs 81.5%; P = .0007) with lower resistance risk (P &lt; .0001), comparable mortality (P = .39), and improved 5-year overall survival (39% vs 49%; P = .045) and relapse-free survival (36% vs 48%; P = .028), despite greater hematotoxicity delaying or reducing consolidation blocks. sHD improved the early CR rate in high-risk AML (odds ratio, 0.48; 95% confidence interval [CI], 0.31-0.74; P = .0008) and in patients aged 60 years and less with de novo AML (odds ratio, 0.46; 95% CI, 0.27-0.78; P = .003), and also improved overall/relapse-free survival in the latter group (hazard ratio, 0.70; 95% CI, 0.52-0.94; P = .01), in standard-risk AML, and postallograft (hazard ratio, 0.61; 95% CI, 0.39-0.96; P = .03). sHD was feasible, effectively achieved rapid CR, and improved outcomes in AML subsets. This study is registered at www.clinicaltrials.gov as #NCT00495287.

Outcome in 41 patients with late relapse germ cell tumors (GCT) treated with high-dose chemotherapy (HDCT)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5086-5086
Author(s):  
A. Lorch ◽  
O. Rick ◽  
J. T. Hartmann ◽  
B. Metzner ◽  
A. Glasmacher ◽  
...  
Keyword(s):  
Tumor Markers ◽  
Germ Cell Tumors ◽  
Residual Tumor ◽  
High Dose Chemotherapy ◽  
Phase Iii ◽  
Late Relapse ◽  
High Dose ◽  
Multifocal Disease ◽  
Very High

5086 Background: The management of patients (pts) with late-relapse GCT and unresectable tumors or very high tumor markers is controversial. Methods: A total of 41 late-relapse pts were identified among a group of 216 pts with refractory or relapsed GCT who were treated in an open, prospective, randomized, multicenter phase III trial. Late relapse was defined as any relapse occurring more than 2 years after completion of initial chemotherapy for GCT. Treatment consisted of either one cycle cisplatin 100 mg/m2, etoposide 375 mg/m2 and ifosfamide 6 g/m2 (VIP) plus three cycles of high-dose carboplatin 1,500 mg/m2 and etoposide 1,500 mg/m2 (CE, arm A) or of three cycles of VIP plus one cycle high-dose carboplatin 2,200 mg/m2, etoposide 1,800 mg/m2 and cyclophosphamide 6,400 mg/m2 (CEC, arm B). Each HDCT was followed by reinfusion of autologous peripheral blood progenitor cells. Results: Overall 20 pts with late-relapse GCT received sequential HDCT and 21 pts single HDCT when the study was stopped due to excess treatment-related mortality in arm B; median time to late relapse in 41 pts was 5.4 years (range 2–18 years); 8/41 (20%) pts had seminomatous GCT, 32/41 (78%) pts had nonseminomatous GCT with or without teratoma; one pt (2%) had unknown GCT histology. No non-GCT histologies were included. The retroperitonum was most commonly involved in 30/41 (73%) pts. 29 of 41 (71%) pts had unresectable, multifocal disease and 20/41 (49%) pts also had very high markers. A complete remission to chemotherapy alone was achieved in 4/41 (10%) pts, 16/41 (39%) pts achieved a partial remission with negative tumor markers. The remaining 21/41 (51%) either had a transient or no response despite HDCT. Residual tumor resections were performed in 17/41 (41%) pts. Residual tumor histology was viable cancer in 8/17 (47%) pts, teratoma in 4/17 (24%) pts and necrosis in 5/17 (25%) pts. With a minimum follow-up of 1 year and a median follow-up of 3 years the estimated Kaplan-Meier rates are 17%, 20% and 32% for event-free, progression-free and overall survival. Conclusion: Treatment outcome after HDCT was inferior in late-relapse pts compared to the group of pts who relapsed within less than 2 years. Despite an overall poor prognosis, HDCT can still result in long-term remissions in selected late-relapse GCT pts. No significant financial relationships to disclose.

Nivolumab and brentuximab vedotin (BV)-based, response‐adapted treatment in children, adolescents, and young adults (CAYA) with standard-risk relapsed/refractory classical Hodgkin lymphoma (R/R cHL): Primary analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8013-8013
Author(s):  
Peter D. Cole ◽  
Christine Mauz-Körholz ◽  
Maurizio Mascarin ◽  
Gérard Michel ◽  
Stacy Cooper ◽  
...  
Keyword(s):  
Metabolic Response ◽  
High Dose Chemotherapy ◽  
Brentuximab Vedotin ◽  
High Dose ◽  
Primary Analysis ◽  
Immune Mediated ◽  
Phase 2 Study ◽  
Report Data ◽  
Standard Risk

8013 Background: Outcomes for younger patients (pts) with R/R cHL are poor, particularly for those without complete metabolic response (CMR) before autologous transplant (auto-HCT). Nivolumab + BV has shown 67% CMR and a high 2-y PFS rate as first salvage in adults with R/R cHL. CheckMate 744 (NCT02927769) is an ongoing phase 2 study for CAYA with R/R cHL, evaluating a risk-stratified, response-adapted approach using nivolumab + BV and, for pts without CMR, BV + bendamustine. In the initial analysis of the standard-risk cohort (R2), the regimen was well tolerated with high CMR rates before consolidation with high-dose chemotherapy plus auto-HCT. We report data from the primary analysis. Methods: Pts were aged 5–30 y and had first-line treatment (tx) without auto-HCT. Risk stratification has been described previously (Harker-Murray, ASH 2018). Pts received 4 induction cycles of nivolumab + BV; pts without CMR by blinded independent central review (BICR) received BV + bendamustine intensification. Pts with CMR at any time could proceed to consolidation off study. Response was per Lugano 2014 criteria. Primary endpoint: CMR rate (Deauville ≤3) per BICR any time before consolidation. Results: At database lock, 44 pts were treated in R2 (median follow up: 20.9 mo); 43 received 4 induction cycles and 11 received intensification. Median age was 16 y (range 9–30); 24 (55%) pts had primary refractory cHL and 20 had relapsed cHL. CMR rates and ORR any time before consolidation and after induction are shown in Table. 1-y PFS rate by BICR was 91% (90% CI 77–96). During induction, 8 (18%) pts experienced grade (G) 3–4 tx-related adverse events (TRAEs); the most common any grade TRAEs were nausea and hypersensitivity (20% each). 1 TRAE led to discontinuation (G3 anaphylaxis). Most tx-related immune-mediated AEs were G1–2 (1 pt had 2 G3 infusion-related reactions). Conclusions: This risk-stratified, response-adapted approach offers a well-tolerated salvage strategy with high CMR rates and no new safety signals for CAYA with R/R cHL. Most pts avoided alkylator exposure prior to consolidation. Further follow up may confirm durability of disease control. Clinical trial information: NCT02927769 . [Table: see text]

scholarly journals LINC-15. OUTCOME OF CHINESE CHILDREN WITH MEDULLOBLASTOMA: A MULTI-CENTER EXPERIENCE WITH RISK-ADAPTED THERAPY

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii381-iii381
Author(s):  
Xiaofei Sun ◽  
Anthony Pak-Yin Liu ◽  
Qunying Yang ◽  
Jian Wang ◽  
Shaoxiong Wu ◽  
...  
Keyword(s):  
High Risk ◽  
Residual Tumor ◽  
Large Cell ◽  
High Dose ◽  
Average Risk ◽  
Group 4 ◽  
High Risk Disease ◽  
Significant Difference ◽  
Oncology Care ◽  
Group 3

Abstract BACKGROUND Medulloblastoma is the commonest brain tumor in young children but literature on Chinese is scarce. We hereby present the outcome of children with medulloblastoma managed according to a risk- and age-stratified guideline from ten institutions across China. METHODS Patients &lt;18 years of age diagnosed with medulloblastoma between January 2016 and April 2019 were reviewed. Patients ≥3 years, stratified into average-risk (≤1.5cm2 residual tumor, non-metastatic, non-anaplastic histology) and high-risk (others) groups, were treated with risk-adapted craniospinal irradiation (average-risk: 23.4Gy, high-risk: 36Gy), tumor boost, and chemotherapy (lomustine/cisplatin/vincristine). Patients &lt;3 years (considered high-risk, other than patients with localized and desmoplastic/nodular histology) received chemotherapy (cyclophosphamide/vincristine, high-dose methotrexate, carboplatin/etoposide) with/without delayed irradiation. RESULTS 112 patients were included with a median age at diagnosis of 6.5 years (range: 0.5–16.7). 16 patients (14.3%) had residual tumor &gt;1.5cm2 and 36 (32%) had metastasis. Available data on histological subtype (n=87) were classic in 56 (64%), desmoplastic/nodular or extensive nodularity in 23 (26%), and large cell/anaplastic in 8 (9%). Molecular subgrouping (n=55) assigned tumors as WNT-activated (n=8, 15%), SHH-activated (n=17, 31%), Group 3 (n=12, 22%) and Group 4 (n=18, 33%). Respective 2-year EFS/OS for patients ≥3 and &lt;3 years were 86.0±4.0%/96.4±2.1% and 57.8±12.6%/81.4±9.8% (EFS/OS p&lt;0.001/p=0.009). Significant difference in outcome was also observed between patients with average-risk and high-risk disease (EFS/OS p=0.006/p=0.018). CONCLUSION We demonstrated feasibility in protocolizing the inter-disciplinary treatment for medulloblastoma in China. This will serve as a prototype for the standardization of pediatric neuro-oncology care in the country.

Long-term neuropsychological follow-up of young children with medulloblastoma treated with sequential high-dose chemotherapy and irradiation sparing approach

2017 ◽  
Vol 133 (1) ◽  
pp. 119-128 ◽  
Author(s):  
Taryn B. Fay-McClymont ◽  
Danielle M. Ploetz ◽  
Don Mabbott ◽  
Karin Walsh ◽  
Amy Smith ◽  
...  
Keyword(s):  
Young Children ◽  
High Dose Chemotherapy ◽  
High Dose
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