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 > 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.

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.

Long-term toxicity of high-dose sequential chemotherapy with autologous hematopoietic stem cells support in very high-risk early breast cancer patients (pts)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11101-11101
Author(s):  
A. Bernardi ◽  
C. Zamagni ◽  
S. Quercia ◽  
F. Massari ◽  
N. Cacciari ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
High Risk ◽  
Early Breast Cancer ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Sequential Chemotherapy ◽  
Haematopoietic Stem Cells

11101 Background: High-dose chemotherapy with autologous haematopoietic stem cells support (HDCT) in the adjuvant treatment of breast cancer has been abandoned by many, but it remains unclear the real role of this treatment and a meta-analysis of high-dose chemotherapy adjuvant trials is ongoing. Methods: Twenty-five consecutive high risk early breast cancer pts with at least 40 months of follow-up treated at our institution with HDCT are included in the present analysis. Median age was 44 (range 24–59 years) and 15 pts were premenopausal. The median number of axillary lymph-nodes metastases was 13 (range 3–49) and the pathological stage was IIB in one pt, IIIA in 3 pts, IIIB in one pt and IIIC in 20 pts. Estrogen and/or progesterone receptors were positive in 15 pts and both negative in 10 pts. The 10- year risk of relapse of pts with disease characteristics similar to those included in our study population is 80–85%. The HDCT regimen used was cyclophosphamide 7g/m2 plus G-CSF (followed by apheresis of peripheral haematopoietic stem cells), methotrexate 8 g/m2 followed by thiotepa 600 mg/m2 and melphalan 160 mg/m2 or by mitozantrone 60 mg/m2 and melphalan 180 mg/m2 and stem cells reinfusion. Results: At a median follow-up of 7 years (range 3,5 - 8 years) 13 pts (52%) relapsed and 10 pts (40%) died. The most common sites of recurrence were lung, liver and bones; 6 pts developed brain metastases and in 2 cases a bone marrow infiltration was documented. No toxic deaths and no long term toxicities, except irreversible amenorrhoea in all the premenopausal pts, were observed. No secondary malignancies occurred.The median relapse-free survival is 65,1 months, while the median overall survival has not been reached yet. Conclusions: In our experience high-dose sequential chemotherapy with autologous stem cells support is a safe treatment with no toxic deaths and no long-term toxicities. This regimen should therefore be further investigated if translational research will be able to identify subgroups of pts with the highest probability to benefit from intensive chemotherapy. No significant financial relationships to disclose.

Long-term health status of high-risk neuroblastoma survivors treated with high-dose chemotherapy and hematopoietic stem cell transplantation.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 10054-10054 ◽  
Author(s):  
Sandrine Haghiri ◽  
Chiraz Fayech ◽  
Christelle Dufour ◽  
Claudia Pasqualini ◽  
Stephanie Bolle ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Second Cancers

10054 Background: Current treatment strategies including high-dose chemotherapy with stem cell transplantation rescue (HDC-SCT) have improved 5-year event-free survival for high-risk neuroblastoma (HRNB) patients, but with an increased risk of late treatment-related toxicities. Methods: Between 1980 and 2012, 439 children were treated for HRNB with HDC-SCT in Gustave Roussy (GR), among which 145 were alive and disease-free at 5-year post-SCT. Long-term health data have been collected for those 145 patients, prospectively within the long-term follow-up clinic in GR or retrospectively from pediatric consultations. Results: With a median follow-up post-SCT of 15 years (range 5-34), we observed 6 late relapses, 11 second cancers (including 3 papillary thyroid carcinomas; median delay = 20 years post-SCT [18-22]) and 9 deaths. Event-free and overall survival at 20-year post-SCT were 82% (95%CI = 70–90) and 89% (95%CI = 78–95), respectively. A second health event was observed in 135 patients (median = 3/patient), including 103 patients with at least 1 severe event (median = 1/patient). Cumulative incidence at 15-year post-SCT for second cancers is 4%, cardiac diseases 8%, thyroid 11%, renal 7%, hepatic focal nodular hyperplasia 14%, dental mal-development 70%, and severe hearing loss 20%. Height-for-age z-score was ≤-2 for 30 patients (21%) and ≤-3 for 12 patients (8%). After Busulfan-Melphalan conditioning regimen, 40/43 females and 33/35 males had a gonadal insufficiency. Conclusions: Long-term consequences of HRNB treatment including HDC are frequent and disabling, mainly due to hearing loss and gonadal insufficiency.

Allogeneic immunotherapy by hematopoietic stem cell transplantation (ASCT) after reduced intensity conditioning (RIC) following high-dose chemotherapy for patients with acute myeloblastic leukemia (AML) in first complete remission (CR1): Reduced toxicity

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7098-7098
Author(s):  
D. Blaise ◽  
R. Tabrizi ◽  
C. Faucher ◽  
M. Mohty ◽  
J. Bay ◽  
...  
Keyword(s):  
High Risk ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Intensive Chemotherapy ◽  
Hematopoietic Stem ◽  
Cell Counts ◽  
Probability Estimates ◽  
White Blood Cell Counts ◽  
Reduced Toxicity

7098 Background: RIC-based ASCT can be used after intensive chemotherapy in pts with CR1AML(Blaise, Cancer, 2005). Initial disease control was high and was not related to selection bias (Mohty, Leukemia, 2005).Here, we investigated if this control was maintained after a long follow-up. Methods: 37 pts (age: 51 (26–60)) with high risk clinical characteristics (70%) (Age = 50 (N=22, 59%); severe comorbidity (30%)) and/or poor risk leukemic features (65%) (Cytogenetics (35%); 2 induction courses (27%); secondary leukemia (11%), High white blood cell counts(14%) or partial remission (3%)) were treated. After CR1, pts received at least either 1 course of high dose cytarabine (24 g/m2) and anthracycline (HIDAC: N=21) or HIDAC + 1 course of. melphalan (140 mg/m2) (HDMEL) with auto-SCT Pts (HIDAC +HDM N=16). All pts were then scheduled to receive ASCT prepared with RIC (fludarabine (180 mg/m2), busulfan (8 mg/kg), Thymoglobulin (2.5 to 10 mg/kg)) followed with BMT (28%) or PBSC (72%). Results: With a Median follow-up of 3 years (16–70 mths). 15 pts experienced aGVHD (grade 2–4 aGVHD cumulative incidence (CI):22% (9–35). 10 and 14 pts presented a limited and extensive cGVHD respectively (CI cGVHD:65 % (50–80). 3 deaths were attributed to non-relapse causes (NRD) (AGVHD: 1; CGVHD: 2° (NRD CI: 8% (0–17). In all, 9 pts relapsed at 5 mths (2–19) (24% (9–35). Relapse was associated with the absence of cGVHD (cGVHD: 8 (0–19), no cGVHD 44% (12–76), p=.05). 25 pts are still alive in CR1 for overall survival and leukemia-free survival (LFS) probability estimates at 4 years of 65 % (48–79%) and 66% (49–80%) respectively. When restricting the analysis to the 33 pts evaluable for cGVHD, cGVHD remained the only independent risk factor positively influencing LFS (cGVHD: 81% (59–92); no cGVHD (56% (27–81), p=.05) Conclusions: We conclude that RIC Allo-SCT preceded by adequate prior intensive chemotherapy might offers a relatively low NRD while exerting a sustained leukemia control even in high risk pts deserving prospective evaluation against standard strategy of conventional Allo SCT. No significant financial relationships to disclose.

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.

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