High-Producer Haplotypes of Tumor Necrosis Factor Alpha and Lymphotoxin Alpha Are Associated With an Increased Risk of Myeloma and Have an Improved Progression-Free Survival After Treatment

2000 ◽  
Vol 18 (15) ◽  
pp. 2843-2851 ◽  
Author(s):  
Faith E. Davies ◽  
Sara J. Rollinson ◽  
Andrew C. Rawstron ◽  
Eve Roman ◽  
Stephen Richards ◽  
...  
Keyword(s):  
Overall Survival ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Necrosis Factor Alpha ◽  
Free Survival ◽  
Increased Risk ◽  
Factor Alpha ◽  
Lymphotoxin Alpha ◽  
Necrosis Factor

PURPOSE: To determine the effect of polymorphic variations in the tumor necrosis factor alpha (TNFα) and lymphotoxin alpha (LTα) genes on the predisposition to myeloma and the effect of these polymorphisms on response to treatment and overall survival. PATIENTS AND METHODS: Genotype distribution was determined in 63 patients with monoclonal gammopathy of uncertain significance (MGUS) and 198 patients with myeloma and compared with that in 250 age- and sex-matched population-based controls. The effect on treatment response and survival was determined in 171 myeloma patients treated with either conventional or high-dose chemotherapy. RESULTS: Comparison of the extended TNFα/LTα haplotype in the myeloma cases and controls showed a significant excess of high-producer alleles in the cases. The double heterozygotes TNF1/2 and LT10.5/5.5 were present in 35.8% of cases but in only 18% of the controls; this presence was associated with a significant increased risk of myeloma (odds ratio, 2.05; 95% confidence interval, 1.26 to 3.35). A similar odds ratio was seen in the MGUS cases, suggesting that this genotype is associated with the initiation of plasma-cell disorders rather than the progression of MGUS to myeloma. The median overall survival time of myeloma patients was 53.8 months and showed no difference with regard to TNFα/LTα polymorphic status. A trend toward an improved progression-free survival was apparent in cases with a high-producer haplotype, although this effect was seen only in patients receiving high-dose chemotherapy. CONCLUSION: Individuals with polymorphisms associated with a high production of TNFα/LTα are at a significantly increased risk of developing MGUS and myeloma. The impact of polymorphic status on overall survival is minimal, although there is a trend toward an increased progression-free survival in the high-producer group.

The Survival of Multiple Myeloma Patients: A Single Institution Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5223-5223
Author(s):  
Zwi N. Berneman ◽  
An-Sofie Verstraete ◽  
Alain Gadisseur ◽  
Ann Van de Velde ◽  
Wilfried A. Schroyens
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Conventional Chemotherapy ◽  
Free Survival

Abstract Background: For a long time, multiple myeloma has been a disease with a poor outcome. High dose (melphalan) chemotherapy followed by autologous stem cell transplantation has been reported to improve the overall and progression-free survival of these patients. Objective: To determine the survival of multiple myeloma patients treated with conventional chemotherapy and compare it with that of patients treated with high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation. Design/Methods: 83 myeloma patients treated at a single institution were included in this retrospective study. They were divided into two groups: one group of patients who were received high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (n=42) and one group of patients who only received conventional chemotherapy and were eventually also treated with thalidomide and/or corticosteroids (n=41). The distribution of the stages of the disease according to Salmon and Durie were similar in both groups of patients. For both groups, the overall and progression-free survival was calculated. Results: In the general analysis, myeloma patients who underwent an autologous transplant had a significantly longer overall survival (58.8 vs. 52.2 months, p=0.036) and progression-free survival (39.6 vs. 11.8 months, p < 0.001) in comparison with the conventional chemotherapy group. If analysis was restricted to those patients who were transplanted as a first-line treatment, there was no significant difference in overall survival in comparison with conventional chemotherapy (51.8 vs. 52.2 months, p= 0.422); progression-free survival was significantly better in the first-line transplant arm as compared to the conventional chemotherapy arm (35.4 vs. 11.8 months, p= 0.003). As the median age in the transplant arm was significantly lower than in the conventional chemotherapy arm, we also performed a sub-analysis of patients who were between 60 and 70 years of age at diagnosis; there was no significant difference in overall survival between the two groups (60.7 vs. 69.5 months, p= 0.656), while the progression-free survival was again better in the autologous transplant group as compared to the conventional chemotherapy group (41.0 vs. 8.4 months, p= 0.020). Conclusion: High-dose chemotherapy and autologous stem cell transplantation in the treatment of myeloma is associated with improved progression-free survival and in the general analysis, with improved overall survival. The overall survival of patients who were only treated with conventional chemotherapy is somewhat higher (more than 4 years) as compared to that of historical controls (2–3 years).

Risk Factors Associated with the Development of Pneumonitis After High-Dose Chemotherapy with Cyclophosphamide, BCNU, and Etoposide (CBV) Followed by Autologous Stem Cell Transplant

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 903-903
Author(s):  
Andrew A. Lane ◽  
Philippe Armand ◽  
Yang Feng ◽  
Donna Neuberg ◽  
Jeremy S. Abramson ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Stem Cell Transplant ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Free Survival ◽  
Mediastinal Radiation ◽  
Increased Risk

Abstract Abstract 903 Background: High-dose chemotherapy (HDC) with autologous stem cell transplant (ASCT) is a standard component of therapy for some patients with hematologic malignancies, particularly those with relapsed or refractory lymphoma. No high-dose chemotherapy regimen has been shown to be superior to another, and thus regimens are chosen based on institutional standards and toxicity profiles. Pneumonitis is a recognized complication of HDC regimens containing BCNU. There has not been a large study of uniformly-treated lymphoma patients to define the incidence and risk factors for developing pneumonitis in the modern era. Methods: We retrospectively examined the medical records of patients who were treated with HDC-ASCT at the Dana-Farber Cancer Institute and Massachusetts General Hospital Cancer Center from 2007–2009 using a regimen containing cyclophosphamide 750 mg/m2 Q12h x4d, BCNU 112.5 mg/m2 daily x4d, and VP-16 (etoposide) 200 mg/m2 Q12h x4d (CBV). Overall (OS) and progression-free survival (PFS), and the incidence of pneumonitis were determined. Univariable and multivariable analyses were performed for characteristics likely to be associated with an increased risk of pneumonitis, which was defined based on a combination of clinical, laboratory, and radiographic factors, with or without bronchoscopy. Results: 222 patients were analyzed. The age range was 21–77 (median 54). 61% were male. 71% had non-Hodgkin lymphoma and 29% had Hodgkin lymphoma. The median number of prior chemotherapy regimens was 2; 65% of patients had received prior rituximab, 31% prior bleomycin, and 12% prior gemcitabine. 71% had disease involvement of the mediastinum, and 11% had received prior mediastinal radiation therapy. 43% were past or present smokers. The median follow-up among all living patients was 12 months. The total cumulative incidence of pneumonitis was 22% (49 patients), with 41 patients (19%) receiving corticosteroid treatment, and 18 patients (8%) requiring inpatient hospitalization for pneumonitis. The time range to development of pneumonitis was 26–199 days post-transplant, with a median of 50 days. There were four treatment-related deaths (1.8%): three related to pneumonitis and one related to veno-occlusive disease. On univariable analysis, age, diagnosis of Hodgkin lymphoma, prior mediastinal radiation, prior bleomycin, total BCNU dose delivered, and lack of complete remission status at the time of ASCT were associated with the development of pneumonitis. Gender, body mass index, history of smoking, mediastinal disease involvement, prior rituximab, prior gemcitabine, and pretransplant pulmonary function testing were not found to be statistically significantly different between patients with and without pneumonitis. Stepwise multivariable logistic regression analysis, excluding 31 patients without pneumonitis who had death, relapse, or censoring in the first four months post-transplant, revealed the following variables as independently associated with development of pneumonitis: prior mediastinal radiation (odds ratio 6.5, 95% CI 2.2–18.9, P=0.0005), total BCNU dose above 1000 mg (OR 3.4, 95% CI 1.3–8.7, P=0.012), and age less than 54 (OR 3.0, 95% CI 1.4–6.5, P=0.0037). One year overall survival was 92%, and progression-free survival was 71%. There were no variables, including pneumonitis, associated with PFS on multivariable analysis. Only lack of complete or partial disease response prior to ASCT was associated with inferior OS on multivariable Cox regression modeling (hazard ratio 0.2, 95% CI 0.05–0.72, P=0.01). Conclusions: Pneumonitis is relatively common after HDC-ASCT using CBV conditioning. Increased vigilance for symptoms of pneumonitis is warranted for patients with prior mediastinal radiation and for younger patients. Our data suggests an increased risk with total BCNU dose above 1000 mg, suggesting a possible threshold toxicity effect. Empiric dose reduction may be considered for patients who would receive greater than 1000 mg of BCNU, particularly if they are also younger and/or have had prior mediastinal radiation. Disclosures: No relevant conflicts of interest to declare.

High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Support for Relapsed or Refractory Primary CNS Lymphoma - a Prospective Multicentre Trial By the German Cooperative PCNSL Study Group

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 781-781
Author(s):  
Benjamin Kasenda ◽  
Gabriele Ihorst ◽  
Roland Schroers ◽  
Agnieszka Korfel ◽  
Ingo GH Schmidt-Wolf ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Research Funding ◽  
Primary Cns Lymphoma ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
Cns Lymphoma ◽  
High Dose ◽  
Free Survival ◽  
High Dose Cytarabine

Abstract Purpose To investigate safety and efficacy of high-dose chemotherapy followed by autologous stem cell transplantation (HCT-ASCT) in patients with relapsed or refractory primary CNS lymphoma (PCNSL). Patients and methods We conducted a single-arm multicentre phase 2 study for immunocompetent patients (<66 years of age) with PCNSL failing prior HD-MTX based chemotherapy. Induction treatment consisted of 2 courses of rituximab (rituximab 375mg/m2), high-dose cytarabine (2 x 3g/m2) and thiotepa (40mg/m2) with collection of autologous stem cells in between. Conditioning treatment for HCT-ASCT consisted of rituximab 375mg/m2, carmustine 400mg/m2 and thiotepa (4 x 5mg/kg). Patients commenced HCT-ASCT irrespective of response status after induction. Only patients not achieving complete remission (CR) after HCT-ASCT received whole brain radiotherapy (WBRT). The primary endpoint was CR after HCT-ASCT by intention-to-treat (ITT). Secondary endpoints included safety, progression free survival (PFS, time to progression or death) and overall survival (OS, time to death due to any cause). Results Between May 2007 and July 2012, we enrolled 39 patients from 12 German centres. The median age and Karnofsky performance score was 57 years (range 37 to 65) and 90% (range 60% to 100%), respectively. 28 (71.8%) patients had relapsed and 8 (28.2%) refractory disease. 22 (56.4%) patients responded to induction (4 CR, 18 partial remissions [PR]) and 32 (82.1%) patients commenced HCT-ASCT. 22 patients (56.4%, 95% CI 39.6% to 72.2%) achieved CR after HCT-ASCT, 6 (15.4%) achieved PR, and 1 (2.6%) had stable disease. In 9 (17.8%) patients the final scan was not done, because 7 (18.0%) did not undergo HCT-ASCT and 2 died (5.1%) during HCT-ASCT procedure. After a median follow-up of 45.2 months, the respective 2-year PFS and OS rates were 46.0% (95% CI 30.3% to 61.7%, median PFS 12.4 months, Figure 1) and 56.4% (95% CI 40.8% to 72.0%); median OS not reached (Figure 2). The non-relapse mortality rate was 10.3% (95% CI 4.1% to 26.0%) at 1 year without any further increase afterwards. In the subset of 32 patients who received HCT-ASCT, 14 (56.3%) experienced progression or died translating into 1 and 2-year PFS rates (calculated from date of HCT-ASCT) of 62.5% (95% CI 45.7% to 79.3%) and 56.1% (95% CI 38.8% to 73.3%) with no further decrease afterwards. Main grade 3 or higher toxicities were hematological as expected. We recorded four (10.3%) treatment-related deaths, 2 during induction and 2 during HCT-ASCT. Conclusions In eligible PCNSL patients failing HD-MTX based chemotherapy, a short induction with high-dose cytarabine and thiotepa followed by HCT-ASCT is an effective treatment option. Our data provide a reliable benchmark for future comparative studies needed to further scrutinize the role of HCT-ASCT in the salvage setting for PCNSL. Figure 1. Progression free survival Figure 1. Progression free survival Figure 2. Overall survival Figure 2. Overall survival Disclosures Kasenda: Riemser: Other: Travel Support. Schmidt-Wolf:Janssen: Research Funding; Novartis: Research Funding. Röth:Alexion Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria. Stilgenbauer:Amgen: Consultancy, Honoraria, Other: Travel grants, Research Funding; Genentech: Consultancy, Honoraria, Other: Travel grants , Research Funding; Boehringer Ingelheim: Consultancy, Honoraria, Other: Travel grants , Research Funding; Janssen: Consultancy, Honoraria, Other: Travel grants , Research Funding; Hoffmann-La Roche: Consultancy, Honoraria, Other: Travel grants , Research Funding; Pharmacyclics: Consultancy, Honoraria, Other: Travel grants , Research Funding; Novartis: Consultancy, Honoraria, Other: Travel grants , Research Funding; Sanofi: Consultancy, Honoraria, Other: Travel grants , Research Funding; Gilead: Consultancy, Honoraria, Other: Travel grants , Research Funding; AbbVie: Consultancy, Honoraria, Other: Travel grants, Research Funding; Mundipharma: Consultancy, Honoraria, Other: Travel grants , Research Funding; Genzyme: Consultancy, Honoraria, Other: Travel grants , Research Funding; GSK: Consultancy, Honoraria, Other: Travel grants , Research Funding; Celgene: Consultancy, Honoraria, Other: Travel grants , Research Funding. Illerhaus:Riemser: Honoraria; Amgen: Honoraria.

Updated 12-year results of a randomized clinical trial comparing standard-dose to high-dose myeloablative chemotherapy in the adjuvant treatment of breast cancer with more than three positive nodes (LN+)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 549-549 ◽  
Author(s):  
A. M. Gianni ◽  
G. Bonadonna ◽  
G. Michelangelo
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Standard Dose ◽  
Survival Rates ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
Survival Advantage ◽  
High Dose ◽  
Free Survival ◽  
Intent To Treat

549 Aims: We conducted a multicenter randomized trial comparing sequential adjuvant standard-dose with high-dose chemotherapy in breast cancer patients younger than 60 years, with 4 or more positive nodes. Patients: Following surgery, patients were stratified by number of positive nodes (4–9 or 9), and randomly assigned to either conventional Epi–CMF (3 courses of epirubicin 120 mg/m2, followed by 6 courses of CMF), or high-dose chemotherapy (HDS) with stem cells support (one course of cyclophosphamide 7 g/m2, followed by one course of methotrexate 8 g/m2 with leukovorin rescue, by two courses of epirubicin 120 mg/m2, and by one course of thiotepa 600 mg/m2 plus melphalan 160–180 mg/m2 with stem cell autografting). Tamoxifen (20 mg/d × 5 yr) was also planned regardless of menopausal and receptor status. The study was designed with a power of 80% to detect a 15% increase in progression-free survival at 5 years in the HDS arm. Results: Of the initially enrolled 398 patients, 16 were ineligible, and the remaining 382 patients (Epi–CMF: 197 patients, HDS: 185 patients) were analyzed according to intent-to- treat. One patient treated with HDS (0.5%) died of interstitial pneumonia. With a median follow-up of 136 months, the 12-year progression-free survival rates were 44% and 52% for the Epi–CMF and the HDS groups, respectively, and the overall survival rates were 51% and 60%, respectively. However, among the 68 patients younger than 36 years, and the 189 patients with 4–9 LN+, those in the HDS group showed a trend for a progression-free survival advantage (HR 0.76 and 0.74, respectively). Conclusions: In the intent-to-treat analysis the 9% overall survival advantage associated with the HDS regimen failed to reach statistical significance in a study powered to detect a 15% difference. To reliably define the role of high-dose therapy, meta-analysis of patient data from all relevant randomized trials (such as that planned by the Early Breast Cancer Trialists’ Collaborative Group) is needed. Supported in part by AIRC and Pharmacia & Upjohn, Milano, Italy. No significant financial relationships to disclose.

High Dose Chemotherapy with Autologous Stem Cell Transplantation in Malignant Lymphoma - A Single Center Experience.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5483-5483
Author(s):  
Ulrich J.M. Mey ◽  
Vandana Jha ◽  
Marcus Gorschlueter ◽  
John W. Strehl ◽  
Tilman Sauerbruch ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Malignant Lymphoma ◽  
Autologous Stem Cell Transplantation ◽  
Median Overall Survival ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
First Line ◽  
Free Survival

Abstract Introduction High-dose chemotherapy with autologous stem cell transplantation plays an important role in the treatment of malignant lymphoma. Here, we report on a retrospective analysis of the data of 52 patients with malignant lymphoma who were consecutively treated with high-dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT) at the University Hospital of Bonn, Germany, between 1996 and 2004. Patients and methods A total of 52 consecutive patients were transplanted. Forty patients (76.9%) had aggressive non-Hodgkin’s lymphoma, 5 (9.6%) had indolent non-Hodgkin’s lymphoma, and 7 (13.5%) had Hodgkin’s disease. Thirty-two (61.5%) patients were treated with HDT and ASCT as first-line therapy. Of these, 15 patients received up-front chemotherapy due to the presence of &gt; 2 adverse prognostic factors according to the international prognostic index, 12 patients received high-dose chemotherapy due to incomplete response to standard induction chemotherapy and five patients were treated for primary refractory disease. Twenty (38.5%) patients had recurrent lymphoma. Chemosensitive relapse was present in 17 patients whereas three patients were treated for chemoresistant disease. The conditioning regimen was BEAM in 19 (36.5%), Mega-CHOEP in 16 (30.8%), CEIAP in 6 (11.5%), CEI in 5 (9.6%), and cyclophosphamide/ total body irradiation in 3 (5.8%) patients, respectively. Other regimens were used in 3 patients (5.7%). Results A complete remission was achieved in 35 of 52 patients (67.3%). At a median follow-up duration of 39.7 months (range 10–110), estimated 3-year overall survival was 55.8% and 3-year progression free survival was 47.8%. Median overall survival was 63.6 months, and median progression-free survival was 23.4 months. There were 6 (11.5%) deaths due to treatment-related toxicity within the first 50 days after transplantation. Five of these patients had relapsed disease and one had primary refractory disease. Median overall survival was 63.6 months in the primary high-risk group (n=15). Median overall survival in patients treated for incomplete response to first-line chemotherapy or chemosensitive relapse (n=12 and n=17, respectively) has not been reached yet; the mean overall survival in these subgroups was 67.7 and 57.2 months, respectively. Median overall survival was 5.5 months in the chemoresistant relapse group (n=3), and 6.8 months in the primary refractory group (n=5), respectively. Pre-transplantation disease status was the most important prognostic factor in determining overall survival and progression-free survival. Conclusions Our results confirm that HDT and ASCT is a highly effective therapy in patients with malignant lymphoma. Patients with primary high-risk disease, incomplete response to conventional first-line therapy or with sensitive relapse have a good prognosis, while primary refractory and patients with resistant relapse do not benefit from HDT with ASCT.

Treating relapsed and refractory metastatic germ cell tumours with high-dose chemotherapy with carboplatin and etoposide and autologous haematopoietic stem cell transplantation

2020 ◽  
pp. 107815522096454
Author(s):  
Ismail Erturk ◽  
Nuri Karadurmus ◽  
Halil Kızıloz ◽  
Ramazan Acar ◽  
Birol Yildiz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Data ◽  
Real Life ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
Haematopoietic Stem Cell ◽  
High Dose ◽  
Free Survival ◽  
Real Life Data ◽  
Single Centre Study

Introduction and aim To demonstrate the real-life data about patients who underwent AHSCT due to GCT. Methods Between November 2016 and April 2020, 64 patients who received CE as high-dose chemotherapy for AHSCT in the Gulhane Education and Research Hospital were included in the study. Sixty-one patients received one AHSCT with CE chemotherapy regimen. Survival data and clinical characteristics were evaluated retrospectively. Results The mean age of the patients were 31.9 ± 9 (min-max:18–55). With a median follow-up of 10.7 ± 8.7 months, the 1-year progression-free survival (PFS) rate was 57.8%, and the 1-year overall survival rate was 77.5%. Median overall survival (OS) and progression-free survival (PFS) times were 21.5 ± 1.8 (95% CI: 14.5–33.4) and 20 ± 2 months, respectively. The response rate was 72%. There were three treatment-related deaths. Conclusion This sizeable single-centre study shows that patients with relapsed metastatic GCT are curable by CE as high dose chemotherapy plus AHSCT with reliable toxicity even for a single cycle.

scholarly journals ETMR-14. TREATMENT OF EMBRYONAL TUMOURS WITH MULTILAYERED ROSETTES (ETMR) WITH CARBOPLATIN-ETOPOSIDE INDUCTION AND TANDEM HIGH-DOSE CHEMOTHERAPY WITHIN THE PROSPECTIVE HIT-TRIALS AND REGISTRIES

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii325-iii326
Author(s):  
Björn-Ole Juhnke ◽  
Marco Gessi ◽  
Nicolas Ulrich Gerber ◽  
Carsten Friedrich ◽  
Christine Haberler ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Disease Relapse ◽  
Total Resection ◽  
Free Survival ◽  
Entire Cohort ◽  
Innovative Therapies ◽  
Embryonal Tumours ◽  
Aggressive Tumors

Abstract BACKGROUND Embryonal tumours with multilayered rosettes (ETMR) are highly aggressive tumors, mostly occurring in infants. Published clinical data refer to retrospective cohorts of inhomogeneously treated patients. Here, we describe the outcome of patients, who were prospectively treated within the P-HIT2000-trial, the subsequent HIT2000-interim-registry and earlier HIT-trials. PATIENTS AND METHODS Nineteen patients from the P-HIT2000-trial (2001–2011), 12 patients from the subsequent HIT2000-interim-registry (2012–2014) and 4 patients from earlier HIT-trials with centrally reviewed neuropathological and molecularly-confirmed diagnosis of ETMR were included. Outcome of 18 patients treated with carboplatin-etoposide-induction followed by tandem-high-dose chemotherapy (“CARBO-ETO+HDCT”) with stage-stratified radiotherapy administered in case of persistant disease, relapse or progression were compared to patients treated with HIT-SKK chemotherapy ± radiotherapy (n=9) or other regimens (n=8). RESULTS Median age at diagnosis was 2.9(1.0–5.3) years. Metastases at diagnosis were detected in 9 patients (26%). For the entire cohort of n=35, 5-year overall survival (OS) was 26.7%, and progression-free survival (PFS) was 18.5%. Five-year OS for patients with CARBO-ETO+HDCT, SKK chemotherapy or other regimens was 44.4%, 13.0% and 0%, respectively (p=0.006). Five-year PFS was 33.3%, 0% and 0%, respectively (p=0.119). Of 10 survivors, n=8 were treated with CARBO-ETO+HDCT; n=4 had craniospinal, n=2 local and n=4 no radiotherapy. Impact of initial gross-total-resection (p=0.231) and non-metastatic disease (p=0.097) was limited. CONCLUSIONS We show improved survival with carboplatin-etoposide-induction followed by tandem-high-dose chemotherapy, indicating that a cure is possible for some patients. However, despite intensive treatment, outcome is unsatisfactory and innovative therapies urgently need to be included in an upfront setting.

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