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Agnieszka Korfel,
Thomas Elter,
Eckhard Thiel,
Mathias Hänel,
Robert Möhle,
Roland Schroers,
Marcel Reiser,
Martin Dreyling,
Jan Eucker,
Christian W Scholz,
Bernd Metzner,
Alexander Röth,
Josef Birkmann,
Uwe Schlegel, Peter Martus,
Gerald Illerhaus,
Lars Fischer
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ABSTRACT: Background. The prognosis of patients with central nervous system relapse of aggressive lymphoma is very poor with no therapy established thus far. In a prospective multicenter phase II study we evaluated a potentially curative chemotherapy-only regimen in these patients. Design and Methods. Adult immunocompetent patients ≤65 years received induction chemotherapy with MTX/IFO/DEP (methotrexate 4 g/m2 i.v. day1, ifosfamide 2 g/m2 i.v. day3-5 and liposomal cytarabine 50mg intrathecally day6) and AraC/TT/DEP (cytarabine 3g/m2 i.v. day1-2, thiotepa 40 mg/m2 i.v. day2 and i.th. liposomal cytarabine 50mg intrathecally day3) followed by high-dose chemotherapy with carmustine 400 mg/m2 i.v. day -5, thiotepa 2x5mg/kg i.v. day -4 to -3 and etoposide 150 mg/m2 i.v. day -5 to -3 and autologous stem cell transplantation day0 (HD-ASCT). Results. Thirty eligible patients (median age 58 years) were enrolled. After HD-ASCT (n=24) there was a complete remission in 15 (63%), partial remission in two (8%) and progressive disease in seven (29%) patients. Myelotoxicity was the most adverse event with CTC grade 3/4 infections in 12% of MTX/IFO/DEP courses, 21% of AraC/TT/DEP courses and 46% of HD-ASCT courses. The 2-year time to treatment failure was 49%+/-19 for all patients and 58%+/-22 for patients completing HD-ASCT. Conclusions. The protocol assessed proved feasible and highly active with long-lasting remissions in a large proportion of patients. (ClinicalTrials.govIdentifier NCT01148173).
Haematologica 12/2012; · 6.42 Impact Factor
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ABSTRACT: The standard of care for primary central nervous system lymphoma (PCNSL) is systemic chemotherapy with or without whole brain radiotherapy or intrathecal chemotherapy. In contrast to treatment for other brain tumors, efforts at resection are discouraged. This is a secondary analysis of the German PCNSL Study Group-1 trial, a large randomized phase III study comprising 526 patients with PCNSL. Progression-free survival (hazard ratio [HR]: 1.39; 95% confidence interval [CI]: 1.10-1.74; P = .005) and overall survival (HR: 1.33; 95% CI: 1.04-1.70; P = .024) were significantly shorter in biopsied patients compared with patients with subtotal or gross total resections. This difference in outcome was not due to age or Karnofsky performance status (KPS). When controlled for the number of lesions, the HR of biopsy versus subtotal or gross total resection remained unchanged for progression-free survival (HR = 1.37; P = .009) but was smaller for overall survival (HR = 1.27; P = .085). This analysis of the largest PCNSL trial ever performed challenges the traditional view that the extent of resection has no prognostic impact on this disease. Therefore, we propose to reconsider the statement that efforts at resection should be discouraged, at least if resection seems safe, as is often the case in treatment of single PCNSL lesions.
Neuro-Oncology 09/2012; · 5.72 Impact Factor
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Patrick Roth, Peter Martus,
Philipp Kiewe,
Robert Möhle,
Hermann Klasen,
Michael Rauch,
Alexander Röth,
Stephan Kaun,
Eckhard Thiel,
Agnieszka Korfel,
Michael Weller
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ABSTRACT: To assess the outcome of elderly patients with primary CNS lymphoma (PCNSL) treated within the G-PCNSL-SG-1 trial.
We reviewed response, toxicity, and survival of patients with PCNSL aged 70 or more enrolled in the G-PCNSL-SG-1 trial.
A total of 126 of the 526 eligible patients (24%) and 66 of 318 patients (21%) in the per protocol population were aged 70 or more. Among all eligible patients, the rate of complete and partial responses (CR+PR) to HD-MTX-based chemotherapy was 44% in the elderly vs 57% in the younger patients (p = 0.016). Toxicity was age-independent except for a higher rate of grade III/IV leukopenia in the elderly (34% vs 21%, p = 0.007). Death on therapy was more frequent (18% vs 11%; p = 0.027), and progression-free survival (PFS) (4.0 vs 7.7 months, p = 0.014) and overall survival (12.5 vs 26.2 months, p < 0.001) inferior, in the elderly. A striking difference between younger and elderly patients was the PFS of CR patients of 35.0 in the younger vs 16.1 in the elderly patients (p = 0.024). Elderly patients were treated less often and less aggressively at salvage. However, age was not associated with survival from salvage whole brain radiotherapy in patients progressing during primary HD-MTX-based chemotherapy (p = 0.633).
Lower response rate and higher mortality on HD-MTX-based chemotherapy as well as lower PFS of CR patients and less salvage therapy contribute to the poor prognosis of elderly patients with PCNSL.
Neurology 08/2012; 79(9):890-6. · 8.31 Impact Factor
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Sandra Schwarzlose-Schwarck,
Christian W Scholz,
Anne C Regierer, Peter Martus,
Christian Neumann,
Piet Habbel,
Hongyu Liu,
Chuanbing Zang,
Jan-Hendrik Schefe,
Carsten-Oliver Schulz,
Kurt Possinger,
Jan Eucker
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ABSTRACT: Despite advances in the the first- and second-line treatment of metastatic breast cancer, there remains a large unmet need for additional treatment options. As preclinical studies have suggested that combining everolimus with carboplatin may produce higher activity than each drug by itself, we initiated a phase I study of this combination.
Patients with pre-treated metastatic breast cancer received weekly carboplatin at AUC2 and daily oral everolimus at different dose-levels (level I: 2.5 mg; II: 5 mg; III: 7.5 mg; IV: 10 mg). Three patients were assigned to dose-levels I to III, and six to dose-level IV. The primary end-point was to determine the maximum tolerated dose (MTD).
Fifteen patients were recruited to the study. The median number of previous chemotherapies was four (range: 1-11). No dose-limiting toxicity occurred at levels I-III during the first cycle. Based on the pre-determined definition, the maximum planned dose-level IV was selected as the MTD. Patients received a median of four cycles of treatment (range 1-13). Most frequent grade 3 and 4 toxicities included leukopenia, thrombocytopenia and infection. Response rates were as follows: 21% partial response, 43% stable disease, and 36% progressive disease.
Carboplatin and everolimus is a well-tolerated combination for heavily pre-treated metastatic breast cancer. Everolimus (10 mg/d) and carboplatin (AUC2 weekly) were defined as the MTD. This dose is currently being employed in an ongoing phase II trial.
Anticancer research 08/2012; 32(8):3435-41. · 1.73 Impact Factor
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ABSTRACT: Primary CNS lymphoma (PCNSL), a rare variant of extranodal non-Hodgkin's lymphoma, may cause various neurological symptoms and signs. The best therapeutic strategy is still a matter of debate. High-dose methotrexate (HD-MTX) is the most active compound and should be used as the backbone for any chemotherapy applied. Several other chemotherapeutic drugs have been assessed in combination with HD-MTX, but no standard has yet been defined. Whole-brain radiotherapy is active against PCNSL, but typically does not confer long-lasting remission and is associated with significant neurotoxicity in many patients. The recently published G-PCNSL-SG1 trial has shown that consolidating whole-brain radiotherapy after HD-MTX-based chemotherapy does not prolong overall survival and may therefore be deferred. Combined systemic and intraventricular polychemotherapy, or high-dose chemotherapy followed by stem cell transplantation may offer cures to younger patients. Improving treatment regimens without adding significant (neuro-)toxicity should be the focus of ongoing and future studies.
Expert Review of Anti-infective Therapy 05/2012; 12(5):623-33. · 2.65 Impact Factor
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The lancet oncology 02/2011; 12(2):119-120. · 14.47 Impact Factor
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Eckhard Thiel,
Agnieszka Korfel, Peter Martus,
Lothar Kanz,
Frank Griesinger,
Michael Rauch,
Alexander Röth,
Bernd Hertenstein,
Theda von Toll,
Thomas Hundsberger, [......],
Malte Leithäuser,
Tobias Birnbaum,
Lars Fischer,
Kristoph Jahnke,
Ulrich Herrlinger,
Ludwig Plasswilm,
Thomas Nägele,
Torsten Pietsch,
Michael Bamberg,
Michael Weller
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ABSTRACT: High-dose methotrexate is the standard of care for patients with newly diagnosed primary CNS lymphoma. The role of whole brain radiotherapy is controversial because delayed neurotoxicity limits its acceptance as a standard of care. We aimed to investigate whether first-line chemotherapy based on high-dose methotrexate was non-inferior to the same chemotherapy regimen followed by whole brain radiotherapy for overall survival.
Immunocompetent patients with newly diagnosed primary CNS lymphoma were enrolled from 75 centres and treated between May, 2000, and May, 2009. Patients were allocated by computer-generated block randomisation to receive first-line chemotherapy based on high-dose methotrexate with or without subsequent whole brain radiotherapy, with stratification by age (<60 vs ≥60 years) and institution (Berlin vs Tübingen vs all other sites). The biostatistics centre assigned patients to treatment groups and informed local centres by fax; physicians and patients were not masked to treatment group after assignment. Patients enrolled between May, 2000, and August, 2006, received high-dose methotrexate (4 g/m(2)) on day 1 of six 14-day cycles; thereafter, patients received high-dose methotrexate plus ifosfamide (1·5 g/m(2)) on days 3-5 of six 14-day cycles. In those assigned to receive first-line chemotherapy followed by radiotherapy, whole brain radiotherapy was given to a total dose of 45 Gy, in 30 fractions of 1·5 Gy given daily on weekdays. Patients allocated to first-line chemotherapy without whole brain radiotherapy who had not achieved complete response were given high-dose cytarabine. The primary endpoint was overall survival, and analysis was per protocol. Our hypothesis was that the omission of whole brain radiotherapy does not compromise overall survival, with a non-inferiority margin of 0·9. This trial is registered with ClinicalTrials.gov, number NCT00153530.
551 patients (median age 63 years, IQR 55-69) were enrolled and randomised, of whom 318 were treated per protocol. In the per-protocol population, median overall survival was 32·4 months (95% CI 25·8-39·0) in patients receiving whole brain radiotherapy (n=154), and 37·1 months (27·5-46·7) in those not receiving whole brain radiotherapy (n=164), hazard ratio 1·06 (95% CI 0·80-1·40; p=0·71). Thus our primary hypothesis was not proven. Median progression-free survival was 18·3 months (95% CI 11·6-25·0) in patients receiving whole brain radiotherapy, and 11·9 months (7·3-16·5; p=0·14) in those not receiving whole brain radiotherapy. Treatment-related neurotoxicity in patients with sustained complete response was more common in patients receiving whole brain radiotherapy (22/45, 49% by clinical assessment; 35/49, 71% by neuroradiology) than in those who did not (9/34, 26%; 16/35, 46%).
No significant difference in overall survival was recorded when whole brain radiotherapy was omitted from first-line chemotherapy in patients with newly diagnosed primary CNS lymphoma, but our primary hypothesis was not proven. The progression-free survival benefit afforded by whole brain radiotherapy has to be weighed against the increased risk of neurotoxicity in long-term survivors.
The lancet oncology 10/2010; 11(11):1036-47. · 14.47 Impact Factor
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ABSTRACT: The frequency of meningeal dissemination (MD) in primary CNS lymphoma (PCNSL), its prognostic impact, and optimal management have not been defined thus far. In 69 of 92 (75%) immunocompetent patients, primarily diagnosed with PCNSL at our institution between January 1994 and February 2007, cerebrospinal fluid was analyzed for MD. MD was found by cytomorphology in 7/63 (11%), by immunophenotyping in 1/32 (3%), and by PCR of the IgH CDR III region in 6/37 (16%). Neuroradiologic examination revealed MD in 3 of 69 patients (4%). Median event-free survival (EFS) of patients with MD diagnosed by any of the methods was 26 months, of those without MD 34.1 months (P = .24); median overall survival (OAS) of these two patients' groups was 45.5 and 42.5 months, respectively (P = .34). Patients with cytomorphologic proof of MD had a median EFS of 15.4 months and OAS of 18.5 months, those without MD 34.3 and 45 months (P = .018 and .017, respectively). We found a low frequency of MD despite the use of putatively sensitive diagnostic methods. No impact on outcome was seen for MD, diagnosed by any of the methods used; however, patients with cytomorphologic proof of MD had a significantly shorter median EFS and OAS.
Neuro-Oncology 04/2010; 12(4):409-17. · 5.72 Impact Factor
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ABSTRACT: This retrospective, single-center study assessed the feasibility, outcome, and late side effects of the treatment of immunocompetent patients with primary central nervous system lymphoma (PCNSL) at the authors' institution.
All 72 consecutive patients diagnosed with PCNSL between January 1994 and February 2005 were scheduled to receive high-dose methotrexate (HDMTX)-based chemotherapy.
The median age of the patients was 62 years and the median Karnofsky performance score (KPS) was 70. Twelve patients did not receive HDMTX-based chemotherapy because of poor physical condition or renal insufficiency. Of the 60 patients treated with HDMTX-based chemotherapy, the treatment of 9 was followed with whole-brain irradiation. Of 54 patients who were evaluable for response, 35 (65%) responded (52% with a complete response and 13% with a partial response), and 19 patients (35%) did not. At a median follow-up of 58.7 months, the median progression-free survival was 9 months and the median overall survival (OAS) was 41.4 months. According to the Memorial Sloan-Kettering Cancer Center (MSKCC) prognosis score, patients could be divided into 3 groups with significantly different OAS: 52.9 months for patients aged <50 years, 42.4 months for patients aged >or= 50 years and with a KPS >70, and 5.2 months for patients aged >or= 50 years and with a KPS <70 (P= .009, log-rank test).
Promising long-term results could be achieved with HDMTX-based chemotherapy in patients with PCNSL in this monocenter study. The MSKCC score proved useful for predicting survival.
Cancer 05/2008; 112(8):1812-20. · 4.77 Impact Factor
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ABSTRACT: Leucovorin and extracorporeal removal of methotrexate (MTX) have limited efficacy in delayed MTX elimination after high-dose methotrexate (HD-MTX) therapy. Glucarpidase (carboxypeptidase G2) cleaves MTX into nontoxic metabolites, but experience with this enzyme is limited in adult patients. We evaluated the effects of glucarpidase intervention in adult and elderly patients with delayed MTX elimination.
Forty-three patients (age, 18-78 years) with MTX serum concentrations (sMTX) of 1-1,187 micromol/l received glucarpidase, leucovorin rescue guided by MTX immunoassay, and standard supportive care. MTX and MTX metabolites were quantified in serum (24 patients) and urine (8 patients) by high-performance liquid chromatography. Contributory risk factors, toxicities, and survival were recorded in all patients.
Glucarpidase was well tolerated and resulted in an immediate >97% reduction in sMTX, with a 0.2%-35% urinary recovery of the total MTX dose as inactive MTX metabolites. Forty (93%) of 43 patients had normalization (n = 25) or improvement (n = 15) of their serum creatinine. Frequent grade III-IV MTX toxicities were hematological (60%) and mucositis (35%); only eight (19%) patients developed grade III-IV nephrotoxicity. Ten (23%) of 43 patients experienced fatal complications associated with HD-MTX therapy. Patients with three or more contributory risk factors for delayed MTX elimination had a significantly poorer survival than patients with fewer than three risk factors (hazard ratio, 3.64; confidence interval, 1.14-17.54).
Glucarpidase is well tolerated and produces a rapid inactivation of substantial amounts of MTX. However, overall results are still unsatisfactory in adult and elderly patients, suggesting that earlier recognition of delayed MTX elimination and more rapid intervention are needed.
The Oncologist 11/2007; 12(11):1299-308. · 3.91 Impact Factor
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ABSTRACT: Expression of the genes ERG (v-ets erythroblastosis virus E26 oncogene homolog) and BAALC (brain and acute leukemia, cytoplasmic) shows similarity during hematopoietic maturation and predicts outcome in acute myeloid leukemia. We hypothesized that like ERG, BAALC expression might be of prognostic significance in acute T-lymphoblastic leukemia (T-ALL) and that ERG and BAALC expression together would better identify the patient's risk profile.
ERG and BAALC mRNA expression were determined by real-time reverse transcriptase polymerase chain reaction in 153 adults with T-ALL. Patients were designated low or high ERG expressers and low or high BAALC expressers.
High BAALC expression correlated with a higher frequency of early T-ALL (P < .0001), CD34 positivity (P < .0001), coexpression of myeloid markers (P = .0001), and high ERG expression (P = .03). High BAALC compared with low BAALC patients had an inferior relapse-free survival (RFS; P = .0008) and overall survival (OS; P = .0001). In contrast, patients with low expression of both ERG and BAALC (representing 41% of all T-ALL patients) had the most favorable outcome (P < .0001; 4-year RFS: low ERG/low BAALC 81%; P < .0001; 4-year OS: low ERG/low BAALC 69%). On multivariable analysis, low ERG/low BAALC expression was of independent favorable prognostic significance (RFS, P = .001; OS, P = .003).
Low expression of both ERG and BAALC identifies T-ALL patients with a distinctly favorable long-term outcome.
Journal of Clinical Oncology 09/2007; 25(24):3739-45. · 18.37 Impact Factor
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ABSTRACT: Data on relapsed primary central nervous system lymphoma (PCNSL) are limited. We have evaluated the clinical characteristics and outcome of relapsed PCNSL patients from two German trials. Patients with relapsed disease after primary treatment were studied. Primary therapy consisted of high-dose methotrexate-based chemotherapy in all patients. Treatment for relapse was not predetermined. After a median follow-up of 22.5 months, 52 (36%) patients with relapse were identified among 143 patients with complete remission (CR) after primary treatment. The median disease-free survival was 10.25 (3-47.5) months. The median age at relapse was 59 years. Forty-four of 51 evaluable patients relapsed within the CNS, 6 systemically and one both cerebrally and systemically. The median survival time after first relapse was 4.5 (0.5-40.5) months. Karnofsky performance status (KPS) at relapse (P = 0.004), site of relapse (isolated systemic versus other, P = 0.049) and treatment for relapse (versus no treatment, P = 0.001) were independent prognostic factors for survival after relapse in multivariate analysis. Survival of patients with relapsed PCNSL is poor despite high response rates to salvage therapy. Good KPS, isolated systemic relapse and treatment for relapse were significantly associated with longer survival.
Journal of Neuro-Oncology 12/2006; 80(2):159-65. · 3.21 Impact Factor
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ABSTRACT: In adult T-lymphoblastic leukemia (T-ALL) disease-free survival remains limited to 32% to 46%. The adverse prognosis in T-ALL has not been attributed to cytogenetic or molecular aberrations. We have determined the prognostic impact of the oncogenic transcription factor ERG in T-ALL.
ERG expression was analyzed by real-time polymerase chain reaction (PCR) in 105 adults with newly diagnosed T-ALL treated on the German ALL protocols. Patients were dichotomized at ERG's median expression into low (n = 52) and high (n = 53) expressers. Homeobox (HOX) 11 and HOX11L2 expression was determined by real-time PCR.
High ERG expressers compared with low ERG expressers had an inferior overall survival (OS, P = .02; 5-year OS: high ERG 26% v low ERG 58%) and relapse-free survival (RFS, P = .003; 5-year RFS: high ERG 34% v low ERG 72%). On multivariable analysis high ERG expression (P = .005), immunophenotypic subgroups (early v mature v thymic T-ALL; overall P = .04), HOX11L2 positivity (P = .055), and absence of HOX11 (P = .017) were independent adverse risk factors predicting RFS. Patients with high ERG expression had a hazard ratio (HR) for relapse of 3.2. Within the good prognostic subgroup of thymic T-ALL (n = 57), high ERG (HR, 4.1; P = .02) and presence of HOX11L2 (HR, 6.6; P = .008) were independent adverse factors for RFS.
High expression of ERG is an adverse risk factor in adult T-ALL. Within thymic T-ALL, otherwise classified as standard-risk, high ERG expression-identified patients that were four times more likely to fail long-term RFS. The prognostic impact of ERG may assist treatment stratification and suggest the need of alternative regimens.
Journal of Clinical Oncology 11/2006; 24(29):4714-20. · 18.37 Impact Factor
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Kristoph Jahnke,
Agnieszka Korfel,
Brian Patrick O'Neill,
Jean-Yves Blay,
Lauren E Abrey, Peter Martus,
Philip M P Poortmans,
Tamara N Shenkier,
Tracy T Batchelor,
Edward A Neuwelt,
Jeffrey J Raizer,
David Schiff,
Hendrik Pels,
Ulrich Herrlinger,
Harald Stein,
Eckhard Thiel
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ABSTRACT: The aim of this study was to characterize the clinical presentation, course, and outcome of low-grade primary central nervous system lymphoma.
Cases were assessed in a retrospective series collected from 18 cancer centers in 5 countries.
Forty patients (18 men, 22 women; median age, 60 years [range, 19-78]) were identified. Involvement of a cerebral hemisphere or deeper brain structures was seen in 37 patients, only leptomeningeal involvement in 2 patients, and spinal cord disease in 1 patient. Chemotherapy/radiotherapy was conducted in 15 patients, radiotherapy alone in 12, chemotherapy alone in 10, and tumor resection alone in 2, whereas 1 patient received no treatment. The median progression-free, disease-specific, and overall survival were 61.5 (range, 0-204), 130 (range, 1-204), and 79 (range, 1-204) months, respectively. Only age 60 years or older was associated with shorter progression-free (p = 0.009), disease-specific (p = 0.015), and overall survival (p = 0.001) in multivariate analysis.
Low-grade primary central nervous system lymphoma differs from the high-grade subtype in its pathological, clinical, and radiological features. It has a better long-term outcome than primary central nervous system lymphoma in general with age 60 years or older adversely affecting survival.
Annals of Neurology 06/2006; 59(5):755-62. · 11.09 Impact Factor
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ABSTRACT: Monitoring cellular immune responses is one prerequisite for rational development of cancer vaccines. The primary objective of immune monitoring is to determine the efficacy of a vaccine to induce or augment a specific T-cell response. Further questions relate to the prevalence and functional relevance of spontaneous tumor-directed immune responses, the functional characteristics of T-cell responses, and, finally and most importantly, the relationship between immune monitoring assay results and clinical end points. The issue of T-cell monitoring has become more complex as different types and generations of assays have been adopted during the past decade and both standardization and validation of assays have often been insufficient. Because the development of assays parallel the clinical development of cancer vaccines, technical advances have been achieved simultaneously with broadening understanding of cancer immunity. Suitable animal models for immune monitoring are, however, lacking, because preclinical vaccine development in rodents does not allow serial immune monitoring of the peripheral blood, as is commonly used in patients. The current situation is characterized by a lack of universal standards for T-cell assessment, uncertainty about the association between immune monitoring assay results and clinical antitumor end points, and lack of knowledge regarding the contribution of different aspects of T-cell function to clinical efficacy. It is acknowledged that T-cell monitoring will have to be validated in large trials with clinically effective vaccines, but this necessity should not discourage the current application of novel assays within clinical trials of all stages.
Clinical Cancer Research 05/2006; 12(7 Pt 2):2346s-2352s. · 7.74 Impact Factor
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ABSTRACT: The exact rate of lymphomatous meningitis in primary central nervous system lymphomas (PCNSL) is uncertain. In this prospective multicenter study, cerebrospinal fluid (CSF) from 116 immunocompetent patients with newly diagnosed PCNSL was evaluated. Lymphoma cells were found in 18.1%, protein elevation (>45 mg/dL) in 65%, and CSF pleocytosis (>5/microL) in 36% of patients. Pleocytosis correlated with positive cytology, whereas CSF protein did not (specificity cell count vs. protein 74% vs. 34% [p<0.001], sensitivity 86% vs. 62% [p=0.18]).
Haematologica 04/2006; 91(3):429-30. · 6.42 Impact Factor
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ABSTRACT: The aim of this retrospective single-center study was to analyze the clinical characteristics and outcome of non-Hodgkin lymphoma (NHL) patients with central nervous system (CNS) involvement and to identify prognostic factors for survival. We searched our hospital records for NHL patients diagnosed with CNS involvement from 1982 to 2004, and 43 patients were identified. The median age was 63 years (range 23-88) and the median Karnofsky performance status was 55% (range 10-90). Treatment of CNS lymphoma included intrathecal chemotherapy in 33 patients (77%), systemic chemotherapy in 25 (58%), and radiotherapy in 16 (37%). Twenty-six patients showed a CNS response. The median survival after CNS manifestation was 5 months (range 2 days-82.5+months). Nine patients achieved long-term survival. Low lactate dehydrogenase (LDH) at CNS manifestation and a CNS response to therapy were favorable independent prognostic factors for survival in multivariate analysis (p = 0.051 and p < 0.0005, respectively), whereas a young age at initial diagnosis, initial CNS involvement, an initially normal LDH, and high-dose chemotherapy for CNS involvement were significant in univariate analysis. In conclusion, long-term survival can be achieved in patients with secondary CNS lymphoma. LDH at CNS manifestation and a CNS response to therapy were significantly associated with survival.
Annals of Hematology 01/2006; 85(1):45-50. · 2.62 Impact Factor
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Agnieszka Korfel, Peter Martus,
Mohammad R Nowrousian,
Dieter K Hossfeld,
Heinz Kirchen,
Joachim Brücher,
Matthias Stelljes,
Josef Birkmann,
Christian Peschel,
Rita Pasold,
Lars Fischer,
Kristoph Jahnke,
Eckhard Thiel
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ABSTRACT: The majority of the available data on primary central nervous system lymphoma (PCNSL) derive from small unicentric or oligocentric studies. In this multicentre study, we evaluated the response, survival and toxicity in PCNSL patients after carmustine, methotrexate 1.5 g/m2, procarbazine and dexamethasone (BMPD) chemotherapy and searched for prognostic factors. Fifty-six patients received the BMPD protocol (dexamethasone was given only in course 1). The overall complete response rate to chemotherapy was 61% (34/56). Ten complete responders received whole-brain irradiation and 24 were not irradiated. Responders to chemotherapy had significantly longer median overall survival than non-responders (18.2 vs. 9.9 months, P = 0.02). Median survival was significantly longer at institutions accruing at least four patients than at those with fewer patients (31.5 vs. 9.5 months, P = 0.03).
British Journal of Haematology 02/2005; 128(2):177-83. · 4.94 Impact Factor
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ABSTRACT: Adjuvant treatment strategies in uveal melanoma require determination of prognostic factors. Patients, who received primary therapy in 1994 and 1995 at our institution, were analysed. Of 271 patients 85% and 71% were available for follow up of 4 and 5 years. Forty three patients (15.9%) developed metastases. Kaplan-Meier analysis revealed a 5-year progression free survival (PFS) of 79% for the whole patient cohort. Extraocular tumor growth (EOG), ciliary body involvement or a largest tumor diameter (LTD) >14 mm were associated with a significantly lower 5-year PFS of 28%, 61.4% or 67.6%. In multivariate analysis time to progression was significantly associated with ciliary body involvement and LTD, and survival was associated with ciliary body involvement. Ciliary body involvement profoundly increased the risk for metastases (hazard ratio 6.9, P<0.001) within the first 3 years. This study determined patients with ciliary body involvement to be candidates for future adjuvant therapeutic interventions.
European Journal of Cancer 11/2004; 40(16):2389-95. · 5.54 Impact Factor
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Stefan Höcht,
Nikolaos E Bechrakis,
Martin Nausner,
Klaus-Martin Kreusel,
Heinz Kluge,
Jürgen Heese,
Jens Heufelder,
Dino Cordini,
Heinz Homeyer,
Hermann Fuchs, Peter Martus,
Michael H Foerster,
Thomas Wiegel,
Wolfgang Hinkelbein
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ABSTRACT: In June 1998, proton-beam therapy of ocular tumors started at the Hahn-Meitner Institute Berlin, Germany. The purpose of the present study is to evaluate treatment outcome for uveal melanomas.
245 consecutive patients with primary melanoma of the uvea were treated from June 1998 to April 2003 with a 68-MeV proton beam. In 96.2% of all patients, a uniform fractionation scheme was applied: single dose 15 CGE (cobalt gray equivalent), total dose 60 CGE on 4 consecutive days. Follow-up is available in 229 patients.
At the time of median follow-up (18.4 months), local control is 96.4% and 95.5% at 3 years. Eye retention rate is 92.6% at 20 months (median follow-up) and 87.5% at 3 years.
Proton-beam irradiation of uveal melanomas at the Hahn-Meitner Institute after the first 5 years of its initiation reveals local tumor control and eye retention rates in the range of other centers with larger experience. Delivering high treatment quality in hadron therapy from the beginning has been achieved.
Strahlentherapie und Onkologie 08/2004; 180(7):419-24. · 3.56 Impact Factor
