PATH-32. EXTENT, PATTERN, AND PROGNOSTIC VALUE OF MGMT PROMOTOR METHYLATION: DOES IT DIFFER BETWEEN GLIOBLASTOMA AND IDH-WILDTYPE/TERT-MUTATED ASTROCYTOMA?

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi122-vi122
Author(s):  
Nico Teske ◽  
Philipp Karschnia ◽  
Jonathan Weller ◽  
Sebastian Siller ◽  
Mario M Dorostkar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Sanger Sequencing ◽  
Favourable Outcome ◽  
Who Grade ◽  
Cpg Sites ◽  
Specific Pcr ◽  
Grade Ii ◽  
Radio Chemotherapy ◽  
Who Grade Iii ◽  
Grade Iii

Abstract INTRODUCTION The cIMPACT-NOW update 6 introduced glioblastoma diagnosis based on the combination of IDH-wildtype (IDHwt) status and TERT promotor mutation (pTERTmut). In glioblastoma as defined by histopathology according to the WHO 2016 classification, MGMT promotor status is associated with outcome. Whether this is also true in glioblastoma defined by molecular markers is yet unclear. METHODS We searched the institutional database for patients with: 1.) glioblastoma defined by histopathology; and 2.) IDHwt astrocytoma with pTERTmut. MGMT promotor methylation was analysed using methylation-specific PCR and Sanger sequencing of CpG sites within the MGMT promotor region. RESULTS We identified 224 patients with glioblastoma diagnosed based on histopathology, and 71 patients with IDHwt astrocytoma with pTERTmut (32 astrocytomas WHO grade II and 39 astrocytomas WHO grade III). There was no difference in the number of MGMT methylated tumors between the two groups as determined per PCR, and also neither the number nor the pattern of methylated CpG sites differed as determined per Sanger sequencing. Progression-free (PFS) and overall survival (OS) was similar between the two groups. Surgery was associated with improved overall survival in IDHwt astrocytoma with pTERTmut. In patients treated with radiochemotherapy or radiotherapy, higher numbers of methylated CpG sites were associated with favourable outcome in both groups. CONCLUSION Extent and pattern of methylated CpG sites are similar in glioblastoma and IDHwt astrocytoma with pTERTmut. In both groups, higher numbers of methylated CpG sites are associated with favourable outcome when radio/chemotherapy is administered. Surgery may form the basis for favourable outcome.

scholarly journals Extent, pattern, and prognostic value of MGMT promotor methylation: does it differ between glioblastoma and IDH-wildtype/TERT-mutated astrocytoma?

2021 ◽  
Author(s):  
Nico Teske ◽  
Philipp Karschnia ◽  
Jonathan Weller ◽  
Sebastian Siller ◽  
Mario M. Dorostkar ◽  
...  
Keyword(s):  
Sanger Sequencing ◽  
Favourable Outcome ◽  
Outcome Evaluation ◽  
Who Grade ◽  
Cpg Sites ◽  
Specific Pcr ◽  
Grade Ii ◽  
Prospective Cohorts ◽  
Who Grade Iii ◽  
Grade Iii

Abstract Introduction The cIMPACT-NOW update 6 first introduced glioblastoma diagnosis based on the combination of IDH-wildtype (IDHwt) status and TERT promotor mutation (pTERTmut). In glioblastoma as defined by histopathology according to the WHO 2016 classification, MGMT promotor status is associated with outcome. Whether this is also true in glioblastoma defined by molecular markers is yet unclear. Methods We searched the institutional database for patients with: (1) glioblastoma defined by histopathology; and (2) IDHwt astrocytoma with pTERTmut. MGMT promotor methylation was analysed using methylation-specific PCR and Sanger sequencing of CpG sites within the MGMT promotor region. Results We identified 224 patients with glioblastoma diagnosed based on histopathology, and 54 patients with IDHwt astrocytoma with pTERTmut (19 astrocytomas WHO grade II and 38 astrocytomas WHO grade III). There was no difference in the number of MGMT methylated tumors between the two cohorts as determined per PCR, and also neither the number nor the pattern of methylated CpG sites differed as determined per Sanger sequencing. Progression-free (PFS) and overall survival (OS) was similar between the two cohorts when treated with radio- or chemotherapy. In both cohorts, higher numbers of methylated CpG sites were associated with favourable outcome. Conclusions Extent and pattern of methylated CpG sites are similar in glioblastoma and IDHwt astrocytoma with pTERTmut. In both tumor entities, higher numbers of methylated CpG sites appear associated with more favourable outcome. Evaluation in larger prospective cohorts is warranted.

scholarly journals A systematic review of treatment outcomes in pediatric patients with intracranial ependymomas

2013 ◽  
Vol 11 (6) ◽  
pp. 673-681 ◽  
Author(s):  
Tene A. Cage ◽  
Aaron J. Clark ◽  
Derick Aranda ◽  
Nalin Gupta ◽  
Peter P. Sun ◽  
...  
Keyword(s):  
Overall Survival ◽  
Pediatric Patients ◽  
Progression Free Survival ◽  
Tumor Location ◽  
Who Grade ◽  
Free Survival ◽  
Grade Ii ◽  
Infratentorial Tumors ◽  
Who Grade Iii ◽  
Grade Iii

Object Ependymoma is the third most common primary brain tumor in children. Tumors are classified according to the WHO pathological grading system. Prior studies have shown high levels of variability in patient outcomes within and across pathological grades. The authors reviewed the results from the published literature on intracranial ependymomas in children to describe clinical outcomes as they relate to treatment modality, associated mortality, and associated progression-free survival (PFS). Methods A search of English language peer-reviewed articles describing patients 18 years of age or younger with intracranial ependymomas yielded data on 182 patients. These patients had undergone treatment for ependymoma with 1 of 5 modalities: 1) gross-total resection (GTR), 2) GTR as well as external beam radiation therapy (EBRT), 3) subtotal resection (STR), 4) STR as well as EBRT, or 5) radiosurgery. Mortality and outcome data were analyzed for time to tumor progression in patients treated with 1 of these 5 treatment modalities. Results Of these 182 patients, 69% had supratentorial ependymomas and 31% presented with infratentorial lesions. Regardless of tumor location or pathological grade, STR was associated with the highest rates of mortality. In contrast, GTR was associated with the lowest rates of mortality, the best overall survival, and the longest PFS. Children with WHO Grade II ependymomas had lower mortality rates when treated more aggressively with GTR. However, patients with WHO Grade III tumors had slightly better survival outcomes after a less aggressive surgical debulking (STR+EBRT) when compared with GTR. Conclusions Mortality, PFS, and overall survival vary in pediatric patients with intracranial ependymomas. Pathological classification, tumor location, and method of treatment play a role in outcomes. In this study, GTR was associated with the best overall and PFS rates. Patients with WHO Grade II tumors had better overall survival after GTR+EBRT and better PFS after GTR alone. Patients with WHO Grade III tumors had better overall survival after STR+EBRT. Patients with infratentorial tumors had improved overall survival compared with those with supratentorial tumors. Progression-free survival was best in those patients with infratentorial tumors following STR+EBRT. Consideration of all of these factors is important when counseling families on treatment options.

scholarly journals The Expression of Progesterone Receptors in Meningiomas of Different Grades

2019 ◽  
Vol 8 (2) ◽  
pp. 65-69
Author(s):  
Mohammad Tahir ◽  
Tehreem Atif ◽  
Summaya Sohail ◽  
Arfa Nawazish ◽  
Huma Mushtaq
Keyword(s):  
Progesterone Receptor ◽  
Treatment Options ◽  
Progesterone Receptors ◽  
Lower Grade ◽  
Immunoperoxidase Method ◽  
Nuclear Staining ◽  
Who Grade ◽  
Grade Ii ◽  
Who Grade Iii ◽  
Grade Iii

Background: Meningiomas are slow growing intracranial and intraspinal neoplasms with a tendency to recur locally. WHO grades them as I (benign), II (atypical) and III (anaplastic) in order of their increasing aggressiveness, based on histological parameters and brain parenchymal invasion. Progesterone receptors (PR) are more prevalent amongst the lower grade meningiomas. The objective of this study was to determine the immunohistochemical expression of progesterone receptors in meningiomas of different grades.Material and Methods: A total of 100 cases were selected over a period of 2.5 years. Three to five microns’ thick sections stained with Hematoxylin and Eosin were examined microscopically by a team of two Histopathologists and graded into grades I, II and III, according to 2016 WHO classification criteria. Another section of the original tumor was stained with progesterone receptor antibody using the conventional immunoperoxidase method. Stained slides were than examined by the same team of Histopathologists and declared positive (if nuclear staining was observed in more than 10% of tumor cells) or negative. Statistical analysis was done using SPSS version 21.Results: Out of a total of 100 cases of meningioma, there were 79 cases of benign/typical WHO grade I, 15 cases of atypical/ WHO grade II and 6 cases of anaplastic/ WHO grade III tumor. PR status was positive in 89.8 % (71/79) of grade I meningiomas and 46.6 % (7/15) of grade II/Atypical meningiomas. The 06 cases of Anaplastic/WHO grade III tumors were negative for PR. There was a higher prevalence of Progesterone receptors in female patients (89.8%; 53/59) as compared to male meningioma patients (60.9%; 25/41).Conclusion: We observed a decreased expression of progesterone receptor in higher grades of meningioma in this study. It is an effort to explore conservative treatment options for inoperable lesions, as anti-progesterone therapy may hold a promise as a new treatment option in the near future.

The concept of the “Hexahedron” in the supratotal resection of the frontal gliomas: A technical note

2021 ◽  
Author(s):  
Pu Cai ◽  
Gang Bai ◽  
Jun Peng ◽  
Yun Li ◽  
Shanli Che ◽  
...  
Keyword(s):  
Tumour Volume ◽  
Extent Of Resection ◽  
Technical Note ◽  
Subtotal Resection ◽  
Diffuse Astrocytoma ◽  
Who Grade ◽  
Grade Ii ◽  
Supratotal Resection ◽  
Who Grade Iii ◽  
Grade Iii

Abstract OBJECTIVE To evaluate the value of the concept of the “Hexahedron” in the supratotal resection (SPTR) of frontal gliomas in both dominant and nondominant hemispheres . METHODS All consecutive patients who underwent SPTR for frontal gliomas under the guidance from the concept of the “Hexahedron” were retrospectively analysed for lesion location, pathology, extent of resection (EOR), and complications from May 2020 to June 2021. Volumetric EOR was measured and classified as SPTR, (in which the volume of the postoperative cavity was larger than the preoperative tumour volume), gross total resection (GTR, > 95% by volume) or subtotal resection (STR, ≤ 95% by volume) after independent radiological review. RESULTS Six men and two women (mean age: 47.13 years; range: 26–69 years) were included. All eight patients underwent frontal craniotomy combined frontotemporal craniotomy for resection of frontal gliomas. Neuropathological examination confirmed a diagnosis of glioblastoma WHO Grade IV in 4 patients, anaplastic oligodendroglioma WHO Grade III in 1, anaplastic astrocytoma WHO Grade III in 2 and diffuse astrocytoma WHO Grade II in 1. SPTR was achieved in six patients and STR was achieved in two. The main postoperative complications were contralateral paresis in 2 patients and memory disturbances in 1 patient. There were no cases of rebleeding or secondary operation during hospitalization. CONCLUSIONS In the presented eight cases the concept of the “Hexahedron” allowed for safe surgical supratotal resection of frontal gliomas.

scholarly journals PATH-28. EXTENT AND PROGNOSTIC VALUE OF MGMT PROMOTOR METHYLATION DEPEND ON IDH MUTATION AND 1p19q CO-DELETION IN GLIOMA WHO GRADE II

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii170-ii170
Author(s):  
Philipp Karschnia ◽  
Nico Teske ◽  
Sebastian Siller ◽  
Mario M Dorostkar ◽  
Jonathan Weller ◽  
...  
Keyword(s):  
Overall Survival ◽  
Dna Methyltransferase ◽  
Methylation Status ◽  
Malignant Progression ◽  
Wild Type ◽  
Who Grade ◽  
Cpg Sites ◽  
Idh Mutations ◽  
Promotor Region ◽  
Grade Ii

Abstract INTRODUCTION Methylation of the promotor region of the O6-methylguanin-DNA-methyltransferase (MGMT) gene is associated with increased survival in low- and high-grade glioma. It is unknown whether this association also applies to the 2016 WHO categories of glioma WHO grade II. MATERIAL AND METHODS We retrospectively searched the institutional database of the Center for Neuro-Oncology for patients with glioma WHO grade II. Patients were assigned to one of three groups according to the 2016 WHO classification system: 1. 1p19q co-deleted oligodendroglioma, IDH mutant; 2. 1p19q non-codeleted astrocytoma, IDH mutant; 3. 1p19q non-codeleted astrocytoma, IDH wild-type. MGMT methylation status was analysed using Sanger sequencing of the CpG sites 74-98 within the MGMT promotor region. The total number of methylated CpG sites was calculated for each patient. RESULTS 155 patients with glioma WHO grade II were encountered, including 81 1p19q co-deleted, IDH mutant oligodendrogliomas; 54 IDH mutant astrocytomas; and 20 IDH wild-type astrocytomas. The mean number of methylated CpG sites among oligodendrogliomas was significantly higher when compared to IDH mutant astrocytomas (18.9 ± 0.4 vs. 16.3 ± 0.6; p = 0.001). In turn, the number of methylated CpG sites among IDH mutant astrocytomas was higher when compared to IDH wild-type astrocytomas (16.3 ± 0.6 vs. 12.3 ± 1.9; p = 0.007). Median follow-up was estimated at 35 months. Median time to malignant progression was 87 months for all patients, and median overall survival was not reached. In the entire cohort, a larger number of methylated CpG sites was prognostic of overall survival and time to malignant progression. When analysed separately for the three WHO subgroups, a similar association was only retained in IDH wild-type astrocytoma. CONCLUSION In our series of WHO II gliomas, MGMT promotor methylation appeared strongly associated with 1p19q codeletion and IDH mutations. MGMT promotor methylation was only prognostic in IDH wild-type astrocytoma.

Lack of prognostic relevance of alterations in the epidermal growth factor receptor—transforming growth factor-α pathway in human astrocytic gliomas

1996 ◽  
Vol 85 (4) ◽  
pp. 634-641 ◽  
Author(s):  
Andreas Waha ◽  
Axel Baumann ◽  
Helmut K. Wolf ◽  
Rolf Fimmers ◽  
Jürgen Neumann ◽  
...  
Keyword(s):  
Growth Factor ◽  
Gene Amplification ◽  
Transforming Growth Factor ◽  
Growth Factor Receptor ◽  
Who Grade ◽  
Transforming Growth Factor Α ◽  
Grade Ii ◽  
Astrocytic Gliomas ◽  
Who Grade Iii ◽  
Grade Iii

✓ Alterations in the epidermal growth factor receptor (EGFR) and its main ligand, transforming growth factor-α (TGFα), were investigated for a possible prognostic relevance in 125 astrocytic gliomas (44 World Health Organization (WHO) Grade II, 19 WHO Grade III, and 62 WHO Grade IV tumors). The TGFα and EGFR proteins were detected immunohistochemically using monoclonal antibodies. A positive immunoreaction to TGFa was detected in 33 (75%) of 44 WHO Grade II astrocytomas, 18 (95%) of 19 WHO Grade III astrocytoma, and 50 (81%) of 62 WHO Grade IV glioblastomas. No correlation between TGFα immunoreaction and duration of survival could be found. A positive EGFR immunoreaction was detected in seven (16%) of 44 WHO Grade II astrocytomas, five (26%) of 19 WHO Grade III astrocytomas, and 32 (52%) of 62 WHO Grade IV glioblastomas. Of these gliomas, 97 (26 WHO Grade II, 17 WHO Grade III, and 54 WHO Grade IV gliomas) were examined for EGFR gene amplification using a differential polymerase chain reaction assay. Amplification of the EGFR gene was detected in none of the WHO Grade II astrocytomas, one (6%) of 17 WHO Grade III astrocytomas, and 18 (33%) of 54 WHO Grade IV glioblastomas. Twenty-two of the tumors investigated showed a positive EGFR immunoreaction without detectable gene amplification (five WHO Grade II, four WHO Grade III, and 13 WHO Grade IV tumors). Gene amplification was invariably associated with a positive EGFR immunoreaction. For the entire study group, a strong correlation between EGFR alterations (gene amplification and positive immunoreaction) and survival could be found. However, this correlation only reflected the higher percentages of cases with EGFR alterations in malignant gliomas and was not an independent prognostic factor as determined by multifactorial analysis. These data demonstrate that EGFR alterations are frequent events in astrocytic gliomas and are largely restricted to glioblastomas. However, within one tumor grade they do not provide prognostic information.

CBIO-18. TP53-MUTANT OLIGODENDROGLIOMA: A SINGLE INSTITUTION CASE SERIES

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi30-vi31
Author(s):  
Mason Webb ◽  
Sani Kizilbash ◽  
Thomas Kollmeyer ◽  
Robert Jenkins ◽  
Sarah Sung ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Tp53 Mutation ◽  
Case Series ◽  
Molecular Testing ◽  
Diffuse Glioma ◽  
Who Grade ◽  
Tp53 Mutations ◽  
Grade Ii ◽  
Who Grade Iii ◽  
Grade Iii

Abstract TP53 mutations are frequent in IDH-mutant astrocytomas but unusual in oligodendroglioma and the clinical significance of TP53 mutations in oligodendroglioma are not well characterized. We reviewed genetically defined oligodendroglioma (i.e., IDH-mutant, whole-arm 1p/19q-codeleted diffuse glioma) cases that were molecularly profiled (2017-2020) at our institution and identified 7 cases with TP53 mutation (9%; n=76). Molecular testing was performed using targeted neuro-oncology NGS panel (50-gene mutation and/or 187-gene mutation/rearrangement) and OncoScan™ microarray. Four (of 7) patients were female. Median age at diagnosis was 43 years (range, 23-63). Most common presenting symptom was seizures (3 of 7). All tumors were supratentorial. Histologically, 3 tumors were WHO grade II and 4 were WHO grade III. Two (of 3) patients with a WHO grade II tumor underwent biopsy and radiotherapy at diagnosis followed by temozolomide at recurrence (progression at 67 and 157 months after diagnosis; overall survival of 124 and 201 months). Three (of 4) patients with a WHO grade III tumor were diagnosed within the last two years and are currently progression-free after standard therapy. Molecularly, in addition to TP53 mutation(s), all cases had an IDH1 and TERT promoter mutation as well as other gene mutation(s) including FUBP1 (n=5), SETD2 (n=4), PIK3R1 (n=4), PIK3CA (n=3), NF1 (n=3) and CIC (n=3). In 3 (of 7) cases, the mutational profile with high mutation count enriched for C >T/G >A transitions was highly suggestive of a hypermutation phenotype (2 cases were recurrent tumors treated with temozolomide; a recurrent and a treatment-naïve tumor had mismatch repair gene mutation). Five (of 7) cases, including the 3 hypermutant cases, lacked functional TP53 (1 case with 2 mutations, 2 cases with 1 mutation plus loss of other copy, 2 cases with 1 mutation plus copy neutral loss-of-heterozygosity). TP53 mutations are uncommon in oligodendroglioma and appear enriched in hypermutant tumors.

P14.14 Adjuvant treatment versus initial observation in newly diagnosed WHO grade II and grade III oligodendroglioma: real-life data from two academic, tertiary care centers in Austria

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii40-ii41
Author(s):  
M J Mair ◽  
A Leibetseder ◽  
A Wöhrer ◽  
G Widhalm ◽  
K Dieckmann ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Adjuvant Therapy ◽  
Adjuvant Treatment ◽  
Tertiary Care ◽  
Newly Diagnosed ◽  
Who Grade ◽  
Initial Observation ◽  
Grade Ii ◽  
Radio Chemotherapy ◽  
Grade Iii

Abstract BACKGROUND Oligodendrogliomas are rare, slow-growing brain tumors with a survival prognosis of >10 years. Although adjuvant radio-chemotherapy has been shown to prolong survival, aggressive treatment comes at the cost of increased toxicity. Systematic data on the optimal timing of adjuvant treatment in oligodendroglioma are lacking. MATERIAL AND METHODS Patients treated for a newly diagnosed IDH-mutated, 1p/19q-codeleted oligodendroglioma (WHO grades II/III) in 2000 - 2018 at the Medical University of Vienna or the Kepler University Hospital Linz (Austria) were included in this retrospective study. Adjuvant treatment was defined as radiotherapy (RT), chemotherapy (CHT) or radio-chemotherapy (R-CHT) within 6 months after resection in the absence of progression. “Wait and see” was defined as regular follow up with magnetic resonance imaging and treatment at progression. RESULTS 185 patients were identified, comprising 123/185 (66.5%) WHO grade II and 62/185 (33.5%) WHO grade III oligodendrogliomas. Median age at diagnosis was 42 years (range: 20–82). Gross total resection (GTR) could be achieved in 77/178 (42.3%) evaluable patients. Adjuvant treatment was applied in 63/185 (38.2%) patients, of whom 43/63 (68.3%) underwent R-CHT, 9/63 (14.3%) CHT only and 11/63 (17.5%) RT only. 43/52 (82.7%) received temozolomide-based treatment, 1/52 (1.9%) procarbazine, lomustine and vincristine (PCV), 1/52 dacarbazine/fotemustine and in 7/52 (13.5%) patients, no data on used regimens was available. Adjuvant treatment was more frequently applied in WHO grade 3 tumors (p<0.001), while there was no association of adjuvant treatment with extent of resection (p=0.24). Patients after GTR who underwent adjuvant therapy presented with longer progression-free survival (PFS) compared to patients initially managed with observation (median: 150 months, 95%CI: 100 - not reached (n.r.) vs. median: 101 months, 95%CI: 73.2–115; p=0.053). In non-GTR tumors, patients with adjuvant therapy presented with a significantly longer median PFS of 107.5 months (95%CI: 62.8-n.r.) as compared to patients initially managed with observation (45.3 months, 95%CI: 41.2–78.8; p=0.025). CONCLUSION The application of adjuvant therapy was associated with favorable PFS in patients who underwent resection of newly diagnosed oligodendroglioma in this retrospective study. Prospective clinical trials should investigate the risks and benefits of adjuvant treatment versus initial observation in patients with oligodendroglioma.

The Newly Developed Modified BEACOPP-Regimen (BACOPP) Is Active and Feasible in Elderly Patients with Hodgkin Lymphoma: Results of a Phase II Study of the German Hodgkin Study Group (GHSG)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2600-2600
Author(s):  
Horst Mueller ◽  
Lucia Nogova ◽  
Dennis A Eichenauer ◽  
Teresa Halbsguth ◽  
Hiltrud Nisters-Backes ◽  
...  
Keyword(s):  
Overall Survival ◽  
Elderly Patients ◽  
Treatment Failure ◽  
Phase Ii Study ◽  
Final Analysis ◽  
Who Grade ◽  
Kaplan Meier ◽  
Advanced Stages ◽  
Who Grade Iii ◽  
Grade Iii

Abstract Background: Approximately 20% of patients diagnosed with Hodgkin lymphoma (HL) are more than 60 years of age. These elderly patients still have a poor prognosis, especially when presenting with advanced stages and higher age. The main reason is underdosing of treatment, which is due to reduced tolerability of chemotherapy and age-related comorbidities. In the GHSG experience, elderly patients in the HD9 trial did not profit from the BEACOPP regimen in terms of overall survival, though a better HL specific freedom from treatment failure was achieved as compared to COPP/ABVD. Thus, the GHSG has developed the BACOPP regimen (bleomycin, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), in which etoposide was omitted to improve tolerability. Further modifications were a 1 week pretreatment phase with vincristine and prednisone, a limitation of vincristine in patients older than 65 years, an increase of the anthracyclines dose, and concomitant application of erythropoietin. Here we report on the final analysis of this multi-center phase II study for elderly patients. Methods: Between 2004 and 2005, 65 patients with HL in intermediate or advanced stages aged between 60 and 75 years were recruited. Treatment consisted of 6 cycles BACOPP in patients achieving a complete remission (CR) after 4 cycles or 8 cycles BACOPP in case of PR (partial remission) after 4 cycles. The primary endpoints were protocol adherence and response rates. Secondary endpoints included WHO grade III/IV toxicities, Kaplan Meier estimates of progression free survival (PFS), freedom from treatment failure (FFTF), and overall survival (OS). Results: Sixty patients (92%) were eligible for the final analysis. The majority of treatment courses (75%) were administered according to protocol. However, there was a tendency towards reduced dosing in cycles 5 to 8, especially for patients who had reached a CR after 4 cycles of BACOPP. In total, 51 patients showed CR/CRu (85%), 2 PR (3%) and 4 progression of disease (7%). Survival estimates and their 95% confidence intervals are shown in table 1. Table 1. Kaplan-Meier rates and 95% confidence intervals (CI) for FFTF, PFS and OS. time point rate (%) CI (95%) FFTF 12 months 73 61–84 24 months 67 55–79 PFS 12 months 75 64–86 24 months 68 56–80 OS 12 months 85 76–94 24 months 76 65–87 WHO grade III–IV toxicities were documented in 52 patients (87%). With a median observation time of 33 months, 18 deaths (30%) have been observed. Seven therapy associated fatal outcomes were documented. Conclusion: The new BACOPP regimen developed for elderly HL patients shows a high CR rate (85%). The FFTF rate at 2 years is within the range known from other schedules in this patient cohort. Overall, the regimen is feasible, but the therapy-associated death rate was high in our patient cohort. Thus, further studies and new approaches are still needed to substantially improve the outcome of elderly patients with early unfavorable or advanced stage HL.

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