Search

Background: Androgen receptor (AR) expression is a potential therapeutic target in breast cancer (BC) as it is frequently expressed in the luminal A and B subtypes and in approximately one third of basal-like cancers. As AR-positive BC displays a distinct biological behavior, we aimed to analyze AR expression in the particular context of BC brain metastases (BM)., Materials and Methods: Patients with newly diagnosed BC BM treated with neurosurgical resection were identified from the Vienna Brain Metastasis Registry and clinical data including patient characteristics, biological tumor subtypes and overall survival were obtained by retrospective chart review. Formalin-fixed and paraffin-embedded specimen containing BM tissue were retrieved from the Neuro-Biobank. Immunohistochemical staining of AR was performed and AR expression in the tumor-cell nucleus was evaluated., Results: Fifty-seven BM samples from 57 individual patients with BC were available for this analysis. AR expression of ≥1% tumor cells was evident in 20/57 (35.1%) BM specimens; the median AR-expression rate was 10% (range: 1% to 60%). AR expression was observed in 11/21 (52.4%) BM of the luminal/human epidermal growth factor receptor 2 (HER2)-negative subtype, 3/13 (23.1%) of the luminal/HER2-positive subtype, 2/7 (28.6%) of the HER2-positive subtype and 4/16 (25.0%) of the triple-negative subtype (P=0.247). Median survival from diagnosis of BM was 10 months (range: 0 to 104 mo) in the entire cohort. No significant association of overall survival and AR expression ≥1% was observed (15 vs. 13 mo; P>0.05)., Conclusion: AR is expressed in more than one third of BC BM with the highest rates among the luminal/HER2-negative BC subtype and may therefore be a potential prognostic and predictive biomarker in this particular BC population., Competing Interests: A.S.B. has research support from Daiichi-Sankyo (≤10,000 Euro), Roche (>10000euro) and honoraria for lectures, consultations or advisory board participation from Roche Bristol-Meyers Squibb (all<5000 Euro) as well as travel support from Roche, Amgen and AbbVie. Z.B.-H. reports personal fees from Novartis and Roche and travel support from Roche, outside the submitted work. F.F. has travel and scientific support from Comesa, Novartis, Roche, Astra-Zeneca, Pfizer, Myriad, Nanostring, Bondimed (Polytech, Integra) and honoraria for advisory board participation from Pfizer, Astra-Zeneca, Lilly, and Roche. M.P. has received honoraria for lectures, consultation or advisory board participation from the following for-profit companies: Bayer, Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, Astra-Zeneca, AbbVie, Lilly, Medahead, Daiichi-Sankyo, Sanofi, Merck Sharp & Dome, Tocagen. The following for-profit companies have supported clinical trials and contracted research conducted by M.P. with payments made to his institution: Böhringer-Ingelheim, Bristol-Myers Squibb, Roche, Daiichi-Sankyo, Merck Sharp & Dome, Novocure, GlaxoSmithKline, AbbVie. R.B. has research support from Daiichi-Sankyo, Novartis and Roche, honoraria for lectures from Accord, Astra-Zeneca, BMS, Celgene, Eli-Lilly, Novartis, Pfizer, Roche and Sandoz and honoraria for advisory board participation from Astra-Zeneca, Celgene, Daiichi-Sankyo, Eisai, Eli-Lilly, MSD, Novartis, Pfizer, Roche and Samsung. The remaining authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose/objectives: There is little consensus regarding the application of stereotactic radiotherapy (SRT) in pediatrics. We evaluated patterns of pediatric SRT practice through an international research consortium., Materials and Methods: Eight international institutions with pediatric expertise completed a 124-item survey evaluating patterns of SRT use for patients 21 years old and younger. Frequencies of SRT use and median margins applied with and without SRT were evaluated., Results: Across institutions, 75% reported utilizing SRT in pediatrics. SRT was used in 22% of brain, 18% of spine, 16% of other bone, 16% of head and neck, and <1% of abdomen/pelvis, lung, and liver cases across sites. Of the hypofractionated SRT cases, 42% were delivered with definitive intent. Median gross tumor volume to planning target volume margins for SRT versus non-SRT plans were 0.2 versus 1.4 cm for brain, 0.3 versus 1.5 cm for spine/other bone, 0.3 versus 2.0 cm for abdomen/pelvis, 0.7 versus 1.5 cm for head and neck, 0.5 versus 1.7 cm for lung, and 0.5 versus 2.0 cm for liver sites., Conclusions: SRT is commonly utilized in pediatrics across a range of treatment sites. Margins used for SRT were substantially smaller than for non-SRT planning, highlighting the utility of this approach in reducing treatment volumes.

Therapeutic options for patients with pretreated advanced high-grade glioma (HGG) are limited. Sorafenib, a small molecule with multiple potential beneficial actions, appears particularly promising. We reviewed the outcomes of 30 patients with recurrent or progressive HGG treated with sorafenib within a named patient program. Overall, 16 patients suffered from recurrent or progressive glioblastoma multiforme and 14 patients had grade 3 gliomas. All but four patients had previously undergone surgical debulking; all but one patient had received previous standard multimodal treatment; and 18 patients (60%) had received more than one line of chemotherapy, in median three. Progression-free survival (PFS), defined as the time from initiation of sorafenib to treatment discontinuation because of tumor progression or death, was selected as the endpoint. The use of sorafenib resulted in a median PFS of 3 months [95% confidence interval (CI) 1.9-4.1 months] in patients with glioblastoma and of 3.1 months (95% CI 1.4-4.8 months) in patients with other HGG. The PFS-6 for the whole cohort was 23%. Sixteen patients reported adverse events, mostly moderate, with hypertension as the most frequently reported toxicity (seven patients). One patient died of cerebral bleeding (grade 5 toxicity). The overall survival after initiation of sorafenib was 6 months (95% CI 3.9-8.0 months) for patients with glioblastoma multiforme and 10 months (95% CI 3.1-16.9 months) for patients with HGG. In this retrospective analysis of heavily pretreated patients with HGG, sorafenib monotherapy was associated with tumor stabilization in a small subset of patients. The risk-benefit ratio was acceptable in the context of an apparent clinical benefit in patients with a fatal disease.

We analyzed outcome of a population-based cohort of 74 children with second and third acute lymphoblastic leukemia (ALL) relapse and aimed to identify prognostic factors. Duration of previous remission and site of relapse appeared of prognostic relevance as patients with a second remission duration >1.5 years and isolated extramedullary relapse did better. Neither patient with a second bone marrow relapse who underwent previous allogeneic transplantation nor patients with T-cell ALL survived. Overall, 7 of 74 (9%) patients are in long-term remission. Stem cell transplantation seemed to be the only curative option for systemic relapse of B-cell precursor ALL as all 4 surviving patients with a second/third relapse involving the bone marrow received a transplant. Conclusively, patients with a second ALL relapse are ideal candidates for phase I/II trials exploring new innovative drugs.

Aims: Pathological and clinical data in a large series of immunocompetent patients with primary lymphoma of the central nervous system (PCNSL) were analysed., Methods: We immunostained tumour specimens of 75 patients for CD3, CD4, CD5, CD8, CD10, CD20, CD30, CD79a, Bcl-2, Bcl-6, CD138, MUM1, TDT, PAX5, FOXP1 and Ki-67 and performed in situ hybridisation for Epstein-Barr virus (EBV) RNA. Eleven cases were investigated for rearrangements of BCL6, immunoglobulin heavy chain (IGH) and FOXP1 genes using fluorescent in situ hybridisation (FISH)., Results: Histologically, most cases were classified as diffuse large B-cell lymphoma (80.2%) predominantly of centroblastic type. Immunophenotypic profiling revealed that 96% and 4% of cases corresponded to non-germinal centre and germinal centre type, respectively. FISH analysis showed t(3;14)/IGH-BCL6 in 2/11 cases and trisomy 3 in 2/11 cases. FOXP1 rearrangements were not found. At survival analysis, Karnofsky index >80 and presence of Bcl-6 expression showed independent significant association with favourable patient outcome., Conclusions: PCNSL represents a histologically and immunophenotypically very homogeneous lymphoma type, probably derived from germinal centre exit B cells. The frequent overexpression of FOXP1 appears not to be related to FOXP1 gene rearrangement. Survival analyses disclosed Bcl-6 expression and high Karnofsky performance score as independent prognostic parameters associated with favourable outcome.

We report on a male patient with progressive and metastatic clivus chordoma treated over a period of 9 years by a multidisciplinary approach. Within the first 4 years, the patient underwent surgery four times. Thereafter, he received radiotherapy and subsequent chemotherapy. Stabilization of disease was achieved repeatedly for variable periods under local radiotherapy, systemic chemotherapy, immunomodulatory and anti-angiogenic therapy with isotretinoin and interferon-alpha, followed by thalidomide. Due to the occurrence of brain and lung metastases 8 years after initial diagnosis, liposomal doxorubicin was added to thalidomide. At the last follow-up control the patient had stable disease, with no progression of the intracranial tumor and regression of pulmonary metastases. He is in a good physical, psychological and neurological condition with a Karnofsky score of 80. Our observations show that multimodal therapy including a systemic palliative approach is associated with long quiescent intervals in recurrent chordoma and with regression of its metastases. Use of substances with high efficacy on tumor tissue and low toxicity, allowing long-term administration, seems promising in similar situations.

The aim of this study was to assess the efficacy and toxicity of a combination of dacarbazine (D) and fotemustine (F) administered to a homogenous group of patients with recurrent or progressive glioblastoma multiforme (GBM). Thirty-one patients with computed tomography or magnetic resonance imaging scan evidence of recurrent or progressive GBM after first-line chemotherapy with nitrosoureas as well as radiation therapy were given a combination of D (200 mg/m2) and F (100 mg/m2). At 30 min after termination of D administration, F was given over 60 min. Treatment was performed in an outpatient setting every 21 days. A total of 140 cycles (range 1-12 cycles; median 4 cycles) was administered. One partial response (3%) lasting for 11 weeks was observed. Sixteen (52%) patients reached stable disease lasting between 7 and 94 weeks. Median survival from start of the D/F combination was 45 (range 10-150) weeks. Median time to progression was 17 (3-101) weeks for all patients. Major toxicity was myelosuppression resulting in exclusion from study in seven (23%) patients [due to thrombocytopenia common toxicity criteria (CTC) grade 2 persisting longer than 3 weeks in three patients, due to thrombocytopenia CTC grade >/=3 in three and due to leukopenia CTC grade 3 in one patient]. No other toxicity than alopecia occurred. We conclude that the D/F combination is a well-tolerated second-line regimen and can be administered in a complete outpatient setting. D/F shows efficacy even in nitrosourea-pretreated patients and justifies further investigation.

The aim of this study was to assess survival and prognostic factors of 98 consecutive patients with unresectable glioblastoma multiforme (GBM) after stereotactic biopsy. Patients were diagnosed between 1993 and 1998, and the treatment modality subsequent to stereotactic biopsy was determined by the year of diagnosis. Before 1995, patients did not receive further specific therapy after stereotactic biopsy (n=36). In 1996, patients were administered radiotherapy starting within 6 weeks after stereotactic biopsy (n=24). From 1997 to 1998, patients received combined radio-/chemotherapy (RCT; CCNU orally) starting within 2 weeks after stereotactic biopsy (n=38). Patients' age ranged from 21 to 84 (median 64) years and their median Karnofsky performance score 2 weeks after stereotactic biopsy was 80 (range 60-100). Survival and prognostic factors were analyzed with respect to administered treatment modalities (without specific therapy versus radiotherapy versus combined RCT), with respect to age (>oror=or<80), tumor location (frontal, parieto-temporal, central, occipital) and tumor size (>or5 cm) by the Kaplan-Meier method, by log-rank test and multivariate Cox regression analysis. Post-biopsy treatment modality was the strongest predictor for survival. Median (range) survival was 9 (3-47) weeks in those without specific therapy, 13 (5-54) weeks in patients receiving radiotherapy and 31 (11-101) weeks in patients receiving combined RCT (p

In our institution, 103 glioblastoma multiforme (GBM) patients aged from 55 to 83 years were treated since November 1994 as follows. All patients underwent surgical intervention (gross total resection, n = 35; subtotal resection, n = 38; stereotactic biopsy, n = 30). Subsequently all patients were offered radiotherapy and chemotherapy with CCNU. Results were as follows: 101 patients started radiotherapy, 93 patients completed it (96% of the patients aged < 65 years and 85% of the patients > or =65 years). All patients received at least 1 cycle of chemotherapy (median 3 cycles). Chemotherapy-associated toxicity was generally mild, more pronounced in females and did not increase with age. Median time to progression was 10.5+/-3.2 months for the patients < 65 years and 5.1+/-1 months for patients > or =65 years. median overall survival was 17.5+/-3.8 months in patients < 65 years and 8.6+/-1 months in patients > or =65 years (p < 0.0001). In multivariate analysis, age and female sex remained independent prognostic factors. Our data indicate that a treatment concept including concomitant radio- and chemotherapy is feasible even in elderly patients with GBM., (Copyright 2003 Lippincott Williams & Wilkins)