The role of stereotactic conformal radiation boost in the temozolomide-based chemoradiation for glioblastoma multiforme: Preliminary analysis

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 12513-12513
Author(s):  
M. Balducci ◽  
S. Manfrida ◽  
G. R. D’Agostino ◽  
C. Anile ◽  
L. Azario ◽  
...  

12513 Background: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. Aim of this analysis was to evaluate tolerance and outcome of the dose intensification by stereotactic conformal radiotherapy (SCRT) and concomitant chemotherapy with temozolomide Methods: From October 2003 to April 2006, 58 patients (34 males, 58.6%, 24 females, 41.4%) with histological diagnosis of glioblastoma multiforme received postoperative radiochemotherapy with SCRT boost. Median age was 58 yrs. ( range 25–80 yrs.). Twenty-nine out of 58 patients (50%) received a total dose of 70 Gy by conformal radiotherapy and SCRT boost delivered as concomitant and sequential, or sequential alone. The remainig 29 patients (50%) received a standard of 5940 cGy (180 cGy/day; CTV3: tumor bed + residual tumor if present + oedema; CTV2: tumor bed + residual tumor if present + 1.5 cm margins. CTV1: tumor bed + residual tumor if present + 0.5 cm margins only for the SCRT group). All patients received concomitant Temozolomide, 75 mg/m2 for a median duration of 28 days (range 14–45, depending on the chemoradiation schedule), and adjuvant chemotherapy with temozolomide for 6 cycles or until disease progression. Toxicity was recorded according to RTOG criteria; Survival analysis was calculated by the Kaplan-Mayer method and log-rank testing was used for groups comparison. Results: A 100% compliance was observed in both the groups of patients. A grade 3–4 acute neurological toxicity was registered in two patients treated with SCRT compared to one patient in the group which did not receive SCRT. One case of radionecrosis was observed in the SCRT group; in no case of either group neurological worsening nor corticosteroidal dependence were registered. At a median follow-up of 19 months (range 4–39), a trend towards a better outcome was observed in patients treated with SCRT, since the 1-year OS was 85.9% for SCRT patients (median not achieved) compared to 68.7% for the remaining patients (p=0.07). Conclusion: Our preliminary analysis suggests that a higher dose of RT delivered by conformal stereotactic boost did not increase acute or late toxicity and could achieve a better outcome in patients affected by GBM No significant financial relationships to disclose.

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 12516-12516
Author(s):  
S. Manfrida ◽  
G. R. D’Agostino ◽  
C. Anile ◽  
G. Mantini ◽  
G. Colicchio ◽  
...  

12516 Background: We retrospectively evaluate the tolerance and the efficacy of a conventional schedule of radiotherapy in elderly patients with glioblastoma multiforme (GBM). Methods: Eighty-three consecutive patients affected by glioblastomas were treated between 2001 and 2006. We divided our series in two groups: patients under 65 years (n=52) and patients ≥ 65 years old (n=31). In the elderly group, median age was 68 years (range, 65–80). 17 patients (54,8%) were female, 14 male (45,2%); 20 patients (64,5%) <70 years, 11 patients (35,5%) ≥70 years. Among the younger patients, median age was 51 years (range 25–64), male/female ratio 32/20 (61.5%/38.5%).Twenty-seven out of 31 elderly patients (87,1%) were treated with conformal radiotherapy (CRT, 5940 cGy, 180 cGy/day; CTV2: tumor bed + residual tumor if present + oedema, 3960 cGy; CTV1: tumor bed + residual tumor if present + margins, 1980 cGy). Four out of 31 patients received an intensification dose of xxxx cGy by stereotactic conformal radiotherapy (SRT, 12,9%); among the younger patients, 25/52 were treated with CRT (48,1%) and 27/52 with SRT (51,9%). Concomitant and adjuvant chemotherapy was administered by temozolomide (TMZ).Toxicity was evaluated according to RTOG score. Survival analysis were performed using Kaplan-Meier method and log-rank testing was used for comparison of groups. Results: In the elderly group, neurological acute toxicity was observed in 6/31 patients (19,4%), with grade 3 in two patients. In the under 65 group, 5/52 patients (9,6%) had neurotoxicity (Grade 3 in two patients).This difference was not statistically different.At a median follow-up period of 28 months (range, 3–61), median progression-free survival (PFS) was 11 months in the ≥65 group and 10 months in the under 65 group; median overall survival (OS) was respectively 17 months and 22 months. 1- year survival was respectively 77.6% and 74.5%. Conclusions: In our analysis age did not seem to be a limiting factor in the choice of the therapeutic strategy for patients with glioblastoma multiforme. No significant financial relationships to disclose.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13000-e13000
Author(s):  
Eluska Iruarrizaga ◽  
Eider Azkona ◽  
Unai Aresti ◽  
Itziar Rubio ◽  
Mikel Arruti ◽  
...  

e13000 Background: Glioblastoma multiforme constitutes the most common and malignant form of primary brain tumor. Median survival for recurrent disease is 3-9 months. Combining bevacizumab with irinotecan represents an option of treatment in recurrent GBM. Methods: We performed a retrospective review of patients with recurrent GBM treated with bevacizumab (10 mg/kg) and irinotecan (340 mg/m2 for patients receiving enzyme-inducing antiepileptic drugs –EIAEDs- and 125 mg/m2 for patients not receiving EIAEDs) every 14 days on a 4-week cycle. Inclusion criteria: age ≥ 18, histology of GBM, progression after radiotherapy and temozolomide and signed informed consent for bevacizumab compassionate use. MRI-FLAIR sequence was used every 8 weeks to assess response. Results: From October 2009 to December 2012, a total of 26 patients were included; 15 (57.7%) male/11 (42.3%) female. Median age of the patients was 52 years (32-69); ECOG 0/1/2/3: 7.7/46.2/38.5/7.7% respectively; 19.23 % of patients received EIAEDs. Median number of cycles was 2.5 (1-14). Response rate was 30.8% (23.1% PR; 7.7 % CR); SD 23.1 %. Median PFS was 23 weeks; median OS was 30 weeks. Most common grade 3 toxicities were: asthenia 26.9%, arthromyalgia 3.8%, diarrhea 3.8% and hepatotoxicity 15.4%; grade 2 thromboembolic complications: 3.8 %. Conclusions: Combination of bevacizumab and irinotecan is effective against recurrent GBM and prolongs PFS and OS compared with historical controls, with mild toxicity.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Giovanna Mantini ◽  
Sergio Fersino ◽  
Anna Rita Alitto ◽  
Vincenzo Frascino ◽  
Mariangela Massaccesi ◽  
...  

Purpose. To perform a preliminary feasibility acute and late toxicity evaluation of an intensified and modulated adjuvant treatment in prostate cancer (PCa) patients after radical prostatectomy.Material and Methods. A phase I/II has been designed. Eligible patients were 79 years old or younger, with an ECOG of 0–2, previously untreated, histologically proven prostate adenocarcinoma with no distant metastases, pT2–4 N0-1, and with at least one of the following risk factors: capsular perforation, positive surgical margins, and seminal vesicle invasion. All patients received a minimum dose on tumor bed of 64.8 Gy, or higher dose (70.2 Gy; 85.4%), according to the pathological stage, pelvic lymph nodes irradiation (57.7%), and/or hormonal therapy (69.1%).Results. 123 patients were enrolled and completed the planned treatment, with good tolerance. Median follow-up was 50.6 months. Grade 3 acute toxicity was only 2.4% and 3.3% for genitourinary (GU) and gastrointestinal (GI) tract, respectively. No patient had late grade 3 GI toxicity, and the GU grade 3 toxicity incidence was 5.8% at 5 years. 5-year BDSF was 90.2%.Conclusions. A modulated and intensified adjuvant treatment in PCa was feasible in this trial. A further period of observation can provide a complete assessment of late toxicity and confirm the BDSF positive results.


Author(s):  
Gianluca Agresta ◽  
Alberto Campione ◽  
Fabio Pozzi ◽  
Pierlorenzo Veiceschi ◽  
Martina Venturini ◽  
...  

Abstract Objective We illustrate a cavernous sinus chondrosarcoma treated with an endoscopic endonasal transethmoidal-transsphenoidal approach. Design Case report of a 15-year-old girl with diplopia and esotropia due to complete abducens palsy. Preoperative images showed a right cavernous sinus lesion with multiple enhanced septa and intralesional calcified spots (Fig. 1). Considering tumor location and the lateral dislocation of the carotid artery, an endoscopic endonasal approach was performed to relieve symptoms and to optimize the target geometry for adjuvant conformal radiotherapy. Setting The study was conducted at University of Insubria, Department of Neurosurgery, Varese, Italy. Participants Skull base team was participated in the study. Main Outcome Measures A transethmoidal-transsphenoidal approach was performed by using a four-hand technique. We used a route lateral to medial turbinate to access ethmoid and the sphenoid sinus. During the sphenoid phase, we exposed the medial wall of the cavernous sinus (Fig. 2) and the lesion was then removed using curette. Skull base reconstruction was performed with fibrin glue and nasoseptal flap. Results No complications occurred after surgery, and the patient experienced a complete recovery of symptoms. A postoperative magnetic resonance imaging showed a small residual tumor inside the cavernous sinus (Fig. 1). After percutaneous proton-bean therapy, patient experienced only temporary low-grade toxicity with local control within 2 years after treatment completion. Conclusion Endoscopic endonasal extended approach is a safe and well-tolerated procedure that is indicated in selected cases (intracavernous tumors, soft tumors not infiltrating the vessels and/or the nerves). A tailored approach according to tumor extension is crucial for the best access to the compartments involved.The link to the video can be found at: https://youtu.be/TsqXjqpuOws.


Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1411
Author(s):  
Don Carlo Ramos Batara ◽  
Moon-Chang Choi ◽  
Hyeon-Uk Shin ◽  
Hyunggee Kim ◽  
Sung-Hak Kim

Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumor in adults, with a poor median survival of approximately 15 months after diagnosis. Despite several decades of intensive research on its cancer biology, treatment for GBM remains a challenge. Autophagy, a fundamental homeostatic mechanism, is responsible for degrading and recycling damaged or defective cellular components. It plays a paradoxical role in GBM by either promoting or suppressing tumor growth depending on the cellular context. A thorough understanding of autophagy’s pleiotropic roles is needed to develop potential therapeutic strategies for GBM. In this paper, we discussed molecular mechanisms and biphasic functions of autophagy in gliomagenesis. We also provided a summary of treatments for GBM, emphasizing the importance of autophagy as a promising molecular target for treating GBM.


Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2598
Author(s):  
Lisa Maria Walchhofer ◽  
Ruth Steiger ◽  
Andreas Rietzler ◽  
Johannes Kerschbaumer ◽  
Christian Franz Freyschlag ◽  
...  

Background: Glioblastoma multiforme (GBM) is a highly malignant primary brain tumor with infiltration of, on conventional imaging, normal-appearing brain parenchyma. Phosphorus magnetic resonance spectroscopy (31P-MRS) enables the investigation of different energy and membrane metabolites. The aim of this study is to investigate regional differences of 31P-metabolites in GBM brains. Methods: In this study, we investigated 32 patients (13 female and 19 male; mean age 63 years) with naïve GBM using 31P-MRS and conventional MRI. Contrast-enhancing (CE), T2-hyperintense, adjacent and distant ipsilateral areas of the contralateral brain and the brains of age- and gender-matched healthy volunteers were assessed. Moreover, the 31P-MRS results were correlated with quantitative diffusion parameters. Results: Several metabolite ratios between the energy-dependent metabolites and/or the membrane metabolites differed significantly between the CE areas, the T2-hyperintense areas, the more distant areas, and even the brains of healthy volunteers. pH values and Mg2+ concentrations were highest in visible tumor areas and decreased with distance from them. These results are in accordance with the literature and correlated with quantitative diffusion parameters. Conclusions: This pilot study shows that 31P-MRS is feasible to show regional differences of energy and membrane metabolism in brains with naïve GBM, particularly between the different “normal-appearing” regions and between the contralateral hemisphere and healthy controls. Differences between various genetic mutations or clinical applicability for follow-up monitoring have to be assessed in a larger cohort.


2016 ◽  
Author(s):  
Chaitanya Medichelme ◽  
Shagun Juneja ◽  
Anirudh Punnakal ◽  
Charu Garg ◽  
Indu Bansal ◽  
...  

Purpose: The aim of this study is to report a preliminary analysis of our clinical experience with extended field pelvic (conformal) radiation, with or without concurrent chemotherapy, in gynaecological malignancies. Materials and Methods: 27 women with gynaecological malignancies (17 with Carcinoma Cervix and 10 with Carcinoma Endometrium) were treated between November 2009 and October 2015 with Extended Field abdomino-pelvic radiation. All patients were treated with conformal radiation (Intensity Modulated Radiotherpy or Volumetric Modulated Arc Therapy). All patients underwent CT Simulation followed by target and OAR delineation as per RTOG guidelines. Dose prescriped was 45-50 Gy in 1.8 Gy per fraction and boost to gross node upto 54-56 Gy. Planning was done on Eclipse Planning system, and treatment was delivered on 6 MV linac. Concurrent chemotherapy was given when indicated. All toxicities were scored according to Common Terminology Criteria for Adverse Events (CTCAE v 4.03). Dosimetric parameters were correlated with toxicities. Results: Median follow up was 9.5 months (Range 0-52 months). 14 (51.8%) patients developed Grade 1 and 2 acute hematological toxicity and 1 (0.04%) developed Grade 3 toxicity. 10 (37%) patients developed Grade 1 and 2 acute gastrointestinal toxicity and 1 (0.04%) developed grade 4 toxicity. 3 (11.12%) patients had late toxicity in the form of prolonged leucopenia, SAIO, and Irritable Bowel Syndrome. 1 patient did not complete her treatment due to persistent leucopenia (Grade 3). Conclusion: Extended field Radiation in Gynaecological malignancies is a reasonably well tolerated procedure when treated with IMRT or VMAT, with acceptable toxicity profile.


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii387-iii387
Author(s):  
Andrey Levashov ◽  
Dmitry Khochenkov ◽  
Anna Stroganova ◽  
Marina Ryzhova ◽  
Sergey Gorelyshev ◽  
...  

Abstract The aim of this study was to estimate treatment toxicity and event-free survival (EFS) according to therapeutic program, MYC/MYC-N gene amplification and MGMT/DNMT (1, 3a, 3b) proteins expression in tumor cells. From 2016 to 2018 twenty four patients were included in trial. Children underwent adjuvant therapy: craniospinal radiation (CSI) or local radiation therapy (RT) to the relapsed site up to 23.4Gy with 5-azacytidine, 2 cycles methotrexate/5-azacytidine/cisplatin/etoposide, 3 cycles 5-azacytidine/temozolomide - for relapsed group (arm A, n = 5); for patients with de novo medulloblastoma: arm B, n = 11 – vincristine/cyclophosphamide/cisplatin/etoposide (OPEC) - based induction, CSI 36Gy + local RT to the tumor bed up to 54Gy with 5-azacytidine, 1 cycle OPEC and 2 cycles thiophosphamide/carboplatin with auto stem cell transplantation (auto-SCT); arm C, n = 8 – cyclophosphamide/cisplatin - based induction, CSI 23.4 Gy followed by 2 cycles 5-azacytidine/thiophosphamide/carboplatin with auto-SCT, local RT with 5-azacytidine. The combination of 5-azacytidine with local RT or temozolomide was safety and tolerability. Arm C was discontinued due to severe gastrointestinal grade 3/4 toxicity, hemorrhagic syndrome after combination of 5-azacytidine with thiophosphamide/carboplatin. EFS was 0% in arm A, 53.0 ± 15.5%, 50.0 ± 17.7% in arms B and C, a median follow-up 8.8 ± 1.1 months (arm A), 18.8 ± 2.5 months (arm B), 25.0 ± 4.4 months (arm C). Addition of 5-azacytidine to RT or chemotherapy did not improve EFS of patients with MYC/MYC-N gene amplification positive tumor. There was not determined any prognostic significance of MGMT/DNMT (1, 3a, 3b) proteins expression in this cohort.


2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi31-vi31
Author(s):  
Christof Fellmann ◽  
I-Li Tan ◽  
Alexendar Perez ◽  
Rachel Lew ◽  
Karen Zhu ◽  
...  

Abstract Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults 1. Despite multimodal treatment regimens including surgical resection, radio- and chemotherapy, the growth of residual tumor often results in therapy resistance and ultimately death. GBMs are highly diffuse and exhibit extensive intratumoral heterogeneity 2,3, confounding diagnostic efforts and presenting opportunities for therapy evasion. Therefore, innovative treatment paradigms that can efficiently eliminate GBM cells irrespective of their mutational and epigenetic profile are urgently needed. CRISPR technologies have revolutionized medicine by enabling targeted genome editing through RNA-guided introduction of DNA double-strand breaks 4,5. Here, we show that CRISPR-Cas9 mediated genome fragmentation through targeting of highly repetitive loci, termed “genome shredding”, enables rapid and robust elimination of GBM cells. We characterized genome shredding across mammalian and vertebrate cells, and identified optimal repetitive pan-vertebrate and species-specific loci. Genome shredding is equally effective in temozolomide (TMZ)-sensitive and -resistant GBM cells, and multi-cycle treatment regimens are feasible. Importantly, when deployed in intracerebral GBM xenografts through local delivery, CRISPR-Cas9 genome shredding efficiently eliminated all targeted cells. Together, genome shredding enables the rapid and efficient fragmentation of a target cell’s genome and subsequent DNA damage-induced cell death. This provides an innovative treatment paradigm that is independent of a tumor’s mutational and epigenetic profile and leverages CRISPR-Cas9 as a breakthrough therapeutic modality for GBM.


Author(s):  
Lauren VanderSpek ◽  
Barbara Fisher ◽  
Glenn Bauman ◽  
David Macdonald

Purpose:To determine the maximum tolerated dose of 3D conformal radiotherapy in combination with Cisplatin for patients with recurrent malignant gliomas.Methods:From 1999-2003, nine patients with recurrent malignant glioma received fractionated radiotherapy and Cisplatin (20 mg/m2/d IV on days 1-5) in a Phase I radiation dose escalation trial. Three sequential dose levels were evaluated: 25 Gy, 30 Gy, and 35 Gy, using 5 Gy fractions. All patients received prior external beam radiation (median dose 59.4 (20-60) Gy) and five patients received prior chemotherapy.Results:Six male and three female patients were enrolled with a median age of 52 years, and a median Karnofsky performance status score of 70. The median re-irradiated tumor volume was 18.9 (0.1-78.5) cm3 and the median follow-up was 8.8 (3.2-31.2) months. One patient (30 Gy/ 6 fractions) experienced medically reversible acute grade 3 toxicity. A second patient (35 Gy/ 7 fractions) experienced acute grade 2 toxicity and histology showed tumor and radiation effect. A third patient (25 Gy/ 5 fractions) experienced late grade 3 toxicity from radiation necrosis. The radiological responses consisted of complete response (1 patient), partial response (1 patient), and stable disease (2 patients). The median overall survival was 8.8 months (95% CI 8.0-9.9), and the median disease free interval was 2.0 months (95% CI 1.4-4.4). Seven patients received chemotherapy following re-irradiation and Cisplatin.Conclusion:The maximum tolerated dose of 3D conformal fractionated radiotherapy was 30 Gy in 6 fractions with low dose Cisplatin, which was well tolerated in terms of acute toxicity for our patient population. This regimen demonstrated only modest efficacy in the treatment of recurrent malignant glioma. Combinations of conformal re-irradiation and other systemic agents may merit investigation. Currently our recommended dose is 30 Gy in 6 fractions for selected patients.


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