FLAIRectomy in Supramarginal Resection of Glioblastoma Correlates With Clinical Outcome and Survival Analysis: A Prospective, Single Institution, Case Series

2020 ◽  
Author(s):  
Francesco Certo ◽  
Roberto Altieri ◽  
Massimiliano Maione ◽  
Claudio Schonauer ◽  
Giuseppe Sortino ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Dna Methyltransferase ◽  
Aminolevulinic Acid ◽  
Intraoperative Imaging ◽  
Tumor Resection ◽  
Case Series ◽  
Progression Free Survival ◽  
Residual Tumor ◽  
Volumetric Analysis ◽  
Mr Images

Abstract Background Extent of tumor resection (EOTR) in glioblastoma surgery plays an important role in improving survival. Objective To analyze the efficacy, safety and reliability of fluid-attenuated inversion-recovery (FLAIR) magnetic resonance (MR) images used to guide glioblastoma resection (FLAIRectomy) and to volumetrically measure postoperative EOTR, which was correlated with clinical outcome and survival. Methods A total of 68 glioblastoma patients (29 males, mean age 65.8) were prospectively enrolled. Hyperintense areas on FLAIR images, surrounding gadolinium-enhancing tissue on T1-weighted MR images, were screened for signal changes suggesting tumor infiltration and evaluated for supramaximal resection. The surgical protocol included 5-aminolevulinic acid (5-ALA) fluorescence, neuromonitoring, and intraoperative imaging tools. 5-ALA fluorescence intensity was analyzed and matched with the different sites on navigated MR, both on postcontrast T1-weighted and FLAIR images. Volumetric evaluation of EOTR on T1-weighted and FLAIR sequences was compared. Results FLAIR MR volumetric evaluation documented larger tumor volume than that assessed on contrast-enhancing T1 MR (72.6 vs 54.9 cc); residual tumor was seen in 43 patients; postcontrast T1 MR volumetric analysis showed complete resection in 64 cases. O6-methylguanine-DNA methyltransferase promoter was methylated in 8/68 (11.7%) cases; wild type Isocytrate Dehydrogenase-1 (IDH-1) was found in 66/68 patients. Progression free survival and overall survival (PFS and OS) were 17.43 and 25.11 mo, respectively. Multiple regression analysis showed a significant correlation between EOTR based on FLAIR, PFS (R2 = 0.46), and OS (R2 = 0.68). Conclusion EOTR based on FLAIR and 5-ALA fluorescence is feasible. Safety of resection relies on the use of neuromonitoring and intraoperative multimodal imaging tools. FLAIR-based EOTR appears to be a stronger survival predictor compared to gadolinium-enhancing, T1-based resection.

5-Aminolevulinic Acid and Contrast-Enhanced Ultrasound: The Combination of the Two Techniques to Optimize the Extent of Resection in Glioblastoma Surgery

Neurosurgery ◽  
2020 ◽  
Vol 86 (6) ◽  
pp. E529-E540 ◽  
Author(s):  
Giuseppe Maria Della Pepa ◽  
Tamara Ius ◽  
Giuseppe La Rocca ◽  
Simona Gaudino ◽  
Miriam Isola ◽  
...  
Keyword(s):  
Aminolevulinic Acid ◽  
Imaging Techniques ◽  
Intraoperative Imaging ◽  
Progression Free Survival ◽  
Residual Tumor ◽  
Extent Of Resection ◽  
Contrast Enhanced Ultrasound ◽  
Technological Advances ◽  
Contrast Enhanced ◽  
Tumor Identification

Abstract BACKGROUND The survival benefit in maximizing resection in glioblastomas (GBMs) has been demonstrated by numerous studies. The true limit of infiltration of GBMs has been an overwhelming obstacle, and several technological advances have been introduced to improve the identification of residual tumors. OBJECTIVE To evaluate whether the integration of 5-aminolevulinic acid (5-ALA) with microbubble contrast-enhanced ultrasound (CEUS) improves residual tumor identification and has an impact on the extent of resection (EOR), overall survival (OS), and progression-free survival (PFS). METHODS A total of 230 GBM procedures were retrospectively studied. Cases were stratified according to the surgical procedure into 4 groups: 5-ALA- and CEUS-guided surgeries, 5-ALA-guided surgeries, CEUS-guided surgeries, and conventional microsurgical procedures. RESULTS Patients undergoing conventional microsurgical procedures showed the worst EORs compared to the assisted techniques (5-ALA and CEUS procedures). Both 5-ALA and CEUS techniques improved the EOR compared to conventional microsurgical procedures. However, their combination gave the best results in terms of the EOR (P = .0003). The median EOR% and the number of supramarginal resections are hence superior in the 5-ALA + CEUS + group compared to the others; this observation had consequences on PFS and OS in our series. CONCLUSION In terms of the EOR, the best results can be achieved through a combination of both techniques, where the 5-ALA-guided procedure is followed by a final survey with CEUS. Compared with other intraoperative imaging techniques, CEUS is a real-time, readily repeatable, safe, and inexpensive technique that provides valuable information to the surgeon before, during, and after resection.

scholarly journals NIMG-06. OUR THERAPEUTIC STRATEGIES FOR GLIOBLASTOMA: INTRAOPERATIVE SUPPORT SYSTEMS [INTRAOPERATIVE MRI, PET, 5-AMINOLEVULINIC ACID (5-ALA)] AND NEOADJUVANT CHEMOTHERAPY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi162-vi162
Author(s):  
Keisuke Miyake ◽  
Daisuke Ogawa ◽  
Masaki Okada ◽  
Tetsuhiro Hatakeyama ◽  
Takashi Tamiya
Keyword(s):  
Pet Imaging ◽  
Aminolevulinic Acid ◽  
Performance Status ◽  
Progression Free Survival ◽  
Residual Tumor ◽  
Extraction Rate ◽  
Intraoperative Mri ◽  
Positron Emission ◽  
Magnetic Resonance Imaging Mri ◽  
Tumor Extraction

Abstract OBJECTIVE Neuronavigation systems with magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging (methionine [MET], fluorothymidine [FLT], and fluoromisonidazole [FMISO]) are routinely used in glioblastoma surgery. Residual tumor identified using intraoperative MRI (IoMRI) or 5-aminolevulinic acid (5-ALA) fluorescence is removed. Neoadjuvant bevacizumab therapy is offered to patients with low Karnovsky performance status (KPS) or with tumors in eloquent regions. We evaluated the usefulness of neoadjuvant bevacizumab therapy. METHODS Twelve patients with glioblastoma with low KPS or tumors in eloquent regions on multiple PET and IoMRI evaluations were enrolled between January 2016 and April 2019. Six had received neoadjuvant bevacizumab before surgery; six had not. Postsurgical 5-ALA fluorescence (strong, vague, and none) tumor extraction rate, residual volume on MRI and PET imaging, and prognosis in the patients with and without bevacizumab were compared. RESULTS In patients with bevacizumab adjuvant therapy, the KPS scores immediately prior to surgery were 90 in 3 cases, 80 in 2, and 70 in 1. The scores in patients without bevacizumab were 50 in 2 and 40 in 4. The 5-ALA fluorescence in patients with bevacizumab was vague in one and none in five. Vague fluorescence was noted in all six patients without bevacizumab. Tumor extraction rates in patients with vs. those without bevacizumab were 97.6% vs. 91.5% by T1-Gd, 95.4% vs. 99.9% by MET, 96.2% vs. 90.2% by FLT, and 97% vs. 92% by FMISO. Corresponding residual volumes (ml) were (0.6 vs. 1.7) for T1-Gd, 1.2 vs. 2.9 for MET, 1.0 vs. 2.1 for FLT, and 0.5 vs. 1.1 for. FLT. Median progression free survival (PFS) was 10.1 vs. 4.9 months; median overall survival (OS) was 15.7 vs. 13.3 months. CONCLUSIONS Neoadjuvant bevacizumab therapy improved KPS at the time of surgery, increased extraction rate, reduced residual tumor volume, and improved PFS and OS prognosis.

Endoscopic Fluorescence-Guided Resection Increases Radicality in Glioblastoma Surgery

2019 ◽  
Vol 18 (1) ◽  
pp. 41-46 ◽  
Author(s):  
Christoph Bettag ◽  
Abdelhalim Hussein ◽  
Daniel Behme ◽  
Theoni Maragkou ◽  
Veit Rohde ◽  
...  
Keyword(s):  
Tumor Tissue ◽  
Aminolevulinic Acid ◽  
Histopathological Examination ◽  
Tumor Resection ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
Complete Resection ◽  
Free Survival ◽  
Resected Tissue ◽  
Microsurgical Resection

Abstract BACKGROUND Several studies have proven the benefit of a greater extent of resection on progression-free survival and overall survival in glioblastoma (GBM). Possible reasons for incomplete tumor resection might be wrong interpretation of fading fluorescence or overseen fluorescent tumor tissue by a lacking line of sight between tumor tissue and the microscope. OBJECTIVE To evaluate if an endoscope being capable of inducing fluorescence might overcome some limitations of microscopic fluorescence-guided (FG) resection. METHODS 5-Aminolevulinic acid (20 mg/kg) was given 4 h before surgery. Microsurgical resection of all fluorescent tissue was performed. Then, the resection cavity was scanned with the endoscope. Fluorescent tissue, not being visualized by the microscope, was additionally removed and histopathologically examined separately. Neuronavigation was used for defining the sites of additional tumor resection. All patients underwent magnetic resonance imaging within 48 h after surgery. RESULTS Twenty patients with GBM were operated using microscopic and endoscopic FG resection. In all patients, additional fluorescent tissue was detected with the endoscope. This tissue was completely resected in 19 patients (95%). Eloquent localization precluded complete resection in the remaining patient. In 19 patients (95%), histopathological examination confirmed tumor in the additionally resected tissue. In 19 patients (95%), complete resection was confirmed. In all patients, endoscopic FG resection reached beyond the borders of contrast-enhancing tumor. CONCLUSION Endoscopic FG resection of GBM allows increasing the complete resection rate substantially and therefore is a useful adjunct to microscopic FG resection.

Fluorescence-guided resection of glioblastoma multiforme utilizing 5-ALA-induced porphyrins: a prospective study in 52 consecutive patients

2000 ◽  
Vol 93 (6) ◽  
pp. 1003-1013 ◽  
Author(s):  
Walter Stummer ◽  
Alexander Novotny ◽  
Herbert Stepp ◽  
Claudia Goetz ◽  
Karl Bise ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Mr Imaging ◽  
Aminolevulinic Acid ◽  
Univariate Analysis ◽  
Tumor Resection ◽  
Mr Images ◽  
Content Type ◽  
Tissue Fluorescence ◽  
Solid Fluorescence ◽  
Fine Print

Object. It has been established that 5-aminolevulinic acid (5-ALA) induces the accumulation of fluorescent porphyrins in glioblastoma multiforme (GBM), a phenomenon potentially exploitable to guide tumor resection. In this study the authors analyze the influence of fluorescence-guided resection on postoperative magnetic resonance (MR) imaging and survival in a series of patients who underwent surgery in the authors' department.Methods. Fifty-two consecutive patients with GBM received oral doses of 5-ALA (20 mg/kg body weight) 3 hours before induction of anesthesia. Intraoperatively, tumor fluorescence was visualized using a modified operating microscope. Fluorescing tissue was removed whenever it was considered safely possible. Residual enhancement on early postoperative MR imaging was quantified and related to each patient's characteristics to determine which factors influenced resection. Survival was analyzed using the Kaplan—Meier method and multivariate analysis was performed in which the Karnofsky Performance Scale (KPS) score, residual fluorescence, patient age, and residual enhancement on MR images were considered.Intraoperatively, two fluorescence qualities were perceived: solid fluorescence generally reflected coalescent tumor, whereas vague fluorescence mostly corresponded to infiltrative tumor. Complete resection of contrast-enhancing tumor was accomplished in 33 patients (63%). Residual intraoperative tissue fluorescence left unresected for safety reasons predicted residual enhancement on MR images in 18 of the 19 remaining patients. Age, residual solid fluorescence, and absence of contrast enhancement in MR imaging were independent explanatory factors for survival, whereas the KPS score was significant only in univariate analysis. No perioperative deaths and one case of permanent morbidity were encountered.Conclusions. The observations in this study indicate the usefulness of 5-ALA—induced tumor fluorescence for guiding tumor resection. The completeness of resection, as determined intraoperatively from residual tissue fluorescence, was related to postoperative MR imaging findings and to survival in patients suffering from GBM.

Phase I/IIa trial of cilengitide (EMD121974) and temozolomide with concomitant radiotherapy, followed by temozolomide and cilengitide maintenance therapy in patients (pts) with newly diagnosed glioblastoma (GBM)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2000-2000 ◽  
Author(s):  
R. Stupp ◽  
R. Goldbrunner ◽  
B. Neyns ◽  
U. Schlegel ◽  
P. Clement ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Dna Methyltransferase ◽  
Methylation Status ◽  
Tumor Resection ◽  
Gene Promoter ◽  
Progression Free Survival ◽  
Liver Function Tests ◽  
Mri Imaging ◽  
Mgmt Gene ◽  
Grade 3

2000 Background: To evaluate safety, toxicity, and efficacy of the combination of the cyclic RGD pentapeptide cilengitide (EMD121974), an inhibitor of integrins avβ3 and avβ5, in addition to standard temozolomide (TMZ) and radiotherapy (RT). Methods: 52 pts (PS 0–1: 92%, 2: 8%; median age 57 yrs) after tumor resection (n=43/83%) or biopsy (n= 9/17%) were treated with standard TMZ/RT (Stupp et al. NEJM 2005). In addition cilengitide (500 mg i.v., 2x/week) was started one week before TMZ/RT and given throughout for the duration of chemotherapy or until progression. The primary endpoint was progression free survival rate at 6 months (target: 65%). Pts were followed with MRI every 2 months. Histopathologic diagnosis and MRI imaging were independently reviewed, O6-Methylguanine- DNA methyltransferase (MGMT) promotor methylation status was assessed in 45 (86.5%) pts. Results: 46 pts (92%) completed RT, = 90% of concomitant TMZ was received by 42 pts and cilengitide by 45 pts. 20 pts (3 ongoing) completed 6 cycles of maintenance TMZ and cilengitide. Observed hematological grade 3 and 4 toxicities were: lymphopenia (28/52, 53.8%), thrombocytopenia (7/52 pt. 13.4%) and neutropenia (5/52, 9.6%). Treatment related non-hematologic grade 3/4 toxicities were reported for n=3/52 (5.7%) patients: constitutional symptoms (asthenia, fatigue, anorexia, n=3); elevated liver function tests (n=1), deep venous thrombosis and pulmonary embolism (n=1). One patient with a history of sigmoid diverticulosis experienced sigmoid perforation (grade 2). In total, 34/52 (65.4% [95% CI, 50.9–78.0%]) of the pts were progression free at 6 months. Pts with MGMT gene-promotor methylation in the tumor were more likely to reach 6 months PFS endpoint. Conclusions: The study reached its primary endpoint. The combination of the integrin inhibitor RGD peptide Cilengitide and TMZ/RT was well tolerated, PFS at 6 months is encouraging. MGMT gene promoter methylation correlates with outcome. At the time of ASCO, updated results and survival estimates after a minimum follow-up of at least 1 year will be available. [Table: see text]

Intraoperative Probe-Based Confocal Laser Endomicroscopy in Surgery and Stereotactic Biopsy of Low-Grade and High-Grade Gliomas

Neurosurgery ◽  
2016 ◽  
Vol 79 (4) ◽  
pp. 604-612 ◽  
Author(s):  
Vladislav Pavlov ◽  
David Meyronet ◽  
Vincent Meyer-Bisch ◽  
Xavier Armoiry ◽  
Brian Pikul ◽  
...  
Keyword(s):  
Open Surgery ◽  
Stereotactic Biopsy ◽  
Aminolevulinic Acid ◽  
Intraoperative Imaging ◽  
Intraoperative Complications ◽  
Tumor Resection ◽  
Confocal Laser Endomicroscopy ◽  
Confocal Laser ◽  
Low Grade ◽  
Histologic Diagnosis

Abstract BACKGROUND: The management of gliomas is based on precise histologic diagnosis. The tumor tissue can be obtained during open surgery or via stereotactic biopsy. Intraoperative tissue imaging could substantially improve biopsy precision and, ultimately, the extent of resection. OBJECTIVE: To show the feasibility of intraoperative in vivo probe-based confocal laser endomicroscopy (pCLE) in surgery and biopsy of gliomas. METHODS: In our prospective observational study, 9 adult patients were enrolled between September 2014 and January 2015. Two contrast agents were used: 5-aminolevulinic acid (3 cases) or intravenous fluorescein (6 cases). Intraoperative imaging was performed with the Cellvizio system (Mauna Kea Technologies, Paris). A 0.85-mm probe was used for stereotactic procedures, with the biopsy needle modified to have a distal opening. During open brain surgery, a 2.36-mm probe was used. Each series corresponds to a separate histologic fragment. RESULTS: The diagnoses of the lesions were glioblastoma (4 cases), low-grade glioma (2), grade III oligoastrocytoma (2), and lymphoma (1). Autofluorescence of neurons in cortex was observed. Cellvizio images enabled differentiation of healthy “normal” tissue from pathological tissue in open surgery and stereotactic biopsy using fluorescein. 5-Aminolevulinic acid confocal patterns were difficult to establish. No intraoperative complications related to pCLE or to use of either contrast agent were observed. CONCLUSION: We report the initial feasibility and safety of intraoperative pCLE during primary brain tumor resection and stereotactic biopsy procedures. Pending further investigation, pCLE of brain tissue could be utilized for intraoperative surgical guidance, improvement in brain biopsy yield, and optimization of glioma resection via analysis of tumor margins.

Volume of residual disease as a predictor of outcome in adult patients with recurrent supratentorial glioblastomas multiforme who are undergoing chemotherapy

2004 ◽  
Vol 100 (1) ◽  
pp. 41-46 ◽  
Author(s):  
G. Evren Keles ◽  
Kathleen R. Lamborn ◽  
Susan M. Chang ◽  
Michael D. Prados ◽  
Mitchel S. Berger
Keyword(s):  
Survival Rate ◽  
Residual Disease ◽  
Prognostic Significance ◽  
Tumor Resection ◽  
Progression Free Survival ◽  
Residual Tumor ◽  
Adult Patients ◽  
Content Type ◽  
Response To Chemotherapy ◽  
Fine Print

Object. For patients with recurrent glioblastomas multiforme (GBMs) the prognosis is poor. Although chemotherapy may provide a survival advantage, the role of the extent of tumor resection, or the volume of the residual tumor at the time of recurrence, before instituting chemotherapy, is unclear. This study was designed to assess the response to chemotherapy based on the volume of residual disease (VRD) at the start of treatment in patients with recurrent GBMs. To accomplish this, the authors evaluated a homogeneous group of patients with recurrent GBMs who received the same chemotherapeutic agent. Methods. One hundred nineteen adult patients with recurrent supratentorial GBMs received temozolomide chemotherapy at the time of tumor recurrence. In this cohort the authors analyzed the prognostic significance of volumetrically assessed tumor mass on time to tumor progression (TTP) and survival time (ST). Multivariate analysis demonstrated that the VRD at the beginning of chemotherapy was a statistically significant predictor of both TTP (p < 0.0001) and ST (p < 0.006) when adjusted for the patient's age, performance score, and time from the initial diagnosis. Patients in whom the VRD was less than 10 cm3 at the start of chemotherapy had a 6-month progression-free survival rate of 32% compared with 8% for patients with a VRD between 10 and 15 cm3 and 3% for patients with a VRD larger than 15 cm3. Patients in whom the VRD was smaller than 10 cm3 had a 1-year survival rate of 37% compared with 9% for patients with a VRD between 10 and 15 cm3 and 18% for patients with a VRD larger than 15 cm3. Conclusions. These data indicate that patients with recurrent GBMs who start chemotherapy with a smaller volume (< 10 cm3) of residual disease may have a more favorable response to chemotherapy and a more favorable outcome.

Correlation Between the Residual Tumor Volume, Extent of Tumor Resection, and O6-Methylguanine DNA Methyltransferase Status in Patients with Glioblastoma

2018 ◽  
Vol 116 ◽  
pp. e147-e161 ◽  
Author(s):  
Mayur Sharma ◽  
Sushma Bellamkonda ◽  
Suryanarayan Mohapatra ◽  
Antonio Meola ◽  
Xuefei Jia ◽  
...  
Keyword(s):  
Dna Methyltransferase ◽  
Tumor Volume ◽  
Tumor Resection ◽  
Residual Tumor ◽  
Methylguanine Dna Methyltransferase

Second-line chemotherapy with cabzitaxel and prednisolone (CP) in castratation-resistant prostate cancer (CRPC): Tolerability and efficacy—A U.K. institution experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15128-e15128
Author(s):  
Amir H Montazeri ◽  
Chinnamani Eswarvee ◽  
Helen Wong ◽  
Zafar I Malik
Keyword(s):  
Clinical Outcome ◽  
Symptom Relief ◽  
Case Series ◽  
Progression Free Survival ◽  
Response Rates ◽  
Outcome Data ◽  
Retrospective Case ◽  
First Case ◽  
Docetaxel Treatment ◽  
Retrospective Case Study

e15128 Background: There are limited options for CRPC patients post docetaxel treatment. The majority of these patients have advanced disease with bone metastasis and often have reduced marrow reserve. Cabazitaxel is a novel taxane with activity in docetaxel-resistant/ sensitive cancers with proven clinical benefit in a phase 3 trial. Concerns have been expressed about efficacy and toxicity of this agent in a non trial population. Methods: In this retrospective case study, patients with CRPC treated with CP between Jan-Dec 2011 were included. Response rates (PSA, ALP, radiological) and toxicities (CTCAE) were recorded. All statistical analysis was performed using SPSS v18. Results: 22 men received CP with pegfilgrastim. 41% completed at least 6 cycles of CP and 23% completed 10 cycles. 27% had radiological partial response (RECIST). 36% of patients had ≥50% reduction in PSA level and 61% of patients with elevated ALP had ≥50% reduction. Median follow up was 7.9 months. Progression was defined as clinical, PSA or radiological. 3 patients discontinued treatment because of abnormal LFTs and a further 5 patients for toxicities summarised below. Conclusions: Response rates (RR) in our series (RECIST 27% & PSA 36%) compared favourably with those in the TROPIC trial (14% & 39% respectively) and support CP as an effective and well tolerated option in CRPC. An intriguing finding was the significant RR in ALP level with CP. This may reflect bone penetration of this agent and may correlate with symptom relief and improved clinical outcome. Further prospective studies are needed to investigate this marker with clinical outcome. Data for time to progression, progression free survival and overall survival is immature at this stage and will be updated for the meeting. To our knowledge this is the first case series of patients treated with CP presented outside a clinical trial. [Table: see text]

scholarly journals A modified IRS-III chemotherapy regimen leads to prolonged survival in children with embryonal tumor with multilayer rosettes

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Derek Hanson ◽  
Lindsey M Hoffman ◽  
Sumanth Nagabushan ◽  
Liliana C Goumnerova ◽  
Allison Rathmann ◽  
...  
Keyword(s):  
Patient Outcomes ◽  
Tumor Resection ◽  
Case Series ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Consensus Protocol ◽  
Embryonal Tumor ◽  
International Consensus ◽  
Stem Cell Rescue

Abstract Background Embryonal tumor with multilayer rosettes (ETMR) is a rare CNS malignancy affecting young children that carries a very poor prognosis. Treatment with intensive surgical resection, radiotherapy, and high-dose chemotherapy is insufficient treatment in the vast majority of cases. Effective, biologically based therapies for this tumor are therefore desperately needed. The Dana-Farber Cancer Institute–modified IRS-III protocol incorporates preclinically active agents, such as doxorubicin and actinomycin D, into the treatment regimen for ETMR and may improve patient outcomes. Methods The authors present a case series of 5 children with ETMR treated with an IRS-III-based chemotherapy backbone. Results All 5 patients received a gross-total tumor resection. Patients received between 12 and 51 weeks of IRS-III therapy at the discretion of their treating physician. Four patients received focal radiation therapy, with the fifth patient instead receiving a cycle of high-dose chemotherapy with autologous stem cell rescue. Four patients have progression-free survival of more than 18 months. Chemotherapy treatment was reasonably tolerated by all 5 patients with one case of mild sinusoidal obstructive syndrome and one case of Grade 3 peripheral neuropathy. Conclusions The patient outcomes in this small cohort are far better than would be expected based on the historical survival for this tumor. Given the tremendous need for effective therapy for ETMR, further investigation of this approach is warranted. An international consensus protocol based on the IRS-III regimen has been developed and will be available through a multicenter clinical trial and a global treatment registry.

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