scholarly journals Rationale and Clinical Implications of Fluorescein-Guided Supramarginal Resection in Newly Diagnosed High-Grade Glioma

2021 ◽  
Vol 11 ◽  
Author(s):  
Linda M. Wang ◽  
Matei A. Banu ◽  
Peter Canoll ◽  
Jeffrey N. Bruce
Keyword(s):  
Overall Survival ◽  
Surgical Resection ◽  
Local Treatment ◽  
Standard Of Care ◽  
High Grade Glioma ◽  
Extent Of Resection ◽  
Brain Parenchyma ◽  
Clinical Implications ◽  
Current Standard ◽  
Supramarginal Resection

Current standard of care for glioblastoma is surgical resection followed by temozolomide chemotherapy and radiation. Recent studies have demonstrated that >95% extent of resection is associated with better outcomes, including prolonged progression-free and overall survival. The diffusely infiltrative pattern of growth in gliomas results in microscopic extension of tumor cells into surrounding brain parenchyma that makes complete resection unattainable. The historical goal of surgical management has therefore been maximal safe resection, traditionally guided by MRI and defined as removal of all contrast-enhancing tumor. Optimization of surgical resection has led to the concept of supramarginal resection, or removal beyond the contrast-enhancing region on MRI. This strategy of extending the cytoreductive goal targets a tumor region thought to be important in the recurrence or progression of disease as well as resistance to systemic and local treatment. This approach must be balanced against the risk of impacting eloquent regions of brain and causing permanent neurologic deficit, an important factor affecting overall survival. Over the years, fluorescent agents such as fluorescein sodium have been explored as a means of more reliably delineating the boundary between tumor core, tumor-infiltrated brain, and surrounding cortex. Here we examine the rationale behind extending resection into the infiltrative tumor margins, review the current literature surrounding the use of fluorescein in supramarginal resection of gliomas, discuss the experience of our own institution in utilizing fluorescein to maximize glioma extent of resection, and assess the clinical implications of this treatment strategy.

scholarly journals Co-Clinical Trials: An Innovative Drug Development Platform for Cholangiocarcinoma

2021 ◽  
Vol 14 (1) ◽  
pp. 51
Author(s):  
Brinda Balasubramanian ◽  
Simran Venkatraman ◽  
Kyaw Zwar Myint ◽  
Tavan Janvilisri ◽  
Kanokpan Wongprasert ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
Drug Development ◽  
Surgical Resection ◽  
Treatment Options ◽  
Standard Of Care ◽  
Time Data ◽  
Current Standard ◽  
Innovative Drug ◽  
Curative Intent

Cholangiocarcinoma (CCA), a group of malignancies that originate from the biliary tract, is associated with a high mortality rate and a concerning increase in worldwide incidence. In Thailand, where the incidence of CCA is the highest, the socioeconomic burden is severe. Yet, treatment options are limited, with surgical resection being the only form of treatment with curative intent. The current standard-of-care remains adjuvant and palliative chemotherapy which is ineffective in most patients. The overall survival rate is dismal, even after surgical resection and the tumor heterogeneity further complicates treatment. Together, this makes CCA a significant burden in Southeast Asia. For effective management of CCA, treatment must be tailored to each patient, individually, for which an assortment of targeted therapies must be available. Despite the increasing numbers of clinical studies in CCA, targeted therapy drugs rarely get approved for clinical use. In this review, we discuss the shortcomings of the conventional clinical trial process and propose the implementation of a novel concept, co-clinical trials to expedite drug development for CCA patients. In co-clinical trials, the preclinical studies and clinical trials are conducted simultaneously, thus enabling real-time data integration to accurately stratify and customize treatment for patients, individually. Hence, co-clinical trials are expected to improve the outcomes of clinical trials and consequently, encourage the approval of targeted therapy drugs. The increased availability of targeted therapy drugs for treatment is expected to facilitate the application of precision medicine in CCA.

A Direct Comparison of High Dose Cytarabine to Combination of Gemtuzumab and High Dose Cytarabine for Acute Myeloid Leukemia Patients in First Relapse Confirmed the Benefit of Gemtuzumab Based Regimens.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2051-2051
Author(s):  
Thomas Prébet ◽  
Aude Charbonnier ◽  
Anne Etienne ◽  
Evelyne D'Incan ◽  
Sabine Fürst ◽  
...  
Keyword(s):  
Overall Survival ◽  
Response Rate ◽  
Standard Of Care ◽  
Allogeneic Transplantation ◽  
Control Group ◽  
High Dose ◽  
Current Standard ◽  
Advanced Phase ◽  
High Dose Cytarabine ◽  
First Relapse

Abstract Abstract 2051 Poster Board II-28 Acute meyloid leukemia (AML) in first relapse is associated with a poor outcome when treated with standard dose cytarabine regimens and intermediate to high dose cytarabine (IHDAraC) is the current standard of care. During the last years, Gemtuzumab Ozogamycin (GO) has demonstrated a relevant clinical activity in relapsed and refractory AML. This antibody directed against CD33 is conjugated to calicheamycin that triggers apoptosis when hydrolyzed in the leukemic blasts. Combination regimen of GO are currently extensively studied in both frontline and advanced phase disease. Nevertheless, analysis of the litterature showed that only few data are available regarding a direct comparison of IHDAraC and IHDAraC+GO regimen. To this respect, we conduced a retrospective analysis of response (CR and CRi) and survival for patients with first relapse AML treated in our centre with either IHDAraC or IHDAraC+GO regimen. A total of 84 patients were included in the analysis: 28 were induced in the IHDAraC+GO group (mean GO dose: 6mg/m2, range:[3-9], including 82% of combination with anthracyclines or etoposide) and 56 in the IHDAraC group (including 57% of combination with other agents, mostly etoposide and anthracyclines). Patients characteristics were comparable between the IHDAraC+GO group and the control group in terms of median age (51y vs 49y), Performance Status at relapse (1 vs 1), median time to relapse (221 days vs 280 days), cytogenetic risk group clustering and previous allogeneic transplantation in first CR (21% vs 16%). Median Follow-up was 24 months. Univariate analysis showed that IHDAraC+GO induction, as compared with IHDAraC, was associated with a better response rate (68% vs 48%, p=0.08), a lower relapse rate (31% vs 66%, p=0.02), a better Overall Survival (median 35 months vs 19 months, p=0.02) and a better Event Free Survival (median Not Reached vs 10 months, p=0.02). Of note, the better response rate in the IHDAraC+GO group allowed to bring more patients to allogeneic transplantation in second CR (33% vs 16% respectively, p=0.08).Multivariate analysis using logistic regression method for response evaluation and Cox model for survival showed that treatment in the IHDAraC+GO group was an independent prognosis factor with a favorable impact on both response (HR:2.8, 95%CI:[1.1-7.7], p=0.048) and Overall Survival (HR:1.9, 95%CI:[1.1-3.4], p=0.047). It is already known that combination of IHDAraC and GO could give good results for advanced phase AML patients but, to our knowledge, this report is the first that directly compared the results of IHDAraC+GO with the current standard of care regimen on an homogeneous sample of patients in first relapse. This report also underline the importance of a prospective comparison in order to define the best combination therapy. Disclosures: No relevant conflicts of interest to declare.

scholarly journals A Review of Newly Diagnosed Glioblastoma

2021 ◽  
Vol 10 ◽  
Author(s):  
Bryan Oronsky ◽  
Tony R. Reid ◽  
Arnold Oronsky ◽  
Navjot Sandhu ◽  
Susan J. Knox
Keyword(s):  
Brain Tumor ◽  
Surgical Resection ◽  
Standard Of Care ◽  
Newly Diagnosed ◽  
Current Standard ◽  
Genetic Characteristics ◽  
Dismal Prognosis ◽  
Newly Diagnosed Glioblastoma ◽  
Temozolomide Chemotherapy

Glioblastoma is an aggressive and inevitably recurrent primary intra-axial brain tumor with a dismal prognosis. The current mainstay of treatment involves maximally safe surgical resection followed by radiotherapy over a 6-week period with concomitant temozolomide chemotherapy followed by temozolomide maintenance. This review provides a summary of the epidemiological, clinical, histologic and genetic characteristics of newly diagnosed disease as well as the current standard of care and potential future therapeutic prospects.

scholarly journals RARE-09. CYSTIC GLIOBLASTOMA PRESENTATION AS A BENEFICIAL PROGNOSTIC INDICATOR FOR OVERALL SURVIVAL

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi223-vi223
Author(s):  
Lee Curtin ◽  
Paula Whitmire ◽  
Cassandra Rickertsen ◽  
Peter D Canoll ◽  
Maciej Mrugala ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Benefit ◽  
Standard Of Care ◽  
Prognostic Impact ◽  
Current Standard ◽  
Significant Survival Benefit ◽  
Care Treatment ◽  
Significant Survival ◽  
Cystic Component ◽  
Standard Of Care Treatment

Abstract Glioblastoma (GBM) is the most aggressive primary brain tumor with a median overall survival of 15 months with standard-of-care treatment. GBM patients sometimes present with a cystic component, which can be identified through magnetic resonance imaging (MRI). Previous studies suggest that cysts occur in 7–22% of GBM patients and have reported mixed results regarding whether cystic GBM have a survival benefit compared to noncystic GBM. Using our large retrospective cohort of 493 first-diagnosis GBM patients, we aim to elucidate this link between cystic GBM and survival. Within this cohort, 88 patients had a significant cystic component at presentation as identified on MRI. Compared to noncystic GBM (n=405), cystic GBM patients had significantly better overall survival (15 vs 22 months median, log-rank, p=0.001) and were significantly younger at the time of presentation (t-test, p=0.002). However, within patients that received current standard-of-care treatment (n=184), cystic GBM (n=40) was not as beneficial for outcome (22 vs 25 months, log-rank, p=0.3). We also did not observe a significant survival benefit when comparing this standard-of-care cystic cohort to cystic GBM patients diagnosed before the standard was established (n=19, 25 vs 23 months, log-rank, p=0.3), but the analogous result for noncystic GBM patients gives a sizeable benefit, as expected (n=144, n=111, respectively, 22 vs 12 months, log-rank p < 0.0001). Together, these results on current standard-of-care may explain later studies that note no significant survival benefit for cystic GBM patients receiving current standard-of-care. We also report differences in the absolute and relative sizes of imaging abnormalities on MRI and in prognostic impact of cysts based on sex. We discuss current hypotheses for these observed differences, including the possibility that the presence of a cyst could be indicative of a less aggressive tumor.

Survival improvement by systemic chemotherapy in adult patients with recurrent glioblastoma multiforme treated with two courses of radiotherapy

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1578-1578
Author(s):  
C. Nieder ◽  
A. L. Grosu ◽  
S. Astner ◽  
N. Andratschke ◽  
M. Molls
Keyword(s):  
Overall Survival ◽  
Glioblastoma Multiforme ◽  
Surgical Resection ◽  
Cumulative Dose ◽  
Systemic Chemotherapy ◽  
Local Treatment ◽  
Adult Patients ◽  
External Beam ◽  
Median Cumulative Dose ◽  
First Diagnosis

1578 Background: We evaluated the added value of systemic chemotherapy (CTx) in adult patients with recurrent supratentorial glioblastoma multiforme (GBM) selected to receive local re-treatment (administered as a 2nd course of radiotherapy, RTx). Methods: Retrospective comparison of two patient cohorts treated subsequently during different time periods. All patients had histologically confirmed recurrent GBM. Minimum recurrence-free interval was 4 months. The first cohort (n=26) had surgical resection and standard postoperative external beam RTx followed by a second course of external beam RTx for recurrence (median cumulative dose 102 Gy). None of these patients ever received CTx during the whole course of disease. The more recently treated cohort (after 1999) of 19 patients also had surgical resection and 2 courses of external beam RTx (median cumulative dose 90 Gy). After primary local treatment, 9 of these patients had adjuvant nitrosourea-based CTx. At recurrence, all 19 patients received temozolomide 150–200 mg/m2/day for five days every 4 weeks in addition to RTx. Results: The cohort without CTx had less favorable baseline characteristics, because of their significantly lower median KPS at recurrence (70 vs. 90%, p<0.01) and shorter interval between primary diagnosis and recurrence (12 vs. 16 months, p<0.05). However, these patients were non-significantly younger (median age 44 vs. 50 years, p>0.05). The percentage of patients with secondary GBM was similar (21 vs. 23%, p>0.5). Median survival from re-irradiation was significantly better in the RTx plus CTx group, 9 vs. 5 months (p<0.05). In multivariate analysis, prognosis was significantly improved by CTx. Importantly, there was also an advantage when overall survival from first diagnosis was evaluated, median 24 vs. 19 months (p<0.05). Conclusion: The current data suggest that re-irradiation plus temozolomide is better than re-irradiation alone. CTx led to a prolongation of overall survival from first diagnosis by 5 months. The most intensively treated, prognostically favourable de-novo GBM patients had surgical resection, 2 courses of RTx and 2 different systemic CTx regimens. [Table: see text]

Posterior Fossa Ependymoma

2019 ◽  
pp. 223-230
Author(s):  
Frederick A. Boop ◽  
Jimmy Ming-Jung Chuang
Keyword(s):  
Posterior Fossa ◽  
Fourth Ventricle ◽  
Obstructive Hydrocephalus ◽  
Standard Of Care ◽  
Extent Of Resection ◽  
Clinical Findings ◽  
Current Standard ◽  
Subarachnoid Spaces ◽  
Growth Of Tumor ◽  
Foramen Of Luschka

Pediatric posterior fossa ependymomas are typically well-delineated masses with heterogenous enhancement arising from the floor, lateral aspect, or roof of the fourth ventricle. Growth of tumor into the posterior fossa subarachnoid spaces, particularly into the foramen of Magendie and the cerebellopontine angles via the foramen of Luschka, is a radiological hallmark of this tumor. Clinical findings of elevated intracranial pressure and obstructive hydrocephalus are common at presentation. The current standard of care for children with ependymoma consists of gross total resection with subsequent focal radiotherapy. The extent of resection is the single most important determinant of outcome. Hydrocephalus typically resolves after resection, and it is uncommon to require cerebrospinal shunt placement after tumor removal.

scholarly journals 20 Disparities in survival for patients with glioblastoma multiforme

2018 ◽  
Vol 45 (S3) ◽  
pp. S4-S4
Author(s):  
Mostafa Fatehi ◽  
Camille Hunt ◽  
Roy Ma ◽  
Brian Toyota
Keyword(s):  
British Columbia ◽  
Overall Survival ◽  
Glioblastoma Multiforme ◽  
Median Overall Survival ◽  
Performance Status ◽  
Treatment Strategies ◽  
Standard Of Care ◽  
Extent Of Resection ◽  
Pathologic Classification ◽  
Genetic Features

Background: Glioblastoma multiforme (GBM) is the most common malignant primary brain cancer in adults. Recent efforts have elucidated genetic features of tumor cells and thus enhanced our knowledge of GBM pathophysiology. The most recent clinical trials report median overall survival between 14 and 20 months. However, real-world outcomes are quite variable and there is a paucity of data within the literature. Methods: Three hundred seventy two GBM patients were diagnosed in the province of British Columbia between January 2013 and January 2015. We have performed a retrospective review on the survival outcomes of the 278 patients who underwent surgical resection as part of the initial treatment. Results: Our results indicate a median age of 61.8y at time of diagnosis with a slight preponderance of males. The median overall survival was 10 months for patients who underwent surgery. As expected, patients over the age of 65 and those with worse initial Karnofsy Performance Status (KPS) scores had a poorer prognosis. Moreover, we have found extent of resection (EOR), treatment strategies and treatment location affect overall survival. Conclusion: The present study highlights factors which affect patient survival after surgery in British Columbia. Our outcomes are slightly worse than survival reported in the US. Variability in pathologic classification and in treatment strategy likely contribute to this difference. Further efforts should ensure access to the gold-standard of care.

scholarly journals Is local radiotherapy a viable option for patients with an opening of the ventricles during surgical resection of brain metastases?

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Sophia Scharl ◽  
Kerstin A. Kessel ◽  
Christian Diehl ◽  
Jens Gempt ◽  
Bernhard Meyer ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Surgical Resection ◽  
Local Treatment ◽  
Whole Brain Radiotherapy ◽  
Standard Of Care ◽  
Neurological Impairment ◽  
Distant Recurrence ◽  
Tumor Bed ◽  
Resection Cavity ◽  
Brain Radiotherapy

Abstract Background Local hypofractionated stereotactic radiotherapy (HFSRT) of the resection cavity is emerging as the standard of care in the treatment of patients with a limited number of brain metastases as it warrants less neurological impairment compared to whole brain radiotherapy. In periventricular metastases surgical resection can lead to an opening of the ventricles and subsequently carries a potential risk of cerebrospinal tumour cell dissemination. The aim of this study was to assess whether local radiotherapy of the resection cavity is viable in these cases. Methods From our institutional database we analyzed the data of 125 consecutive patients with resected brain metastases treated in our institution with HFSRT between 2009 and 2017. The incidence of LMD, overall survival (OS), local recurrence (LC) and distant recurrence were evaluated depending on ventricular opening (VO) during surgery. Results From all 125 patients, the ventricles were opened during surgery in 14 cases (11.2%). None of the patients with VO and 7 patients without VO during surgery developed LMD (p = 0.371). OS (p = 0.817), LC (p = 0.524) and distant recurrence (p = 0.488) did not differ in relation to VO during surgical resection. However, the incidence of distant intraventricular recurrence was slightly increased in patients with VO (14.3% vs. 2.7%, p < 0.01). Conclusion VO during neurosurgical resection did not affect the outcome after HFSRT of the resection cavity in patients with brain metastases. Particularly, the incidence of LMD was not increased in patients receiving local HFSRT after VO. HFSRT can therefore be offered independently of VO as a local treatment of tumor bed after resection of brain metastases.

scholarly journals Glioblastoma in the elderly: the effect of aggressive and modern therapies on survival

2016 ◽  
Vol 124 (4) ◽  
pp. 998-1007 ◽  
Author(s):  
Ranjith Babu ◽  
Jordan M. Komisarow ◽  
Vijay J. Agarwal ◽  
Shervin Rahimpour ◽  
Akshita Iyer ◽  
...  
Keyword(s):  
Overall Survival ◽  
Elderly Patients ◽  
Median Survival ◽  
Standard Of Care ◽  
Extent Of Resection ◽  
Older Age ◽  
Karnofsky Performance Scale ◽  
Subtotal Resection ◽  
Newly Diagnosed ◽  
Complication Risk

OBJECT The prognosis of elderly patients with glioblastoma (GBM) is universally poor. Currently, few studies have examined postoperative outcomes and the effects of various modern therapies such as bevacizumab on survival in this patient population. In this study, the authors evaluated the effects of various factors on overall survival in a cohort of elderly patients with newly diagnosed GBM. METHODS A retrospective review was performed of elderly patients (≥ 65 years old) with newly diagnosed GBM treated between 2004 and 2010. Various characteristics were evaluated in univariate and multivariate stepwise models to examine their effects on complication risk and overall survival. RESULTS A total of 120 patients were included in the study. The median age was 71 years, and sex was distributed evenly. Patients had a median Karnofsky Performance Scale (KPS) score of 80 and a median of 2 neurological symptoms on presentation. The majority (53.3%) of the patients did not have any comorbidities. Tumors most frequently (43.3%) involved the temporal lobe, followed by the parietal (35.8%), frontal (32.5%), and occipital (15.8%) regions. The majority (57.5%) of the tumors involved eloquent structures. The median tumor size was 4.3 cm. Every patient underwent resection, and 63.3% underwent gross-total resection (GTR). The vast majority (97.3%) of the patients received the postoperative standard of care consisting of radiotherapy with concurrent temozolomide. The majority (59.3%) of patients received additional agents, most commonly consisting of bevacizumab (38.9%). The median survival for all patients was 12.0 months; 26.7% of patients experienced long-term (≥ 2-year) survival. The extent of resection was seen to significantly affect overall survival; patients who underwent GTR had a median survival of 14.1 months, whereas those who underwent subtotal resection had a survival of 9.6 months (p = 0.038). Examination of chemotherapeutic effects revealed that the use of bevacizumab compared with no bevacizumab (20.1 vs 7.9 months, respectively; p < 0.0001) and irinotecan compared with no irinotecan (18.0 vs 9.7 months, respectively; p = 0.027) significantly improved survival. Multivariate stepwise analysis revealed that older age (hazard ratio [HR] 1.06 [95% CI1.02–1.10]; p = 0.0077), a higher KPS score (HR 0.97 [95% CI 0.95–0.99]; p = 0.0082), and the use of bevacizumab (HR 0.51 [95% CI 0.31–0.83]; p = 0.0067) to be significantly associated with survival. CONCLUSION This study has demonstrated that GTR confers a modest survival benefit on elderly patients with GBM, suggesting that safe maximal resection is warranted. In addition, bevacizumab significantly increased the overall survival of these elderly patients with GBM; older age and preoperative KPS score also were significant prognostic factors. Although elderly patients with GBM have a poor prognosis, they may experience enhanced survival after the administration of the standard of care and the use of additional chemotherapeutics such as bevacizumab.

scholarly journals NCOG-69. SEX DIFFERENCES IN GLIOBLASTOMA PATIENT SURVIVAL AS A FUNCTION OF EXTENT OF SURGICAL RESECTION AND CYCLES OF ADJUVANT TEMOZOLOMIDE DURING STANDARD-OF-CARE REGIMENS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii144-ii145
Author(s):  
Julia Lorence ◽  
Tomas Bencomo ◽  
Haylye White ◽  
Cassandra Rickertsen ◽  
Susan Massey ◽  
...  
Keyword(s):  
Overall Survival ◽  
Sex Differences ◽  
Brain Tumor ◽  
Surgical Resection ◽  
Patient Survival ◽  
Standard Of Care ◽  
Subtotal Resection ◽  
P Value ◽  
Adjuvant Temozolomide ◽  
Group I

Abstract OBJECTIVE Glioblastoma (GBM) is the most common malignant primary brain tumor in adults, with males more commonly affected than females(1.6:1). Despite advancements in treatments, prognosis is dismal with a median overall survival of 15 months. Our aim was to investigate sex as a variable in GBM patient survival after receiving incremental levels of standard-of-care treatment regimens – different extents of surgical resection and different numbers of cycles of adjuvant temozolomide chemotherapy. METHODS Drawing from our extensive multi-institutional brain tumor repository, we investigated GBM subjects with overall survival (OS), extent of resection (EOR), number of temozolomide (TMZ) cycles, and sex data (n=620, males: n=387, females: n=233). Cox proportional hazard ratios were computed to investigate the multivariable predictive value of the patient variables with OS. Patients were then divided into groups based on their sex, EOR (either biopsy, subtotal resection (STR) or gross total resection (GTR)), and TMZ cycles (I: &lt; 6 cycles, II: 7-11 cycles and III: &gt;12 cycles). RESULTS We observed that STR was beneficial for females (HR=0.52; CI=0.33-0.83; p-value=0.013), while for males the benefit was not detected (HR=0.73; CI=0.46-1.15; p-value=0.173) for STR but was detectable for GTR (HR=0.58, CI=0.37-0.90; p-value=0.014). Females receiving 7-11 cycles of TMZ showed a survival benefit (HR=0.52; CI=0.12-0.53; p-value=0.048) while males in the same group did not (HR=0.74; CI=0.46-1.19; p-value=0.21), in comparison to those in group I of TMZ cycles. No sex differences were identified in patients receiving &lt; =6 cycles or &gt;=12 cycles. CONCLUSION Together, our results contribute to the growing literature that sex differences exist in GBM patients, even in response to standard-of-care therapies. This should be accounted for when designing clinical trials for GBM so that we may advance our pursuit to deliver personalized medicine.

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