Establishing the Standard of Care for Patients with Newly Diagnosed and Recurrent Glioblastoma

2012 ◽  
pp. 112-117
Author(s):  
Mark R. Gilbert
Keyword(s):  
Signal Transduction ◽  
Tumor Resection ◽  
Standard Of Care ◽  
Recurrent Glioblastoma ◽  
External Beam Radiation ◽  
Standards Of Care ◽  
Successful Implementation ◽  
Newly Diagnosed ◽  
Current Standard ◽  
Beam Radiation

Overview: The current standard of care for patients with newly diagnosed glioblastoma includes maximal safe tumor resection followed by concurrent external-beam radiation with daily low-dose temozolomide followed by 6 to 12 months of adjuvant temozolomide, typically by using a cycle of 5 consecutive days out of 28. Efforts to improve on these results from the European Organisation for Research and Treatment of Cancer (EORTC)/National Cancer Institute of Canada (NCIC) trial using either dose-dense chemotherapy strategies or combinations with signal transduction modulators have, to date, been unsuccessful. Two large international randomized trials examining the efficacy of adding bevacizumab, an antiangiogenic agent, to the standard treatment have been completed, with expectations of results within in the next 2 years. For recurrent glioblastoma, there are no firmly established standards of care. Although intracavitary insertion of carmustine-impregnated polymers has been approved by the U.S. Food and Drug Administration (FDA), this strategy is not widely used. Bevacizumab has been FDA approved for recurrent glioblastoma, but no randomized trial has clearly demonstrated a survival benefit. Alternative dosing schedules of temozolomide (i.e., metronomic) has modest activity even in patients with prior temozolomide exposure. Clinical trials testing small-molecule signal transduction modulators have been disappointing, although most report a small response rate, suggesting that molecularly definable tumor subpopulations may help guide treatment decisions. Successful implementation of marker-based treatment would lead to personalized care and the creation of individualized standards of care.

Regional Therapies for Extremity Sarcoma

2018 ◽  
Author(s):  
Chiara Colombo ◽  
Sandro Pasquali
Keyword(s):  
Local Recurrence ◽  
Local Treatment ◽  
Tumor Resection ◽  
Treatment Strategies ◽  
Soft Tissue Sarcomas ◽  
Isolated Limb Perfusion ◽  
External Beam Radiation ◽  
Resection Margins ◽  
Beam Radiation ◽  
Limb Perfusion

Several regional therapies are used for the local treatment of patients with soft tissue sarcomas (STS), especially for tumors at high risk for local recurrence. Surgery with negative tumor resection margins is the main treatment for primary STS. External-beam radiation therapy is considered for deeply seated, large, and high-grade disease to lower the risk of local recurrence. A combination of preoperative chemo-radiation is associated with improved local control. TNF-α-based isolated limb perfusion is another regional chemotherapy strategy available at specialized surgical oncology units for unresectable STS. Other strategies suitable for management of advanced STS include cryoablation and radiofrequency. This review discusses these and other current regional treatment strategies.  This review contains 10 figures, 6 tables and 64 references Key words: cryoablation, extremity, hyperthermia, isolated limb perfusion, limb infusion, radiotherapy, regional therapy, sarcoma

scholarly journals Evidence-Based Minireview: Should all newly diagnosed MM patients receive CD38 antibody–based treatment?

Hematology ◽  
2020 ◽  
Vol 2020 (1) ◽  
pp. 259-263
Author(s):  
Charlotte L. B. M. Korst ◽  
Niels W. C. J. van de Donk
Keyword(s):  
Progression Free Survival ◽  
Standard Of Care ◽  
Standards Of Care ◽  
Newly Diagnosed ◽  
Phase 3 ◽  
Free Survival ◽  
Depth Of Response ◽  
Cytogenetic Aberrations ◽  
Number Of Patients ◽  
Pretreated Patients

Abstract CD38 antibodies were first evaluated in extensively pretreated patients with multiple myeloma (MM). Currently, there are 3 CD38 antibody–based regimens approved for the treatment of both transplant-eligible (daratumumab plus bortezomib-thalidomide-dexamethasone [D-VTd]) and transplant-ineligible (daratumumab plus lenalidomide-dexamethasone [D-Rd] or daratumumab plus bortezomib-melphalan-prednisone [D-VMP]) patients with newly diagnosed MM (NDMM). The phase 3 studies that evaluated these regimens uniformly showed that the addition of daratumumab to backbone regimens improved the depth of response, which translated into improved progression-free survival and also overall survival in 2 of the studies. Importantly, elderly patients age 75 years or older benefit from these regimens, indicating that these regimens have an acceptable safety profile. Although the number of patients with high-risk cytogenetics was relatively small, these patients also experienced benefit from the addition of daratumumab to standard-of-care regimens, but poor risk conferred by the cytogenetic aberrations is not completely abrogated. Altogether, daratumumab-based regimens have high anti-MM activity and a favorable toxicity profile and therefore represent new standards of care for patients with NDMM.

Future Directions in Glioblastoma Therapy

2012 ◽  
pp. 108-111 ◽  
Author(s):  
Howard Colman
Keyword(s):  
Large Scale ◽  
Antiangiogenic Therapy ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Recurrent Glioblastoma ◽  
The Cancer Genome Atlas ◽  
Antiangiogenic Agents ◽  
Molecular Heterogeneity ◽  
Newly Diagnosed ◽  
Tumor Subtypes

Overview: The standard of care for both newly diagnosed and recurrent glioblastoma (GBM) patients has changed significantly in the past 10 years. Surgery followed by radiation and concurrent and adjuvant temozolomide is now the well-established standard treatment for newly diagnosed GBM. More recently, bevacizumab has become a mainstay of treatment for recurrent GBM. However, despite these advances and significant improvements in patient outcomes, the management and treatment of GBM patients remains a challenging and frustrating endeavor. Difficulties in interpretation of imaging changes after initial treatment, as well as the effects of antiangiogenic agents like bevacizumab on MRI characteristics, can make even the determination of disease progression complicated in multiple situations. Although a high percentage of patients benefit from antiangiogenic therapy in terms of radiographic response and progression-free survival, the effects of bevacizumab on prolonging overall survival remain controversial. Furthermore, tumor progression after treatment with antiangiogenic agents carries a particularly poor prognosis and there is a general lack of effective therapies for this group of patients. These limitations in terms of standard treatments contrast with a relative wealth of new information regarding the molecular underpinnings of GBM. Data from several large-scale efforts to molecularly profile GBM tumors including The Cancer Genome Atlas (TCGA) project have helped define specific molecular subtypes of GBM with distinct biology and clinical outcomes. These findings are helping to refine our understanding of the molecular heterogeneity and pathogenesis of these tumors and provide a basis for the future development of rational and targeted therapies for specific tumor subtypes.

A phase II study of chemoradiation followed by adjuvant temozolomide and poly-ICLC in patients with newly diagnosed glioblastoma: 12- and 18-month survival data (NABTT 0501)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2002-2002
Author(s):  
M. R. Rosenfeld ◽  
M. Chamberlain ◽  
S. A. Grossman ◽  
D. M. Peereboom ◽  
G. J. Lesser ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adjuvant Treatment ◽  
Survival Data ◽  
Cell Activation ◽  
Killer Cell ◽  
External Beam Radiation ◽  
Newly Diagnosed ◽  
Beam Radiation ◽  
Entire Cohort ◽  
Newly Diagnosed Glioblastoma

2002 Background: Polyinosinic-polycytidylic (poly-ICLC), is a double-stranded RNA that stimulates a variety of host defense mechanisms including T-cell and natural killer cell activation, cytokine release and specific anti-proliferative and anti-viral effects. The objective of this study was to determine the safety and efficacy of poly-ICLC when added to adjuvant treatment for newly diagnosed glioblastoma. Methods: Newly diagnosed patients > 18 years with histologically proven glioblastoma received standard external beam radiation with concurrent low-dose temozolomide (TMZ) (75 mg/m2) followed by adjuvant cycles of TMZ for 5 days (150–200 mg/m2) (week 1) then intramuscular injections of poly-ICLC (20 mcg/kg) 3 times a week (weeks 2–8; total 21 injections) with week 9 off and no limit to the number of adjuvant cycles (TMZ + poly-ICLC). Imaging evaluations were performed before every cycle. Results: There were 97 patients enrolled (60 men); median age 56 yrs (range 21–85); median KPS 90 (range 60–100). Fourteen patients did not start adjuvant treatment (5 patient request and 4 investigator withdrawal; 2 progressive disease; 1 death; 1 toxicity; 1 other). The most frequent CTC grade 3–4 toxicities occurring in > 5% of subjects at least possibly related to poly-ICLC were leukopenia (20%), thrombocytopenia (14%), anemia (13%), neutropenia (10%), and SGPT (9%) or alkaline phosphatase (7%) elevation. Two deaths during adjuvant treatment were considered unlikely related to poly-ICLC. To date 71 of 97 patients have survived at least 12 months from diagnosis. The estimated median survival for the entire cohort was 17.2 months (95% CI: 15.5–19.3 months). Overall survival for the cohort at 12 months was 73.2% (95% CI: 63%-82%) and at 18 months 47.4% (95% CI: 37–58%). For only those subjects 18–70 years, overall survival at 18 months was 51.8% (95% CI: 41–63%). This is contrasted with EORTC 26981/22981 that reported an 18 month overall survival of 39.4% (95% CI: 33.8–45.1). Conclusions: The addition of poly-ICLC to a modified adjuvant treatment regimen for newly diagnosed GB is well-tolerated. Survival data at 12 and 18 months suggest increased efficacy compared to chemoradiation with adjuvant TMZ only. [Table: see text]

Disease-specific survival outcomes in lymph node–positive patients with prostate cancer treated with radiotherapy.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 182-182 ◽  
Author(s):  
G. Crehange ◽  
V. K. Weinberg ◽  
A. Izaguirre ◽  
C. C. Hsu ◽  
I. J. Hsu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Disease Free Survival ◽  
External Beam Radiation ◽  
Survival Outcomes ◽  
Primary Therapy ◽  
Newly Diagnosed ◽  
Beam Radiation ◽  
Androgen Ablation ◽  
Disease Free

182 Background: Involvement of regional lymph nodes (LN+) at the time of prostate cancer (PCa) diagnosis is widely regarded as an adverse prognostic factor associated with poor outcome. No commonly utilized treatment, composed of any combination of androgen ablation, surgery and radiation, has proven to be superior for survival. This study will evaluate the clinical survival outcomes of patients (pts) with newly diagnosed LN+ PCa at the University of California San Francisco (UCSF). Methods: All newly diagnosed LN+ PCa pts treated with External Beam Radiation Therapy (EBRT) as primary therapy or after surgery, each with and without androgen ablation between 1987 and 2009 were included. All pts had confirmed pathologic or radiologic LN+ whereas none had evidence of metastases on the work up. Cause Specific Survival (CSS), Disease Free survival (DFS) and biochemical control were measured from the start of treatment. PSA failure was determined by the Phoenix definition after EBRT and by a confirmed PSA >1 ng/mL following RP+EBRT. Results: A retrospective analysis identified 91 pts with LN+ at the time of diagnosis (75.8% high risk pts) with disease follow-up. Thirty-four (37%) were managed with exclusive EBRT alone (eRT), 18 pts (20%) with a combination of radical prostatectomy (RP) and adjuvant EBRT (RP+aRT) and 39 pts (43%) were treated with a combination of RP + salvage RT (RP+sRT). Overall 78% of patients also received hormone therapy (HT): 74.0% with eRT, 89% with RP+aRT and 79% with RP+sRT. The 10 years CSS estimates was 89% for eRT, 0% after RP+aRT and 88% after RP+sRT. The 10 years DFS estimates was 33% for eRT, 0% after RP+aRT and 75% after RP+sRT. Among pts remaining disease free the median follow-up is 38 mos for eRT, 26 mos for RP+aRT and 64 mos for RP+sRT. The last PSA for these patients was <0.1 for 85% of all patients which included 47% following eRT, 100% after RP+aRT and 97% after RP+sRT. There were 7 deaths due to PCa occurring between 5 and 73 mos from the start of EBRT. Conclusions: The results of the current analysis indicate that some pts with LN+ from PCa have prolonged disease free outcomes; and for these men, aggressive treatment may be appropriate. No significant financial relationships to disclose.

Combination chemotherapy versus temozolomide (TMZ) for patients with MGMT methylated (m-MGMT) glioblastoma (GBM): Results of cellworks omics biosimulation—MyCare-015.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e14501-e14501
Author(s):  
Michael Castro ◽  
Nirjhar Mundkur ◽  
Anusha Pampana ◽  
Aftab Alam ◽  
Aktar Alam ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Clinical Decision Making ◽  
Drug Effects ◽  
Standard Of Care ◽  
Clinical Decision ◽  
Phase Iii ◽  
Patient Specific ◽  
Experimental Therapy ◽  
Newly Diagnosed ◽  
Current Standard

e14501 Background: UKT-03 evaluated TMZ plus Lomustine in a single arm phase II trial in newly diagnosed GBM patients. An overall survival of 23 months was a substantial improvement over historical experience. Patients with m-MGMT v. unmethylated tumors had a 2-yr survival of 75% and median survival not reached compared to 20% and 12.5 months, respectively. These data formed the basis for NOA-9, a randomized phase III trial in newly diagnosed, m-MGMT GBM which randomized 141 patients to standard therapy or experimental therapy with Lomustine and TMZ every 6 weeks. A superiority for the combination was observed: 48.1 v. 31.4 months for the standard arm in the ITT analysis. Nevertheless, many neurooncologists are reluctant to adopt this approach. The current standard of care uses single biomarker, m-MGMT, in contrast to comprehensive pathway analysis (CPA). We sought to determine if CPA could discriminate more effectively among each patient’s likelihood of benefiting from combination treatment. Methods: Cellworks Singula employs a novel Cellworks Omics Biology Model (CBM) to predict patient-specific biomarker and phenotype response of personalized GBM avatars to drug agents, radiation, and targeted therapies. The CBM was developed and validated using PubMed to generate protein network maps of patient-specific activated and inactivated disease pathways. CBM was used to simulate the TMZ and TMZ-Lomustine therapies for each patient in a TCGA cohort of 368 GBM patients. Omics data including methylation, whole exome sequencing, and copy number alterations were input into CBM. The Singula Composite Inhibition Score (CIS) was calculated based on the measured quantitative drug effects. Results: Though incremental gain from the combination was seen in all patients, CIS varied across the population with relative scores ranging from 32-82, with best responders have more than twice the benefit. Conclusions: CPA shows that m-MGMT is an excellent biomarker for determining the likelihood of benefit from TMZ and lomustine, with the caveat that CBM identifies 18% could be spared from TMZ exposure and would benefit from Lomustine alone. Otherwise, these data lend support for evolving the standard of care with combination therapy for patients with m-MGMT GBM and should help overcome a reluctance to employing combination therapy. Additionally, CBM has utility to individualize clinical decision making. [Table: see text]

scholarly journals Olfactory Neuroblastoma Treated by Endoscopic Surgery Followed by Combined External Beam Radiation and Gamma Knife for Optic Nerve and Chiasm Sparing: A Case Report

2011 ◽  
Vol 2011 ◽  
pp. 1-3 ◽  
Author(s):  
Hansi Z. Jiang ◽  
Ameer L. Elaimy ◽  
Guy C. Jones ◽  
Alexander R. Mackay ◽  
Robert K. Fairbanks ◽  
...  
Keyword(s):  
Endoscopic Surgery ◽  
External Beam Radiotherapy ◽  
Tumor Resection ◽  
Multimodality Treatment ◽  
Olfactory Neuroblastoma ◽  
Concurrent Chemotherapy ◽  
External Beam Radiation ◽  
External Beam ◽  
Beam Radiation ◽  
The Right

We describe the multimodality treatment regimen of a 53-year-old man diagnosed with olfactory neuroblastoma (Kadish stage C) in the right nasal cavity extending into the ethmoid sinus and across the cribriform plate. Endoscopic surgery for tumor resection was followed by a combination of external beam radiotherapy and stereotactic radiosurgery boost with concurrent chemotherapy. The novel combination of dual radiation therapies allowed for the preservation of the nearby optic structures while providing an adequate dosage to a sufficient volume of the afflicted tissue.

Resection, biopsy, and survival in malignant glial neoplasms

1993 ◽  
Vol 78 (5) ◽  
pp. 767-775 ◽  
Author(s):  
Bertrand C. Devaux ◽  
Judith R. O'Fallon ◽  
Patrick J. Kelly
Keyword(s):  
Radiation Therapy ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Tumor Resection ◽  
External Beam Radiation ◽  
Newly Diagnosed ◽  
Content Type ◽  
Grade Iii ◽  
Fine Print

✓ Between July, 1984, and October, 1988, 263 patients (163 male, 100 female), aged from 4 to 83 years (mean 52 years), with malignant brain gliomas underwent surgical procedures: stereotactic biopsy in 160 and resection in 103 patients. There were 170 grade IV astrocytomas, 17 grade IV mixed oligoastrocytomas, 44 grade III astrocytomas, 22 grade III mixed oligoastrocytomas, and 10 malignant oligodendrogliomas. Overall median survival time was 30.1 weeks for grade IV gliomas, 87.7 weeks for grade III gliomas, and 171.3 weeks for malignant oligodendrogliomas. Multivariate analysis in 218 newly diagnosed cases revealed that the variables most strongly correlated with survival time were: tumor grade, patient age, seizures as a first symptom, a Karnofsky Performance Scale score of less than 70%, tumor resection, and a radiation therapy dose greater than 50 Gy. The proportions of patients receiving tumor resection versus biopsy in each of these prognosis factor groups were similar. Since most of the 22 patients with midline and brain-stem tumors were treated with biopsy alone, these were excluded. Considering 196 newly diagnosed patients with cortical and subcortical tumors, grade IV glioma patients undergoing resection of the contrast-enhancing mass (as evidenced on computerized tomography and magnetic resonance imaging) and postoperative external beam radiation therapy lived longer than those undergoing biopsy only and radiation therapy (median survival time 50.6 weeks and 33.0 weeks, respectively; Smirnov test, p = 0.0380). However, survival in patients with resected grade III gliomas was no better than in those with biopsied grade III lesions (p = 0.746). The authors conclude that, in selected grade IV gliomas, resection of the contrast-enhancing mass followed by radiation therapy is associated with longer survival times than radiation therapy after biopsy alone.

scholarly journals Sedation and Anesthesia Options for Pediatric Patients in the Radiation Oncology Suite

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Eric A. Harris
Keyword(s):  
Radiation Oncology ◽  
Patient Monitoring ◽  
Pediatric Patients ◽  
Review Paper ◽  
External Beam Radiation Therapy ◽  
External Beam Radiation ◽  
Standards Of Care ◽  
External Beam ◽  
Beam Radiation ◽  
Pediatric Sedation

External beam radiation therapy (XRT) has become one of the cornerstones in the management of pediatric oncology cases. While the procedure itself is painless, the anxiety it causes may necessitate the provision of sedation or anesthesia for the patient. This review paper will briefly review the XRT procedure itself so that the anesthesia provider has an understanding of what is occurring during the simulation and treatment phases. We will then examine several currently used regimens for the provision of pediatric sedation in the XRT suite as well as a discussion of when and how general anesthesia should be performed if deemed necessary. Standards of care with respect to patient monitoring will be addressed. We will conclude with a survey of the developing field of radiation-based therapy administered outside of the XRT suite.

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