Ivosidenib, an IDH1 inhibitor, in a patient with recurrent, IDH1-mutant glioblastoma: a case report from a Phase I study

Glioblastoma is the most common and aggressive primary brain tumor. Despite standard multimodality therapy, median overall survival remains poor with a 5-year survival rate of approximately 5% in most studies (range 4.7–13.0%). Strong interest in targeting IDH mutations has led to a variety of studies in both hematologic malignancies and solid tumors and to the approval of IDH inhibitors such as ivosidenib, an IDH1 inhibitor, in hematologic malignancies. Here, we present the first case study of a patient with a recurrent IDH1-mutant glioblastoma who experienced improved seizure control and radiographic stable disease for more than 4 years while treated with ivosidenib. Such findings support the further development of IDH inhibitors as single agents and/or in combination for the treatment of IDH-mutant glioma.

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Chronic Graft Versus Host Disease and Pretransplant Disease Status Predict Outcomes in Patients with Hematologic Malignancies Undergoing Reduced Intensity Allogeneic Stem Cell Transplantation.

Blood ◽

10.1182/blood.v110.11.5090.5090 ◽

2007 ◽

Vol 110 (11) ◽

pp. 5090-5090

Author(s):

Megha A. Shah ◽

Mounzer Agha ◽

Markus Mapara ◽

Kate Lenhart ◽

Anastasios Raptis

Keyword(s):

Overall Survival ◽

Median Overall Survival ◽

Chronic Gvhd ◽

Disease Free Survival ◽

Disease Status ◽

Hematologic Malignancies ◽

Free Survival ◽

Effective Treatment Modality ◽

Disease Free ◽

Reduced Intensity

Abstract Reduced intensity stem cell transplantation (SCT) is an effective treatment modality for patients with hematologic malignancies who are not candidates for conventional myeloablative SCT. We conducted a retrospective review of all patients with hematologic malignancies receiving a reduced intensity allogeneic SCT from July 2002 to July 2007. Data pertaining to patient demographics, engraftment, disease status pre and post transplant, graft versus host disease (GVHD), and HLA matching was analyzed to identify factors significantly affecting the clinical outcome. Seventy three patients, with a median age of 55 (range of 19–70) and with the diagnoses of ALL (n=8), AML (n=30), CLL (n=3), CML (n=1), Hodgkin’s (n=7), non-Hodgkin’s (n=7), MDS (n=11), and MM (n=6) underwent a reduced intensity SCT using a fludarabine based conditioning regimen. Thirty nine (53%) received unrelated donor grafts and 34 (47%) received sibling donor grafts. Fifty six patients (77%) received fully matched grafts whereas 17 patients (23%) had an antigen or allele mismatch. Acute GVHD grade II-IV was observed in 27 of the 73 patients and chronic GVHD was seen in 18 of the 48 patients who could be evaluated. Seventeen patients developed transplant related fatal complications and 30 patients died from disease progression or relapse. Median time to neutrophil recovery was 15 days (range of 9–41 days) and median time to platelet recovery was 18 days (range of 9–42 days). Graft failure was observed in 6 of the 73 patients. Median overall survival and disease free survival for all patients was 7.7 and 6.6 months respectively. Median overall survival for patients with persistent disease or in remission at the time of the SCT was 5.6 and 21.8 months (p= 0.01) while that for disease free survival was 5.7 and 8.4 months (p=0.06). Median overall survival with and without chronic GVHD was 25.6 and 9.4 months (p <0.0001) while median disease free survival was 18.2 and 6.0 months (p< 0.0001). Patients with limited chronic GVHD have not yet reached median overall survival while the median disease free survival was 18.4 months. Those with no or extensive chronic GVHD had medians of 9.4 and 9.2 months for overall survival and 6.0 and 9.2 months for disease free survival (p= 0.004 and p=0.02). The source of the stem cells as well as the administration of allele or single antigen mismatch grafts did not affect the outcome. Reduced intensity SCT is an effective treatment modality in patients with hematologic malignancies, though it is most effective in patients who are in remission at the time of transplant and should be offered in this setting. Patients with limited chronic GVHD had a better outcome suggesting the presence of potent anti-tumor activity of the donor immune competent cells without the detrimental effects in clinical outcome caused by extensive chronic GVHD.

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Requirements on Dimensions for a Maturity Model for Smart Grids Based on Two Case Studies

10.4018/978-1-6684-3666-0.ch021 ◽

2022 ◽

pp. 443-464

Author(s):

Agnetha Flore ◽

Jorge Marx Goméz

Keyword(s):

Requirements Engineering ◽

Smart Grids ◽

Future Research ◽

Maturity Model ◽

Literature Research ◽

Research Activities ◽

First Case ◽

Agile Approach ◽

Further Development

This contribution describes two different types of requirements engineering analysis of the necessary dimensions of a possible maturity model for Smart Grids to be implemented for utilities. For the first case study, the requirements engineering for necessary dimensions for a Smart Grid maturity model was elicited using a systematic literature research. On the contrary a more agile approach is used for the second requirements engineering. For this more agile approach, interviews with energy suppliers were conducted, taking into account the analysis of the literature research. Various energy suppliers from Germany took part in the survey. The results were used to develop the basic framework for a maturity model for Smart Grids, which can still be tailored if necessary. Finally, future research activities for the application and further development of maturity models for Smart Grids in the energy industry are explained as well as the different procedural variants in the requirements analysis.

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Risk of Hematologic Malignancies After Radioiodine Treatment of Well-Differentiated Thyroid Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2017.75.0232 ◽

2018 ◽

Vol 36 (18) ◽

pp. 1831-1839 ◽

Cited By ~ 39

Author(s):

Remco J. Molenaar ◽

Surbhi Sidana ◽

Tomas Radivoyevitch ◽

Anjali S. Advani ◽

Aaron T. Gerds ◽

...

Keyword(s):

Overall Survival ◽

Thyroid Cancer ◽

Myeloid Leukemia ◽

Differentiated Thyroid Cancer ◽

Median Overall Survival ◽

Hematologic Malignancies ◽

Hazard Ratio ◽

Early Risk ◽

Increased Risk ◽

Well Differentiated

Purpose To investigate the risk and outcomes of second hematologic malignancies (SHMs) in a population-based cohort of patients with well-differentiated thyroid cancer (WDTC) treated or not with radioactive iodine (RAI). Methods Patients with WDTC were identified from SEER registries. Competing risk regression analysis was performed to calculate the risks of SHMs that occurred after WDTC treatment and outcomes after SHM development were assessed. Results Of 148,215 patients with WDTC, 53% received surgery alone and 47% received RAI. In total, 783 patients developed an SHM after a median interval of 6.5 years (interquartile range, 3.3 to 11.2 years) from WDTC diagnosis. In multivariable analysis, compared with those undergoing thyroidectomy alone, RAI treatment was associated with an increased early risk of developing acute myeloid leukemia (AML; hazard ratio, 1.79; 95% CI, 1.13 to 2.82; P = .01) and chronic myeloid leukemia (CML; hazard ratio, 3.44; 95% CI, 1.87 to 6.36; P < .001). This increased risk of AML and CML after RAI treatment was seen even in low-risk and intermediate-risk WDTC tumors. Occurrence of AML but not CML in patients with WDTC was associated with shorter median overall survival compared with matched controls (8.0 years v 31.0 years; P = .001). In addition, AML developing after RAI trended toward inferior survival compared with matched controls with de novo AML (median overall survival, 1.2 years v 2.9 years; P = .06). Conclusion Patients with WDTC treated with RAI had an increased early risk of developing AML and CML but no other hematologic malignancies. AML that arises after RAI treatment has a poor prognosis. RAI use in patients with WDTC should be limited to patients with high-risk disease features, and patients with WDTC treated with adjuvant RAI should be monitored for myeloid malignancies as part of cancer surveillance.

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CN1 Mean Versus Median Overall Survival (OS) For Describing Value of New Cancer Therapies: A Case Study

Value in Health ◽

10.1016/j.jval.2011.08.014 ◽

2011 ◽

Vol 14 (7) ◽

pp. A234

Author(s):

A. Davies ◽

A. Briggs ◽

S. Wagner ◽

S. Kotapati ◽

J. Schneider ◽

...

Keyword(s):

Overall Survival ◽

Median Overall Survival ◽

Cancer Therapies ◽

New Cancer Therapies

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A monocentric phase I study of vemurafenib plus cobimetinib plus PEG-interferon (VEMUPLINT) in advanced melanoma patients harboring the V600BRAF mutation

Journal of Translational Medicine ◽

10.1186/s12967-020-02680-7 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Ester Simeone ◽

Giosuè Scognamiglio ◽

Mariaelena Capone ◽

Diana Giannarelli ◽

Antonio M. Grimaldi ◽

...

Keyword(s):

Overall Survival ◽

Phase I ◽

Phase I Study ◽

Median Overall Survival ◽

Progression Free Survival ◽

Melanoma Cells ◽

Advanced Melanoma ◽

Free Survival ◽

Median Progression Free Survival ◽

Pre Treatment

Abstract Background Studies carried out in vitro and in a mouse model have shown that BRAF inhibitors enhance the effects of IFN-α on BRAFV600E melanoma cells through the inhibition of ERK. Therefore, the combination of vemurafenib and IFN-α in patients with BRAFV600E melanoma may provide therapeutic benefits; MEK inhibition may prevent the reactivation of the MAPK pathway induced by BRAF inhibitor resistance. Patients and methods In a phase I study, adult patients with advanced BRAFV600-mutated melanoma were treated with vemurafenib + PEG-IFN-α-2b or vemurafenib + cobimetinib + PEG-IFN-α-2b, to assess the safety of the combination and the upregulation of IFN-α/β receptor-1 (IFNAR1). Results Eight patients were treated; 59 adverse events with four serious ones (three related to study treatments) were reported. Patients with a pre-treatment IFNAR1 expression on ≤ 35% melanoma cells had a median progression-free survival of 12.0 months (range: 5.6–18.4 months) and a median overall survival of 31.0 months (range: 19.8–42.2 months), while patients with a pre-treatment IFNAR1 expression on > 35% of melanoma cells had a median progression-free survival of 4.0 months (range: 0–8.8; p = 0.03), and a median overall survival of 5 months (p = 0.02). Following treatment, responders had higher levels of growth-suppressor genes, including GAS1 and DUSP1, and genes involved in a metabolically robust immune response, including FAP. Conclusion Our study supports the overall safety of the vemurafenib + PEG-IFN-α-2b + cobimetinib combination. IFNAR1 expression levels correlated with response to treatment, including survival. Vemurafenib + PEG-IFN-α-2b + cobimetinib would have difficulty finding a niche in the current treatment scenario for advanced melanoma, but we speculate that our findings may contribute to identify subjects particularly responsive to treatment. Trial registration: The study was registered at clinicaltrials.gov (NCT01959633). Registered 10 October 2013, https://clinicaltrials.gov/ct2/show/NCT01959633

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Glioblastoma Treatment with Temozolomide and Bevacizumab and Overall Survival in a Rural Tertiary Healthcare Practice

BioMed Research International ◽

10.1155/2018/6204676 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 6

Author(s):

Tonia C. Carter ◽

Rafael Medina-Flores ◽

Benjamin E. Lawler

Keyword(s):

Overall Survival ◽

Median Overall Survival ◽

Standard Of Care ◽

Healthcare Setting ◽

Primary Brain Tumor ◽

Newly Diagnosed ◽

Treatment Regimens ◽

Healthcare Practice ◽

Tertiary Healthcare ◽

The Impact

Background. The efficacy of temozolomide (TMZ) chemotherapy for treating newly diagnosed glioblastoma (GBM), a primary brain tumor with short survival, was demonstrated in a clinical trial in 2005, and since then, the standard-of-care for newly diagnosed GBM has been maximal safe surgery followed by 60 Gray of radiation with concomitant and adjuvant TMZ (standard radiotherapy and TMZ). In 2009, clinical trials also reported on the efficacy of bevacizumab for treating recurrent GBM. We performed a retrospective cohort study to evaluate the impact of treatment regimens on overall survival for patients with GBM at a rural tertiary healthcare practice. Methods. We retrospectively reviewed the medical records of 307 consecutive, newly diagnosed GBM patients at one institution between 1995 and 2012 and assessed treatment patterns. We also compared overall survival according to the treatment received. Results. Only 0.6% (1/163) of patients diagnosed before 2005 received standard radiotherapy and TMZ versus 36.1% (52/144) of patients diagnosed since 2005 (P < 0.0001). For patients who received standard radiotherapy and TMZ, the median overall survival was 17.0 months versus 7.0 months for patients who received 60 Gray of radiation but no chemotherapy (P = 0.0000078). The median overall survival was 15.4 months in the 19 patients treated with bevacizumab monotherapy at first GBM recurrence versus 6.8 months in the 32 patients with no treatment at first GBM recurrence (P = 0.00015), but patients who received bevacizumab were younger and more likely to have had a surgical resection and 60 Gray of radiation at diagnosis. Conclusions. TMZ and bevacizumab therapies were rapidly adopted in a rural tertiary healthcare setting, and patients who received these treatments had increased overall survival. However, advantageous prognostic factors in patients who received bevacizumab at recurrence may have influenced the extent of the increase in overall survival attributed to this treatment.

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Requirements on Dimensions for a Maturity Model for Smart Grids Based on Two Case Studies

Advances in Systems Analysis, Software Engineering, and High Performance Computing - Balancing Agile and Disciplined Engineering and Management Approaches for IT Services and Software Products ◽

10.4018/978-1-7998-4165-4.ch014 ◽

2021 ◽

pp. 271-292

Author(s):

Agnetha Flore ◽

Jorge Marx Goméz

Keyword(s):

Requirements Engineering ◽

Smart Grids ◽

Future Research ◽

Maturity Model ◽

Literature Research ◽

Research Activities ◽

First Case ◽

Agile Approach ◽

Further Development

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Treatment of recurrent malignant glioma with G207, a genetically engineered herpes simplex virus-1, followed by irradiation: Phase I study results

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.2042 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 2042-2042

Author(s):

M. Karrasch ◽

G. Y. Gillespie ◽

E. Braz ◽

P. G. Liechty ◽

L. B. Nabors ◽

...

Keyword(s):

Overall Survival ◽

Radiation Therapy ◽

Herpes Simplex Virus ◽

Herpes Simplex ◽

Phase I ◽

Malignant Glioma ◽

Phase I Study ◽

Median Overall Survival ◽

Recurrent Malignant Glioma ◽

Simplex Virus

2042 Background: G207 is a doubly mutated (deletion of both γ134.5 loci, insertional inactivation of UL39) herpes simplex virus (HSV)-1. Safety and efficacy of intracerebral inoculations of G207 to patients suffering from recurrent malignant gliomas have been demonstrated in previous clinical trials. Methods: In this phase I clinical trial, a total of 1 x 109 plaque forming units (pfu) G207 were administered by five stereotactic injections of 0.2 mL each into regions of recurrent malignant glioma defined by MRI, followed by focal radiation therapy 24 hours post injection. Included patients suffered from inoperable pathologically proven recurrent glioblastoma multiforme (GBM) or anaplastic astrocytoma (AA) which was progressive despite radiotherapy or chemotherapy and failed external beam radiotherapy > 5 Gray prior to study enrolment. Results: 9 patients were treated in this phase I study. 5 patients were suffering from relapsed GBM, 4 patients were suffering from relapsed AA. 1 month after treatment, 3 patients (3xGBM) showed SD, 2 patients (1xGBM, 1xAA) PR, and 4 patients (1xGBM, 3xAA) PD. The 2 patients with initial PR (1xGBM, 1xAA) were re-treated with G207/Irradiation at time point of tumor recurrence, showing PR one month after re-treatment again. Median overall survival time for all 9 patients was 229 days (7.6 months), with one patient still alive at time of abstract submission. In patients suffering from relapsed GBM, mOS was 7.4 months, in patients suffering from relapsed AA, mOS was 9.25 months. 20 serious adverse events occurred in this study, only 3 were possible/probable related to G207/irradiation. Within persistent areas of tumor, HSV staining was present by using a polyclonal antibody for HSV, indicating intratumoral G207 replication (proof of concept). Conclusions: In 9 patients suffering from relapsed GBM or AA, stereotactic intracerebral G207 inoculation followed by radiation therapy was feasible, safe, and induced clinically relevant responses. G207/Irradiation re-treatment was possible and induced anew clinical responses. Median overall survival is superior to published data in this patient population. Therefore, further clinical development of G207 in GBM is medically reasonable. [Table: see text]

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Prognostic Value of Palliative Prognostic Index for Hospitalized Patients With End-of-Life Hematologic Malignancies in a Japanese University Hospital

JCO Oncology Practice ◽

10.1200/op.21.00243 ◽

2021 ◽

pp. OP.21.00243

Author(s):

Hiroko Iizuka-Honma ◽

Toru Mitsumori ◽

Seiichiro Yoshikawa ◽

Haruko Takizawa ◽

Masaaki Noguchi

Keyword(s):

Overall Survival ◽

End Of Life ◽

Solid Tumors ◽

Median Overall Survival ◽

Prediction Models ◽

Prognostic Index ◽

Hematologic Malignancies ◽

Hospitalized Patients ◽

University Hospital ◽

Palliative Prognostic Index

PURPOSE Uncertainty of prognosis is one reason patients with hematologic malignancies receive aggressive therapy near end of life more often than those with advanced solid tumors. It is unknown whether end-of-life prognosis prediction models are useful for patients with hematologic malignancies, especially hospitalized patients receiving chemotherapy, because most prognostic models were developed for patients with solid tumors. The purpose of this study was to evaluate the prognostic accuracy of the Palliative Prognostic Index (PPI) for end-of-life patients with advanced hematologic malignancies. METHODS We retrospectively reviewed the records of 143 patients who became resistant to standard chemotherapy and died of disease progression in our university hospital hematology ward between May 2015 and November 2019. Patients were classified according to PPI scores (groups: A, PPI ≤ 2.0; B, 2.0 < PPI ≤ 4.0; and C, PPI > 4.0) based on their clinical charts at admission. The median overall survival for each patient (95% confidence interval) was calculated using the Kaplan-Meier method. Log-rank tests were used to determine significant differences between survival curves. RESULTS Median patient age was 76 years (range: 39-92 years), and 59% were men. Median overall survival times in the PPI groups A, B, and C were 58 days, 36 days, and 10 days, respectively. Statistically significant differences in survival time were observed between the groups ( P < .01); prediction accuracy was similar to that for patients with different diagnoses. CONCLUSION The usefulness of PPI was validated for near-end-of-life hospitalized patients with hematologic malignancies.

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Management of Optic Neuritis in Ayurveda - A Special Case Report

Journal of Ayurveda and Integrated Medical Sciences (JAIMS) ◽

10.21760/jaims.v3i5.13847 ◽

2018 ◽

Vol 3 (5) ◽

Author(s):

Dr. Harsha S. ◽

Dr. Mamatha KV.

Keyword(s):

Optic Nerve ◽

Optic Neuritis ◽

Visual Information ◽

Vision Loss ◽

Specific Treatment ◽

Interesting Case ◽

Treatment Modalities ◽

Further Development ◽

Special Case

The optic nerve carries visual information from your eye to your brain. Optic neuritis is when your optic nerve becomes inflamed. Optic neuritis can flare up suddenly from an infection or nerve disease. The inflammation usually causes temporary vision loss that typically happens in only one eye. Those with Optic neuritis sometimes experience pain. As you recover and the inflammation goes away, your vision will likely return. There are no direct references in our classics regarding optic neuritis but can be contemplated as a condition by name Parimlayi Timira. The specific management as such is not cited but a transcendence approach can be done with adopting the treatment which has the ability to pacify the already occurred pathology and prevent the further development of the disease. One such interesting case study on Optic neuritis is elaborated here where in specific treatment modalities (Shodana, Shamana and Kriyakalpas) played role in pacifying the condition.

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