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Physicians’ Education Resource®, LLC, is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. These activites are not approved for AMA PRA Category 1 Credit

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Provider and Caregiver Connection™: Addressing Patient Concerns While Managing PER Pulse™ Recap

PER Pulse Recap

PER Pulse™ Recap


 

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PER Pulse™ Recap

Initial Treatment Options in Glioblastoma

Clinical outcomes for patients with glioblastoma remain ominous, with less than one-third of patients surviving beyond 1 year and less than 5% surviving 5 years out.1 The current standard for patients with newly diagnosed glioblastoma begins with maximal safe surgical resection if feasible, with previous studies showing the efficacy of resection for survival outcomes, particularly those with good performance status (PS).2,3 Gross total removal of these infiltrative tumors is especially challenging, given the need to preserve patient functioning as much as possible. After surgery, fractionated external beam radiation therapy is used as a standard therapy based upon early studies.4,5 Temozolomide is also commonly administered as part of treatment protocols for patients with glioblastoma. Tumor treating fields have also been incorporated into the treatment guidelines for patients with supratentorial disease as a class 2A recommendation in the adjuvant setting and a class 2B recommendation for recurrent disease.1

There are several tumor testing options that can help to guide initial treatment for patients with glioblastoma. Imaging with MRI may provide insight into tumor burden, as well as patterns of growth and potential deficits that the patient may be facing. Metabolic imaging modalities are also available, such as positron emission tomography scans and spectroscopy. Genetic factors may also be helpful in guiding therapy. The molecular O6-methylguanine-DNA-methyltransferase marker predicts a greater likelihood of deriving benefit from temozolomide therapy. This is the lone predictive marker that has been established thus far in the treatment of glioblastoma. The optimal duration of temozolomide has not yet been established. There does not appear to be additional benefit for extending temozolomide beyond 6 months.6 Timothy Cloughesy, MD and David Reardon, MD discuss initial treatment considerations and the incorporation of new treatment technology for patients with glioblastoma. For more details, please visit http://www.gotoper.com/.

References

  1. NCCN Clinical Practice Guidelines in Oncology. Central Nervous System Cancer. Version 1.2017. www.nccn.org/professionals/physician_gls/pdf/cns.pdf. Accessed September 18, 2017.
  2. Lacroix M, Abi-Said D, Fourney DR, et al. A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg. 2001;95(2):190-198.
  3. Li YM, Suki D, Hess K, Sawaya R. The influence of maximum safe resection of glioblastoma on survival in 1229 patients: can we do better than gross-total resection? J Neurosurg. 2016;124(4):977-988. doi: 10.3171/2015.5.JNS142087.
  4. Walker MD, Alexander E Jr, Hunt WE, et al. Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial. J Neurosurg. 1978;49(3):333-343.
  5. Kristiansen K, Hagen S, Kollevold T, et al. Combined modality therapy of operated astrocytomas grade III and IV. Confirmation of the value of postoperative irradiation and lack of potentiation of bleomycin on survival time: a prospective multicenter trial of the Scandinavian Glioblastoma Study Group. Cancer. 1981;47(4):649-652.
  6. Blumenthal DT, Gorlia T, Gilbert MR, et al. Is more better? The impact of extended adjuvant temozolomide in newly diagnosed glioblastoma: a secondary analysis of EORTC and NRG Oncology/RTOG. Neuro Oncol. 2017;19(8):1119-1126. doi:10.1093/neuonc/nox025.

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PER Pulse™ Recap

Precision oncology is helping to hone treatment approaches for patients with glioblastoma. Targeted therapies have been investigated to help improve survival outcomes for patients with glioblastoma, which was one of the initial tumor types analyzed by the Cancer Genome Atlas Network.1 This has helped to define some of the key abnormalities and pathways that may serve as treatment targets: the receptor tyrosine kinase/MAP kinase/PI3kinase pathway, the retinoblastoma pathway, and P53.2 Isocitrate dehydrogenase mutations are also being targeted,2 and other growth factors have emerged as potential targets for patients with glioblastoma.

Anti-VEGF agents, such as bevacizumab, have also been evaluated in the treatment of patients with glioblastoma, both in the recurrent and first-line settings.3,4 Glioblastoma tumors are highly vascularized, producing several proangiogenic factors, including VEGF. VEGF inhibitors inhibit tumor growth and brain edema associated with vasogenic activity.5 An OS benefit with this line of therapy has yet to be identified.4 It is also used in combination with immunotherapy, as a means of controlling the edema that may be associated with immunotherapy.

Immunotherapy options for patients with glioblastoma are an active area of clinical investigation, with several studies looking at checkpoint inhibitor therapy. Other studies are looking at ways to incorporate vaccine therapy for patients with glioblastoma.6 Chimeric antigen therapy treatments are being pursued as well. Immunotherapy options have generally been well tolerated in clinical studies, although durable responses remain elusive.6 Several obstacles complicate the implementation of immunotherapy, including immunogenic side effects and identification of drugs that can penetrate the blood-brain barrier, appropriate immunogenic antigens to target, and biomarkers.6 Timothy Cloughesy, MD and David Reardon, MD discuss the potential of investigational therapies for patients with glioblastoma; for more details, please visit http://www.gotoper.com/.

References

  1. Brennan CW, Verhaak RG, McKenna A, et al; TCGA Research Network. The somatic genomic landscape of glioblastoma [erratum in Cell. 2014;157(3):753]. Cell. 2013;155(2):462-477. doi: 10.1016/j.cell.2013.09.034.
  2. Touat M, Idbaih A, Sanson M, Ligon KL. Glioblastoma targeted therapy: updated approaches from recent biological insights. Ann Oncol. 2017;28(7):1457-1472. doi: 10.1093/annonc/mdx106.
  3. Tipping M, Eickhoff J, Ian Robins H. Clinical outcomes in recurrent glioblastoma with bevacizumab therapy: an analysis of the literature. J Clin Neurosci. 2017;44:101-106. doi: 10.1016/j.jocn.2017.06.070.
  4. Lombardi G, Pambuku A, Bellu L, et al. Effectiveness of antiangiogenic drugs in glioblastoma patients: a systematic review and analysis of randomized clinical trials. Crit Rev Oncol Hematol. 2017;111:94-102. doi: 10.1016/j.critrevonc.2017.01.018.
  5. Gil-Gil MJ, Mesia C, Rey M, Bruna J. Bevacizumab for the treatment of glioblastoma. Clin Med Insights Oncol. 2013;7:123-135. doi: 10.4137/CMO.S8503.
  6. Huang B, Zhang H, Lijuan G, et al. Advances in immunotherapy for glioblastoma multiforme. J Immunol Res. 2017;2017:3597613. doi: 10.1155/2017/3597613.

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PER Pulse™ Recap

Clinicians involved in the care of patients with glioblastoma must master several factors regarding patient communication. The successful management of these patients requires a multidisciplinary effort coordinated to accurately relay prognostic information for both patients and caregivers. Most patients do not have full prognostic awareness of the incurable nature of malignant gliomas. Therefore, patients with malignant gliomas who have memory impairment desire more prognostic information more frequently than those who do not have memory impairment, according to the results of a recent exploratory study.1

In addition to discussions regarding prognosis, it is important for clinicians to be able to have detailed discussions with their patients regarding potential adverse events (AEs) associated with different treatment modalities used for glioblastoma. Radiation is a cornerstone of therapy for initial management, and the cumulative effects can result in a variety of clinical manifestations, including patient somnolence, which may persist after the course of radiotherapy (RT). Temozolomide is an oral agent used in the treatment of glioblastoma that may produce such AEs as nausea, hair loss, fatigue, vomiting, headaches, and constipation. Lymphocytopenia can also occur with the use of temozolomide, and as opportunistic infections are a possibility, antibiotic prophylaxis against Pneumocystis carinii pneumonia should be administered when temozolomide is given with RT.2 The faculty discuss strategies to optimize communication with patients who have glioblastoma, as well as management of treatment-related AEs. This activity features an extensive patient and caregiver interview, conducted by Dr. Reardon, which explores many features of glioblastoma management and emphasizes the perspective of the patient when facing challenges.

References

  1. Diamond EL, Priferson HG, Correa DC, et al. Prognostic awareness, prognostic communication, and cognitive function in patients with malignant glioma [published online June 22, 2017]. Neuro Oncol. doi: 10.1093/neuonc/nox117.
  2. NCCN Clinical Practice Guidelines in Oncology. Central Nervous System Cancer. Version 1.2017. www.nccn.org/professionals/physician_gls/pdf/cns.pdf. Accessed September 18, 2017.




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