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Arvold N.D.,Dana Farber Brigham and Womens Cancer Center | Reardon D.A.,Center for Neuro Oncology
Clinical Interventions in Aging | Year: 2014

Age remains the most powerful prognostic factor among glioblastoma (GBM) patients. Half of all patients with GBM are aged 65 years or older at the time of diagnosis, and the incidence rate of GBM in patients aged over 65 years is increasing rapidly. Median survival for elderly GBM patients is less than 6 months and reflects less favorable tumor biologic factors, receipt of less aggressive care, and comorbid disease. The standard of care for elderly GBM patients remains controversial. Based on limited data, extensive resection appears to be more beneficial than biopsy. For patients with favorable Karnofsky performance status (KPS), adjuvant radiotherapy (RT) has a demonstrated survival benefit with no observed decrement in quality of life. Concurrent and adjuvant temozolomide (TMZ) along with RT to 60 Gy have not been prospectively studied among patients aged over 70 years but should be considered for patients aged 65-70 years with excellent KPS. Based on the recent NOA-08 and Nordic randomized trials, testing for O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation should be performed routinely immediately after surgery to aid in adjuvant treatment decisions. Patients aged over 70 years with favorable KPS, or patients aged 60-70 years with borderline KPS, should be considered for monotherapy utilizing standard TMZ dosing for patients with MGMT-methylated tumors, and hypofractionated RT (34 Gy in ten fractions or 40 Gy in 15 fractions) for patients with MGMT-unmethylated tumors. The ongoing European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada trial will help clarify the role for concurrent TMZ with hypofractionated RT. For elderly patients with poor KPS, reasonable options include best supportive care, TMZ alone, hypofractionated RT alone, or whole brain RT for symptomatic patients needing to start treatment urgently. Given the balance between short survival and quality of life in this patient population, optimal management of elderly GBM patients must be made individually according to patient age, MGMT methylation status, performance score, and patient preferences. © 2014 Arvold and Reardon. Source

Wilder R.B.,Moffitt Cancer Center | Buyyounouski M.K.,Fox Chase Cancer Center | Efstathiou J.A.,Massachusetts General Hospital | Beard C.J.,Dana Farber Brigham and Womens Cancer Center
International Journal of Radiation Oncology Biology Physics | Year: 2012

Virtually all patients with Stage I testicular seminoma are cured regardless of postorchiectomy management. For patients treated with adjuvant radiotherapy, late toxicity is a major concern. However, toxicity may be limited by radiotherapy techniques that minimize radiation exposure of healthy normal tissues. This article is an evidence-based review that provides radiotherapy treatment planning recommendations for testicular seminoma. The minority of Stage I patients who choose adjuvant treatment over surveillance may be considered for (1) para-aortic irradiation to 20 Gy in 10 fractions, or (2) carboplatin chemotherapy consisting of area under the curve, AUC = 7 × 1-2 cycles. Two-dimensional radiotherapy based on bony anatomy is a simple and effective treatment for Stage IIA or IIB testicular seminoma. Centers with expertise in vascular and nodal anatomy may consider use of anteroposterior- posteroanterior fields based on three-dimensional conformal radiotherapy instead. For modified dog-leg fields delivering 20 Gy in 10 fractions, clinical studies support placement of the inferior border at the top of the acetabulum. Clinical and nodal mapping studies support placement of the superior border of all radiotherapy fields at the top of the T12 vertebral body. For Stage IIA and IIB patients, an anteroposterior-posteroanterior boost is then delivered to the adenopathy with a 2-cm margin to the block edge. The boost dose consists of 10 Gy in 5 fractions for Stage IIA and 16 Gy in 8 fractions for Stage IIB. Alternatively, bleomycin, etoposide, and cisplatin chemotherapy for 3 cycles or etoposide and cisplatin chemotherapy for 4 cycles may be delivered to Stage IIA or IIB patients (e.g., if they have a horseshoe kidney, inflammatory bowel disease, or a history of radiotherapy). © 2012 Elsevier Inc. Source

Yakoumakis N.,Dana Farber Brigham and Womens Cancer Center
Journal of applied clinical medical physics / American College of Medical Physics | Year: 2012

In this work we used 4D dose calculations, which include the effects of shape deformations, to investigate an alternative approach to creating the ITV. We hypothesized that instead of needing images from all the breathing phases in the 4D CT dataset to create the outer envelope used for treatment planning, it is possible to exclude images from the phases closest to the inhale phase. We used 4D CT images from 10 patients with lung cancer. For each patient, we drew a gross tumor volume on the exhale-phase image and propagated this to the images from other phases in the 4D CT dataset using commercial image registration software. We created four different ITVs using the N phases closest to the exhale phase (where N = 10, 8, 7, 6). For each ITV contour, we created a volume-modulated arc therapy plan on the exhale-phase CT and normalized it so that the prescribed dose covered at least 95% of the ITV. Each plan was applied to CT images from each CT phase (phases 1-10), and the calculated doses were then mapped to the exhale phase using deformable registration. The effect of the motion was quantified using the dose to 95% of the target on the exhale phase (D95) and tumor control probability. For the three-dimensional and 4D dose calculations of the plan where N = 10, differences in the D95 value varied from 3% to 14%, with an average difference of 7%. For 9 of the 10 patients, the reduction in D95 was less than 5% if eight phases were used to create the ITV. For three of the 10 patients, the reduction in the D95 was less than 5% if seven phases were used to create the ITV. We were unsuccessful in creating a general rule that could be used to create the ITV. Some reduction (8/10 phases) was possible for most, but not all, of the patients, and the ITV reduction was small. Source

Alexander B.M.,Dana Farber Brigham and Womens Cancer Center | Mehta M.P.,Northwestern University
Expert Review of Neurotherapeutics | Year: 2011

Recently, the isocitrate dehydrogenase (IDH) enzymes have become a focal point for research aimed at understanding the biology of glioma and identifying novel targets for therapy. Following the publication of a landmark genetic sequencing study in 2008, which identified IDH1 as a frequently mutated gene in glioblastoma, much work has been carried out to further characterize the frequency, associations and clinical implications of IDH1/2 mutations. Mutations in IDH genes are thought to occur early in tumorigenesis and define a subgroup of glioma that are characterized by specific metabolic changes and improved prognosis. At present, assays identifying tumors with IDH1 mutations are clinically useful as prognostic markers. While the mechanisms linking IDH1/2 mutations to tumor development are still under investigation, the cellular milieu created by these mutations offers potential targets for the development of novel therapeutics. © 2011 Expert Reviews Ltd. Source

Kulke M.H.,Dana Farber Brigham and Womens Cancer Center
Seminars in Oncology | Year: 2013

Neuroendocrine tumors (NETs) occur throughout the body, and share similar histologic characteristics. However, it has become increasingly evident that pancreatic NETs tend to respond differently to therapeutic agents than do other NET subtypes. In most cases, systemic therapy has been more effective in NETs of pancreatic origin than in NETs arising from other locations. Traditional systemic treatment options for pancreatic NETs include somatostatin analogs or cytotoxic chemotherapy. Recently, the biologically targeted agents everolimus and sunitinib were approved for use in patients with metastatic disease. Novel agents, as well as novel drug combinations, are currently under investigation. © 2013 Elsevier Inc. Source

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