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Article: A Novel Multimodal Approach to Refractory Brain Metastases: A Case Report.

Katlowitz, Kalman A / Beckham, Thomas H / Kudchadker, Rajat J / Wefel, Jeffrey / Elamin, Yasir Y / Weinberg, Jeffrey S

Advances in radiation oncology

2023 Volume 9, Issue 2, Page(s) 101349

Language	English
Publishing date	2023-08-15
Publishing country	United States
Document type	Case Reports
ISSN	2452-1094
ISSN	2452-1094
DOI	10.1016/j.adro.2023.101349
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Article ; Online: Assessment and Management of Cognitive Function in Patients with Prostate Cancer Treated with Second-Generation Androgen Receptor Pathway Inhibitors.

Wefel, Jeffrey S / Ryan, Charles J / Van, Julie / Jackson, James C / Morgans, Alicia K

CNS drugs

2022 Volume 36, Issue 5, Page(s) 419–449

Abstract: Preservation of cognitive function is an important outcome in oncology. Optimal patient management requires an understanding of cognitive effects of the disease and its treatment and an efficacious approach to assessment and management of cognitive ... ...

Abstract	Preservation of cognitive function is an important outcome in oncology. Optimal patient management requires an understanding of cognitive effects of the disease and its treatment and an efficacious approach to assessment and management of cognitive dysfunction, including selection of treatments to minimize the risk of cognitive impairment. Awareness is increasing of the potentially detrimental effects of cancer-related cognitive dysfunction on functional independence and quality of life. Prostate cancer occurs most often in older men, who are more likely to develop cognitive dysfunction than younger individuals; this population may be particularly vulnerable to treatment-related cognitive disorders. Prompt identification of treatment-induced cognitive dysfunction is a crucial aspect of effective cancer management. We review the potential etiologies of cognitive decline in patients with prostate cancer, including the potential role of androgen receptor pathway inhibitors; commonly used tools for assessing cognitive function validated in metastatic castration-resistant prostate cancer and adopted in non-metastatic castration-resistant prostate cancer trials; and strategies for management of cognitive symptoms. Many methods are currently used to assess cognitive function. The prevalence and severity of cognitive dysfunction vary according to the instruments and criteria applied. Consensus on the definition of cognitive dysfunction and on the most appropriate approaches to quantify its extent and progression in patients treated for prostate cancer is lacking. Evidence-based guidance on the appropriate tools and time to assess cognitive function in patients with prostate cancer is required.
MeSH term(s)	Aged ; Cognition ; Cognition Disorders ; Humans ; Male ; Prostatic Neoplasms, Castration-Resistant/pathology ; Quality of Life ; Receptors, Androgen
Chemical Substances	Receptors, Androgen
Language	English
Publishing date	2022-05-06
Publishing country	New Zealand
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1203800-3
ISSN	1179-1934 ; 1172-7047
ISSN (online)	1179-1934
ISSN	1172-7047
DOI	10.1007/s40263-022-00913-5
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Article ; Online: Perioperative considerations in patients with chemotherapy-induced cognitive impairment: a narrative review.

Guran, Ekin / Hu, Jian / Wefel, Jeffrey S / Chung, Caroline / Cata, Juan P

British journal of anaesthesia

2022 Volume 129, Issue 6, Page(s) 909–922

Abstract: Patients with cancer may suffer from a decline in their cognitive function after various cancer therapies, including surgery, radiation, and chemotherapy, and in some cases, this decline in cognitive function persists even years after completion of ... ...

Abstract	Patients with cancer may suffer from a decline in their cognitive function after various cancer therapies, including surgery, radiation, and chemotherapy, and in some cases, this decline in cognitive function persists even years after completion of treatment. Chemobrain or chemotherapy-induced cognitive impairment, a well-established clinical syndrome, has become an increasing concern as the number of successfully treated cancer patients has increased significantly. Chemotherapy-induced cognitive impairment can originate from direct neurotoxicity, neuroinflammation, and oxidative stress, resulting in alterations in grey matter volume, white matter integrity, and brain connectivity. Surgery has been associated with exacerbating the inflammatory response associated with chemotherapy and predisposes patients to develop postoperative cognitive dysfunction. As the proportion of patients living longer after these therapies increases, the magnitude of impact and growing concern of post-treatment cognitive dysfunction in these patients has also come to the fore. We review the clinical presentation, potential mechanisms, predisposing factors, diagnostic methods, neuropsychological testing, and imaging findings of chemotherapy-induced cognitive impairment and its intersection with postoperative cognitive dysfunction.
MeSH term(s)	Humans ; Chemotherapy-Related Cognitive Impairment ; Postoperative Cognitive Complications ; Cognitive Dysfunction/chemically induced ; Neuropsychological Tests ; Neoplasms/drug therapy ; Neoplasms/complications
Language	English
Publishing date	2022-10-19
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	80074-0
ISSN	1471-6771 ; 0007-0912
ISSN (online)	1471-6771
ISSN	0007-0912
DOI	10.1016/j.bja.2022.08.037
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Article ; Online: Functional impact of androgen-targeted therapy on patients with castration-resistant prostate cancer.

Beer, Tomasz M / Shore, Neal / Morgans, Alicia / Winters-Stone, Kerri / Wefel, Jeffrey S / George, Daniel J

BJUI compass

2022 Volume 3, Issue 6, Page(s) 424–433

Abstract: Context: Second-generation androgen receptor inhibitors (ARIs) extend metastasis-free survival, prolong overall survival, and delay symptoms when added to androgen deprivation therapy for the treatment of castration-sensitive or castration-resistant ... ...

Abstract	Context: Second-generation androgen receptor inhibitors (ARIs) extend metastasis-free survival, prolong overall survival, and delay symptoms when added to androgen deprivation therapy for the treatment of castration-sensitive or castration-resistant prostate cancer (CRPC). However, ARIs may adversely impact physical and cognitive function, thereby decreasing quality of life and prognosis. Objective: To evaluate the evidence regarding the potential effects of ARIs on physical and cognitive function and to contextualize how drug-related adverse effects may influence treatment decisions in CRPC. Evidence acquisition: We performed a literature search using MEDLINE from January 1998 to June 2020 using terms relating to prostate cancer, androgen deprivation, and physical and cognitive function. We selected 61 publications for analysis. Evidence synthesis: Treatment-induced deterioration in physical and cognitive function may impair the independence and well-being of patients with CRPC. Patient-reported outcomes from clinical trials of ARIs provide quantitative evidence of their impact on these domains, which appears to vary between ARIs, reflecting the different adverse event profiles of these agents. Thus, the risk of physical or cognitive dysfunction may be managed or mitigated by appropriate selection of treatment options. Studies in patients with CRPC have assessed the cognitive effects of ARIs with validated instruments, whereas quantitative analysis of the impact on physical function has been limited. Conclusion: Several validated instruments utilized for the assessment of physical and cognitive function in clinical studies have been adapted for clinical practice; however, consensus on the standardization of these assessments is required. Future clinical studies employing validated tools may generate data on the impact of ARIs and guide treatment decisions for patients with CRPC. Patient summary: We review the hormonal therapies used to treat men with prostate cancer and the effects they have on physical and cognitive function. We discuss how to measure these effects and how this may assist when choosing treatment.
Language	English
Publishing date	2022-08-24
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2688-4526
ISSN (online)	2688-4526
DOI	10.1002/bco2.179
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Article ; Online: NovaMin: likely clinical success.

Wefel, J S

Advances in dental research

2009 Volume 21, Issue 1, Page(s) 40–43

MeSH term(s)	Apatites/administration & dosage ; Apatites/therapeutic use ; Calcium Phosphates/administration & dosage ; Calcium Phosphates/therapeutic use ; Carbonates/administration & dosage ; Carbonates/therapeutic use ; Cariostatic Agents/administration & dosage ; Cariostatic Agents/therapeutic use ; Dental Caries/prevention & control ; Dentifrices/administration & dosage ; Dentifrices/therapeutic use ; Dentin Sensitivity/prevention & control ; Glass ; Humans ; Tooth Erosion/prevention & control ; Tooth Remineralization
Chemical Substances	Apatites ; Calcium Phosphates ; Carbonates ; Cariostatic Agents ; Dentifrices ; NovaMin ; hydroxycarbonate apatite
Language	English
Publishing date	2009
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	639406-1
ISSN	1544-0737 ; 0895-9374
ISSN (online)	1544-0737
ISSN	0895-9374
DOI	10.1177/0895937409335622
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Article ; Online: Interventions for the management of fatigue in adults with a primary brain tumour.

Day, Julia / Yust-Katz, Shlomit / Cachia, David / Wefel, Jeffrey / Tremont Lukats, Ivo W / Bulbeck, Helen / Rooney, Alasdair G

The Cochrane database of systematic reviews

2022 Volume 9, Page(s) CD011376

Abstract: Background: Fatigue is a common and disabling symptom in people with a primary brain tumour (PBT). The effectiveness of interventions for treating clinically significant levels of fatigue in this population is unclear. This is an updated version of the ... ...

Abstract	Background: Fatigue is a common and disabling symptom in people with a primary brain tumour (PBT). The effectiveness of interventions for treating clinically significant levels of fatigue in this population is unclear. This is an updated version of the original Cochrane Review published in Issue 4, 2016. Objectives: To assess the effectiveness and safety of pharmacological and non-pharmacological interventions for adults with PBT and clinically significant (or high levels) of fatigue. Search methods: For this updated review, we searched CENTRAL, MEDLINE and Embase, and checked the reference lists of included studies in April 2022. We also searched relevant conference proceedings, and ClinicalTrials.gov for ongoing trials. Selection criteria: We included randomised controlled trials (RCTs) that investigated any pharmacological or non-pharmacological intervention in adults with PBT and fatigue, where fatigue was the primary outcome measure. We restricted inclusion specifically to studies that enrolled only participants with clinically significant levels of fatigue to improve the clinical utility of the findings. Data collection and analysis: Two review authors (JD, DC) independently evaluated search results for the updated search. Two review authors (JD, SYK) extracted data from selected studies, and carried out a risk of bias assessment. We extracted data on fatigue, mood, cognition, quality of life and adverse events outcomes. Main results: The original review identified one study and this update identified a further two for inclusion. One study investigated the use of modafinil, one study the use of armodafinil and one study the use of dexamfetamine. We identified three ongoing studies. In the original review, the single eligible trial compared modafinil to placebo for 37 participants with a high- or low-grade PBT. One new study compared two doses of armodafinil (150 mg and 250 mg) to placebo for 297 people with a high-grade glioma. The second new study compared dexamfetamine sulfate to placebo for 46 participants with a low- or high-grade PBT. The evidence was uncertain for both modafinil and dexamfetamine regarding fatigue outcome measures, compared to controls, at study endpoint. Two trials did not reach the planned recruitment target and therefore may not, in practice, have been adequately powered to detect a difference. These trials were at a low risk of bias across most areas. There was an unclear risk of bias related to the use of mean imputation for one study because the investigators did not analyse the impact of imputation on the results and information regarding baseline characteristics and randomisation were not clear. The certainty of the evidence measured using GRADE was very low across all three studies. There was one identified study awaiting classification once data are available, which investigated the feasibility of 'health coaching' for people with a PBT experiencing fatigue. There were three ongoing studies that may be eligible for an update of this review, all investigating a non-pharmacological intervention for fatigue in people with PBT. Authors' conclusions: There is currently insufficient evidence to draw reliable and generalisable conclusions regarding potential effectiveness or harm of any pharmacological or non-pharmacological treatments for fatigue in people with PBT. More research is needed on how best to treat people with brain tumours with high fatigue.
MeSH term(s)	Adult ; Brain Neoplasms/complications ; Dextroamphetamine/therapeutic use ; Fatigue/etiology ; Fatigue/therapy ; Glioma ; Humans ; Modafinil/therapeutic use
Chemical Substances	Modafinil (R3UK8X3U3D) ; Dextroamphetamine (TZ47U051FI)
Language	English
Publishing date	2022-09-12
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Systematic Review
ISSN	1469-493X
ISSN (online)	1469-493X
DOI	10.1002/14651858.CD011376.pub3
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Article ; Online: Neurocognition and Health-Related Quality of Life Among Patients with Brain Tumors.

Noll, Kyle / King, Amanda L / Dirven, Linda / Armstrong, Terri S / Taphoorn, Martin J B / Wefel, Jeffrey S

Hematology/oncology clinics of North America

2021 Volume 36, Issue 1, Page(s) 269–282

Abstract: Patients with brain tumors experience great symptom burden across various domains of functioning, with associated decreases in health-related quality of life and general well-being. Impaired neurocognitive functioning is among the primary concerns of ... ...

Abstract	Patients with brain tumors experience great symptom burden across various domains of functioning, with associated decreases in health-related quality of life and general well-being. Impaired neurocognitive functioning is among the primary concerns of these patients. Unfortunately, most patients will experience such impairment at some point in the disease. However, impaired neurocognitive functioning, symptom burden, and well-being vary according numerous patient-, tumor-, and treatment-related factors. Recent work has furthered our understanding of these contributors to patient functioning and health-related quality of life and also points to various potential targets for prevention and intervention strategies, though more efficacious treatments remain needed.
MeSH term(s)	Brain Neoplasms ; Humans ; Quality of Life
Language	English
Publishing date	2021-10-25
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	93115-9
ISSN	1558-1977 ; 0889-8588
ISSN (online)	1558-1977
ISSN	0889-8588
DOI	10.1016/j.hoc.2021.08.011
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Article ; Online: Cognitive Changes in Cancer Survivors.

Hardy, Sara J / Krull, Kevin R / Wefel, Jeffrey S / Janelsins, Michelle

American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting

2018 Volume 38, Page(s) 795–806

Abstract: Advances in cancer treatments have led to substantially improved survival for patients with cancer. However, many patients experience changes in cognition as a side effect of both cancer and cancer treatment. This occurs with both central nervous system ( ...

Abstract	Advances in cancer treatments have led to substantially improved survival for patients with cancer. However, many patients experience changes in cognition as a side effect of both cancer and cancer treatment. This occurs with both central nervous system (CNS) tumors and non-CNS tumors and in both children and adults. Studies of patients with non-CNS cancer have shown that cancer-related cognitive impairment (CRCI), which can include changes in memory, executive function, attention, and processing speed, occurs in up to 30% of patients prior to any treatment and in up to 75% of patients during treatment. A subset of patients with non-CNS and CNS cancer appear to be at higher risk for CRCI, so much research has gone into identifying who is vulnerable. Risk factors for CRCI in adults include cognitive reserve, age, genetic factors, and ethnicity; risk factors for children include genetic factors, female sex, younger age at diagnosis, chemotherapy dose, and both dose and field size for radiation. Although the field has made substantial strides in understanding and treating CRCI, more research is still needed to improve outcomes for both pediatric and adult cancer survivors.
MeSH term(s)	Adult ; Age Factors ; Cancer Survivors/psychology ; Child ; Cognition ; Cognition Disorders/etiology ; Cognition Disorders/psychology ; Cognitive Dysfunction ; Combined Modality Therapy/adverse effects ; Combined Modality Therapy/methods ; Disease Susceptibility ; Humans ; Neoplasms/complications ; Neoplasms/pathology ; Neoplasms/therapy ; Risk Factors
Language	English
Publishing date	2018-09-19
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1548-8756 ; 1092-9118 ; 1548-8748
ISSN (online)	1548-8756
ISSN	1092-9118 ; 1548-8748
DOI	10.1200/EDBK_201179
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Article ; Online: Phase I dose-escalation study of procaspase-activating compound-1 in combination with temozolomide in patients with recurrent high-grade astrocytomas.

Holdhoff, Matthias / Nicholas, M Kelly / Peterson, Richard A / Maraka, Stefania / Liu, Li C / Fischer, James H / Wefel, Jeffrey S / Fan, Timothy M / Vannorsdall, Tracy / Russell, Meredith / Iacoboni, Michaella / Tarasow, Theodore M / Hergenrother, Paul J / Dudek, Arkadiusz Z / Danciu, Oana C

Neuro-oncology advances

2023 Volume 5, Issue 1, Page(s) vdad087

Abstract: Background: Procaspase-3 (PC-3) is overexpressed in various tumor types, including gliomas. Targeted PC-3 activation combined with chemotherapy is a novel strategy for treating patients with high-grade gliomas, with promising preclinical activity. This ... ...

Abstract	Background: Procaspase-3 (PC-3) is overexpressed in various tumor types, including gliomas. Targeted PC-3 activation combined with chemotherapy is a novel strategy for treating patients with high-grade gliomas, with promising preclinical activity. This study aimed to define safety and tolerability of procaspase-activating compound-1 (PAC-1) in combination with temozolomide (TMZ) for patients with recurrent high-grade astrocytomas. Methods: A modified-Fibonacci dose-escalation 3 + 3 design was used. PAC-1 was administered at increasing dose levels (DL; DL1 = 375 mg) on days 1-21, in combination with TMZ 150 mg/m Results: Eighteen patients were enrolled (13 GBM, IDH-wild type; 2 astrocytoma, IDH-mutant, grade 3; 3 astrocytoma, IDH-mutant, grade 4). Dose escalation was discontinued after DL3 (ie, PAC-1, 625 mg) due to lack of additional funding. Grade 3 toxicity was observed in 1 patient at DL1 (elevated liver transaminases) and 1 at DL 2 (headache). Two partial responses were observed at DL1 in patients with GBM, O Conclusions: Combination of PAC-1 and TMZ was well tolerated up to 625 mg orally daily and TMZ orally 150 mg/m
Language	English
Publishing date	2023-07-19
Publishing country	England
Document type	Journal Article
ZDB-ID	3009682-0
ISSN	2632-2498 ; 2632-2498
ISSN (online)	2632-2498
ISSN	2632-2498
DOI	10.1093/noajnl/vdad087
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Article: The Cognitive Effects of Radiotherapy for Brain Metastases.

Lehrer, Eric J / Jones, Brianna M / Dickstein, Daniel R / Green, Sheryl / Germano, Isabelle M / Palmer, Joshua D / Laack, Nadia / Brown, Paul D / Gondi, Vinai / Wefel, Jeffrey S / Sheehan, Jason P / Trifiletti, Daniel M

Frontiers in oncology

2022 Volume 12, Page(s) 893264

Abstract: Brain metastases are the most common intracranial neoplasm and are seen in upwards of 10-30% of patients with cancer. For decades, whole brain radiation therapy (WBRT) was the mainstay of treatment in these patients. While WBRT is associated with ... ...

Abstract	Brain metastases are the most common intracranial neoplasm and are seen in upwards of 10-30% of patients with cancer. For decades, whole brain radiation therapy (WBRT) was the mainstay of treatment in these patients. While WBRT is associated with excellent rates of intracranial tumor control, studies have demonstrated a lack of survival benefit, and WBRT is associated with higher rates of cognitive deterioration and detrimental effects on quality of life. In recent years, strategies to mitigate this risk, such as the incorporation of memantine and hippocampal avoidance have been employed with improved results. Furthermore, stereotactic radiosurgery (SRS) has emerged as an appealing treatment option over the last decade in the management of brain metastases and is associated with superior cognitive preservation and quality of life when compared to WBRT. This review article evaluates the pathogenesis and impact of cranial irradiation on cognition in patients with brain metastases, as well as current and future risk mitigation techniques.
Language	English
Publishing date	2022-06-30
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2022.893264
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