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Controversies in the Treatment of Elderly Patients With Newly Diagnosed Glioblastoma

Matthias Holdhoff and Marc C. Chamberlain

Approximately half of all patients with glioblastoma are older than 65 years and nearly one-quarter are older than 70 years, with a rising incidence of this disease in the elderly population. The life expectancy of elderly patients with glioblastoma is significantly shorter than in younger patients. Potential explanations for this abbreviated survival include differences in tumor biology, reduced use of therapies, enhanced toxicity of treatment, or diminished efficacy of available therapies with increasing age. The current standard treatment of newly diagnosed, protocol-eligible, nonelderly patients with glioblastoma is based on the randomized prospective EORTC/NCIC study that included patients aged 18 to 70 years with a performance status of ECOG 0 to 2. Limited single-institution retrospective series suggest that clinically fit elderly patients may benefit from a similar treatment regimen. However, no randomized trial has been performed in the elderly population using this regimen. Available prospective randomized clinical trials in the elderly population with glioblastoma have shown that radiotherapy is superior to supportive care only, that single-modality hypofractionated radiotherapy (reduced dose and shorter treatment schedule) is an alternative to single-modality standard fractionated radiotherapy, and that single-agent temozolomide is equivalent to radiotherapy alone. This article summarizes published data of current patterns of care in elderly patients and reviews published evidence as it pertains to the benefit of different treatment modalities in elderly patients with glioblastoma. Notwithstanding the previously mentioned randomized trials, the optimal treatment of elderly patients with glioblastoma remains controversial.

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Integrating POLST into Palliative Care Guidelines: A Paradigm Shift in Advance Care Planning in Oncology

Patricia A. Bomba and Daniel Vermilyea

Because predicting and outlining guidance for all possible scenarios is difficult, advance directives are rarely sufficiently precise to dictate patient preferences in specific situations as a disease progresses. Nonetheless, advance care planning is an essential process that should begin at the time of diagnosis, if not already initiated, to ensure that all patient and family rights are preserved. Communicating effectively with the patient and family and having the patient designate a surrogate decision-maker are critical. Attention must be paid to resolving conflicts among patient values and preferences and those of family and the health care team. Patient-centered goals for care and expectations should be elicited at first assessment and reassessed frequently as conditions change. As a disease progresses, advance directives are rarely precise enough to predict all possible scenarios and outline guidance for care. Therefore, for patients with advanced metastatic cancer and a potential life expectancy of less than 1 year, converting patient-centered treatment goals into actionable medical orders while the patient maintains capacity is a more effective way to ensure that patient preferences are honored. Physician Orders for Life-Sustaining Treatment (POLST) and similar medical order forms provide explicit direction about resuscitation status (“code status”) if the patient is pulseless and apneic. POLST also includes directions about additional interventions the patient may or may not want. A decade of research in Oregon has proved that the POLST Paradigm Program more accurately conveys end-of-life preferences that are more likely to be followed by medical professionals than traditional advance directives alone.

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Issues of Imatinib and Pregnancy Outcome

Jane Apperley

The introduction of tyrosine kinase inhibitors into clinical practice now offers most patients with chronic myelogenous leukemia lengthy remissions and the possibility of normal life expectancies. These improved survivals have resulted in the need to address issues relating to quality of life, including fertility and procreation. Treatment may require lifelong daily therapy with drugs that might inhibit proteins essential to gonadal function, implantation, and embryogenesis. Animal data suggest that imatinib at standard dosages is unlikely to impair fertility in either adult male or female animals. However, human data remain limited, particularly in children and adolescents. Children born to men who are actively taking imatinib at conception seem healthy, and current advice is not to discontinue treatment. In contrast, data are less encouraging for children born to women exposed to imatinib during pregnancy. Although numbers are small, a disturbing cluster of rare congenital malformations has prevented imatinib from being recommended safely, particularly during the period of organogenesis. Alternative strategies for managing pregnancy in chronic myelogenous leukemia include one or both of regular leukapheresis and interferon-α. Pregnancy in advanced-phase disease presents particular problems.

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Geriatric Assessment in Older Patients with Breast Cancer

Heidi Klepin, Supriya Mohile, and Arti Hurria

Most cases of breast cancer are diagnosed in older adults. Older women have an increased risk for breast cancer–specific mortality and are at higher risk for treatment-associated morbidity than younger women. However, they are also less likely to be offered preventive care or adjuvant therapy for this disease. Major gaps in evidence exist regarding the optimal evaluation and treatment of older women with breast cancer because of significant underrepresentation in clinical trials. Chronologic age alone is an inadequate predictor of treatment tolerance and benefit in this heterogeneous population. Multiple issues uniquely associated with aging impact cancer care, including functional impairment, comorbidity, social support, cognitive function, psychological state, and financial stress. Applying geriatric principles and assessment to this older adult population would inform decision making by providing estimates of life expectancy and identifying individuals most vulnerable to morbidity. Ongoing research is seeking to identify which assessment tools can best predict outcomes in this population, and thus guide experts in tailoring treatments to maximize benefits in older adults with breast cancer.

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Interventional Therapies for Cancer Pain Management: Important Adjuvants to Systemic Analgesics

Anthony Eidelman, Traci White, and Robert A. Swarm

Optimized use of systemic analgesics fails to adequately control pain in some patients with cancer. Commonly used analgesics, including opioids, nonopioids (acetaminophen and non-steroidal anti-inflammatory drugs), and adjuvant analgesics (anticonvulsants and antidepressants), have limited analgesic efficacy, and their use is often associated with adverse effects. Without adequate pain control, patients with cancer not only experience the anguish of poorly controlled pain but also have greatly diminished quality of life and may even have reduced life expectancy. Interventional pain therapies are a diverse set of procedural techniques for controlling pain that may be useful when systemic analgesics fail to provide adequate control of cancer pain or when the adverse effects of systemic analgesics cannot be managed reasonably. Commonly used interventional therapies for cancer pain include neurolytic neural blockade, spinal administration of analgesics, and vertebroplasty. Compared with systemic analgesics, which generally have broad indications for control of pain, individual interventional therapies generally have specific, narrow indications. When appropriately selected and implemented, interventional pain therapies are important components of broad, multimodal cancer pain management that significantly increases the proportion of patients able to experience adequate pain control.

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Making the Grade: The Impact of Low-Grade Toxicities on Patient Preference for Treatment With Novel Agents

Emily H. Castellanos, Sheau-chiann Chen, Hillary Drexler, and Leora Horn

Background: Targeted therapies have shown clinical benefit in the treatment of solid tumors. The toxicity profiles and treatment duration and schedule of these agents differ considerably from those of traditional chemotherapy. Many studies of targeted therapies report sizeable numbers of grade 1 or 2 toxicities. We sought to determine whether anticipation of low-grade toxicities and treatment logistics impact patient willingness to undergo therapy. Patients and Methods: A total of 209 patients with cancer (101 lung and 108 breast) were surveyed at the Vanderbilt-Ingram Cancer Center regarding willingness to comply with treatment based on anticipated efficacy, dosing convenience, and toxicity profiles. All toxicities were Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade 1 and 2. Willingness to comply with treatment depending on toxicity, anticipated benefit, cancer type, and dosing convenience was compared. Results: A substantial number of patients (2.9%–48.8%, depending on the toxicity described) professed unwillingness to undergo treatment because of anticipated grade 1 and 2 toxicities. Gastrointestinal and constitutional toxicities had a stronger negative impact on patient willingness to undergo therapy than dermatologic toxicity. Patients with lung cancer were significantly more likely to accept dermatologic and gastrointestinal toxicities than those with breast cancer. Willingness to tolerate toxicities correlated with expected benefit in terms of life expectancy and chance of cure. Lengthy travel distance for treatment negatively impacted willingness to undergo treatment. Conclusions: Anticipation of low-grade toxicities and dosing inconvenience negatively impacts patient willingness to be treated, which may affect adherence and therapeutic outcomes from therapy. Long-term tolerability should be considered when developing and assessing the impact of novel agents.

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Should Resource Constraints Guide Global Guidelines?

Benjamin O. Anderson

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HSR20-103: Years of Potential Life Lost Due to Cervical and Uterine Cancer Deaths in the United States, 2000-2016

Chizoba Nwankwo and Shelby Corman

cervical and uterine cancer in the United States between 2000 and 2016. Methods: YoPLL due to cervical and uterine cancer in each year was calculated by summing, for each death, the remaining life expectancy at the age of death. The number of deaths by

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Will Risk Evaluation and Mitigation Strategies Ever Be Accepted?

Edward C. Li

: 1) performance expectancy, 2) effort expectancy, 3) social influence, and 4) facilitating conditions to REMS. 5 Figure 2 Survey results: physician participation in Risk Evaluation and Mitigation Strategy (REMS) programs for specific drugs

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Primary Androgen Deprivation Therapy for Nonmetastatic Prostate Cancer in Asia: Unique or Not?

Masaki Shiota

guidelines, including the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer, recommend active surveillance, radical therapy, or observation for nonmetastatic prostate cancer based on disease status and patient life expectancy