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The NCCN Guidelines for Older Adult Oncology address specific issues related to the management of cancer in older adults, including screening and comprehensive geriatric assessment (CGA), assessing the risks and benefits of treatment, preventing or decreasing complications from therapy, and managing patients deemed to be at high risk for treatment-related toxicity. CGA is a multidisciplinary, in-depth evaluation that assesses the objective health of the older adult while evaluating multiple domains, which may affect cancer prognosis and treatment choices. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines providing specific practical framework for the use of CGA when evaluating older adults with cancer.

The NCCN Guidelines for Older Adult Oncology address specific issues related to the management of cancer in older adults, including screening and comprehensive geriatric assessment (CGA), assessing the risks and benefits of treatment, preventing or decreasing complications from therapy, and managing patients deemed to be at high risk for treatment-related toxicity. CGA is a multidisciplinary, in-depth evaluation that assesses the objective health of the older adult while evaluating multiple domains, which may affect cancer prognosis and treatment choices. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines providing specific practical framework for the use of CGA when evaluating older adults with cancer.

PURPOSE: ASCO guidelines recommend palliative care (PC) referral for patients with advanced or metastatic cancer. Despite this, implementation has considerable hurdles. First-year oncology fellows at our institution identified low rates of PC utilization in their longitudinal clinic as a metric needing improvement. METHODS: A fellow-led multidisciplinary team aimed to increase PC utilization for patients with advanced cancer followed in he first-year fellows’ clinic from a baseline of 11.5% (5 of 43 patients, July to December of 2018) to 30% over a 6-month period. Utilization was defined as evaluation in the outpatient PC clinic hosted in the cancer center. The team identified the following barriers to referral: orders difficult to find in the electronic medical record (EMR), multiple consulting mechanisms (EMR, by phone, or in person), EMR request not activating formal consult, no centralized scheduler to contact or confirm appointment, and poor awareness of team structure. Plan-Do-Study-Act (PDSA) cycles were implemented based on identified opportunities. Data were obtained from the EMR. RESULTS: The first PDSA cycle included focus groups with stakeholders, standardizing referral process via single order set, identifying a single scheduler with bidirectional communication, and disseminating process changes. PDSA cycles were implemented from January to June of 2019. Rates of PC use increased from 11.5% before the intervention to 48.4% (48 of 99 patients) after the intervention. CONCLUSION: A multidisciplinary approach and classic quality improvement methodology improved PC use in patients with advanced cancer. The pilot succeeded given the small number of fellows, buy-in from stakeholders, and institutional and leadership support. Straightforward EMR interventions and ancillary staff use are effective in addressing underreferrals.

Cancer pain is a common symptom and syndrome in patients with a history of cancer. Up to 75% of patients with cancer will experience pain severe enough to require treatment with opioids during their illness and recovery course. Unrelieved pain can directly affect a patient's health, treatment, and quality of life. Ensuring safe and effective pain management while avoiding over-prescribing, overuse, and potential for aberrant use of opioids is of increasing importance, given the increase of reported cases of opioid diversion, overdose, and death. This coupled with other patient-, provider-, and system-based factors serve as barriers to timely and appropriate management of cancer related pain. Comprehensive assessment of the patient and his/her pain experience is critical to optimal pain management. Gaining an understanding of the severity, impact, and the type of pain allows for a multifaceted and individualized approach to pain management. Nonpharmacologic therapies, including relaxation techniques, acupuncture, and exercise, in combination with pharmacologic therapies, including nonopioids, opioids, and adjuvant therapies, provide adequate pain relief in up to 85% of cancer patients with pain. For patients with refractory complex pain, the addition of other therapies, including radiation, regional analgesia, neuroablative procedures, chemotherapy, and palliative surgery, will often provide excellent palliation in nearly all patients with cancer pain.

BACKGROUND Fatigue is prevalent and distressing among cancer survivors, but its subjective nature makes it difficult to identify. Fatigability, defined as task-specific fatigue, and endurance performance may be useful supplemental measures of functional status in cancer survivors. METHODS Fatigability, endurance performance, and cancer history were assessed every 2 years in Baltimore Longitudinal Study of Aging participants between 2007 and 2015. Fatigability was defined according to the Borg rating of perceived exertion scale after a 5-minute, slow treadmill walk; and endurance performance was calculated according to the ability and time to complete a fast-paced, 400-meter walk. The association between cancer history, fatigability, and endurance performance was evaluated using longitudinal analyses adjusted for age, sex, body mass index, and comorbidities. RESULTS Of 1665 participants, 334 (20%) reported a history of cancer. A combination of older age (>65 years) and a history of cancer was associated with 3.8 and 8.6 greater odds of high perceived fatigability and poor endurance, respectively (P < .01). Older adults with and without a history of cancer walked 42 and 23 seconds slower than younger adults without a history of cancer, respectively (P < .01). The median times to the development of high fatigability and poor endurance were shorter among those who had a history of cancer compared with those who had no history of cancer (P < .01). CONCLUSIONS The current findings suggest that a history of cancer is associated with fatigability and poor endurance and that this effect is significantly greater in older adults. Evaluating the effects of cancer and age on fatigability may illuminate potential pathways and targets for future interventions. Cancer 2018;124:1279-87. © 2018 American Cancer Society.

End-of-life decision making in cancer can be a complicated process. Patients and families encounter multiple providers throughout their cancer care. When the efforts of these providers are not well coordinated in teams, opportunities for high-quality, longitudinal goals of care discussions can be missed. This article reviews the case of a 55-year-old man with lung cancer, illustrating the barriers and missed opportunities for end-of-life decision making in his care through the lens of team leadership, a key principle in the science of teams. The challenges demonstrated in this case reflect the importance of the four functions of team leadership: information search and structuring, information use in problem solving, managing personnel resources, and managing material resources. Engaging in shared leadership of these four functions can help care providers improve their interactions with patients and families concerning end-of-life care decision making. This shared leadership can also produce a cohesive care plan that benefits from the expertise of the range of available providers while reflecting patient needs and preferences. Clinicians and researchers should consider the roles of team leadership functions and shared leadership in improving patient care when developing and studying models of cancer care delivery.

Fatigue is prevalent and distressing among cancer survivors, but its subjective nature makes it difficult to identify. Fatigability, defined as task-specific fatigue, and endurance performance may be useful supplemental measures of functional status in cancer survivors.Fatigability, endurance performance, and cancer history were assessed every 2 years in Baltimore Longitudinal Study of Aging participants between 2007 and 2015. Fatigability was defined according to the Borg rating of perceived exertion scale after a 5-minute, slow treadmill walk; and endurance performance was calculated according to the ability and time to complete a fast-paced, 400-meter walk. The association between cancer history, fatigability, and endurance performance was evaluated using longitudinal analyses adjusted for age, sex, body mass index, and comorbidities.Of 1665 participants, 334 (20%) reported a history of cancer. A combination of older age (65 years) and a history of cancer was associated with 3.8 and 8.6 greater odds of high perceived fatigability and poor endurance, respectively (P.01). Older adults with and without a history of cancer walked 42 and 23 seconds slower than younger adults without a history of cancer, respectively (P.01). The median times to the development of high fatigability and poor endurance were shorter among those who had a history of cancer compared with those who had no history of cancer (P.01).The current findings suggest that a history of cancer is associated with fatigability and poor endurance and that this effect is significantly greater in older adults. Evaluating the effects of cancer and age on fatigability may illuminate potential pathways and targets for future interventions. Cancer 2018;124:1279-87. © 2018 American Cancer Society.

Population studies support an increased incidence of most cancers among older adults. Colorectal cancer has high prevalence in the aging population, with a median age of 69 years at diagnosis and 74 years at death. The vast majority of patients with colon cancer (CC) will require chemotherapy treatments during their disease course, challenging oncologists with the task of tailoring therapy for older patients with CC in the face of limited evidence-based data to guide them. Factors such as comorbidity, performance status, cognitive function, and social support may affect decision making and complicate tolerance of any recommended therapy. In recent years, attention to the specific needs of the aging population with cancer has given rise to the field of geriatric oncology in general, and has generated an increasing fund of knowledge on which to base chemotherapy delivery for this specific population of patients with CC. This article will review the available data specifically for chemotherapy management of older patients with CC in the postoperative and metastatic settings.

The number of older individuals with cancer is increasing exponentially, mandating that oncologists contemplate more comprehensive and multidisciplinary approaches to treatment of this cohort. Recruitment of assessment instruments validated in older patients can be invaluable for guiding treatment and decision-making by both patients and providers, and can arguably contribute to improving outcomes and health-related quality of life. The Comprehensive Geriatric Assessment is one such validated instrument that can be used by oncologists to assess patient readiness and appropriateness for prescribed cancer therapy. As a multidisciplinary diagnostic and treatment process, it comprises functional status, cognitive status, social support, and advance care preferences, and is an ideal instrument for evaluating complex older individuals. It is well established that many older individuals with cancer travel with multiple comorbid illnesses, including cognitive impairment, and when presented with a cancer diagnosis struggle to choose from multiple treatment options. In addition to the complete medical history, the ability of patients to decide on a course of therapy in concert with their oncologist is critically important. Alternatively, many oncologists are conflicted as to whether true informed consent for treatment can be obtained from many older patients. Having a roadmap to decision-making capacity is therefore an inescapable imperative in geriatric oncology, because careful attention must be directed at identifying older patients with cancer who might benefit from these assessments and the individualized treatment plans that emerge.

Cancer is the leading cause of death in older adults aged 60 to 79 years. Older patients with good performance status are able to tolerate commonly used treatment modalities as well as younger patients, particularly when adequate supportive care is provided. For older patients who are able to tolerate curative treatment, options include surgery, radiation therapy (RT), chemotherapy, and targeted therapies. RT can be highly effective and well tolerated in carefully selected patients, and advanced age alone should not preclude the use of RT in older patients with cancer. Judicious application of advanced RT techniques that facilitate normal tissue sparing and reduce RT doses to organs at risk are important for all patients, and may help to assuage concerns about the risks of RT in older adults. These NCCN Guidelines Insights focus on the recent updates to the 2016 NCCN Guidelines for Older Adult Oncology specific to the use of RT in the management of older adults with cancer.

51 Background: ASCO guidelines recommend palliative care (PC) referral for patients with advanced or metastatic cancer. Despite this, implementation has considerable hurdles. 1st year oncology fellows at our institution identified low rates of palliative care in their longitudinal clinic as an avenue for improvement. Methods: A Fellow-led multidisciplinary team aimed to increase palliative care utilization for patients with advanced cancer followed in first-year fellows’ clinic from baseline 11.5% (5/43 patients, Jul-Dec, '18) to 30% over a 4-mo period. Utilization was defined as evaluation in the outpatient palliative care clinic hosted in the cancer center. The team identified several barriers to referral: orders difficult to find in EMR, multiple consulting mechanisms (EMR, by phone, in person), EMR request not activating formal consult, no centralized scheduler to contact/confirm appointment, and poor awareness of team structure. PDSA cycles were implemented based on identified opportunities. Data were obtained from the EMR. Results: The PDSA cycle included focus groups with stakeholders, standardizing referral process via single order set, identifying a single scheduler with bidirectional communication, and dissemination of process changes. The PDSA was implemented Jan-Apr '19. Rates of palliative care use increased from 11.5% pre-intervention to 43% (27/62 patients) post-intervention. In addition, median time to evaluation in palliative care clinic after placing a consult improved from 23 days (range, 10-60 days) to 12 days (range, 6-19 days). Conclusions: A multidisciplinary approach and classic QI methodology improved palliative care use for patients with advanced cancer. The pilot succeeded given the small number of fellows, buy-in from stakeholders, and institutional support of efforts. Straightforward EMR interventions and ancillary staff use are effective in addressing under referrals.

563 Background: Mismatch repair proficient (MMRp) colorectal cancer (CRC) is refractory to single-agent programmed cell death protein 1 (PD1) inhibitors. Cancer vaccines may prime the tumor microenvironment for anti-PD1 therapy. Colon GVAX is an allogeneic, whole-cell, GM-CSF-secreting vaccine that induces T-cell immunity against tumor-associated antigens. GVAX has previously been studied in combination with low-dose cyclophosphamide (Cy) to inhibit regulatory T cells. Methods: We conducted an open label, single-arm, phase 2 study of GVAX/Cy in combination with the PD1 inhibitor pembrolizumab in patients with MMRp CRC who had received at least two prior lines of therapy in the metastatic setting. Patients received pembrolizumab plus Cy on day 1, GVAX on day 2, of a 21 day cycle through 4 cycles, and were then continued on a maintenance regimen of pembolizumab every 3 weeks with cy/GVAX given every 12 weeks. Results: Seventeen patients were enrolled. There were no objective responses, and the disease control rate was 18% by RECIST and 29% by irRC. The median progression free survival was 2.7 months and the median overall survival was 7.0 months. Biochemical responses (≥30% decline in CEA) were observed in 7/17 (41%) of patients. Two patients (12%) had grade 3/4 adverse events that were attributed to study therapy. To test the hypothesis that the induction of a humoral response against CEA protein had resulted in the observed biochemical responses, we measured patient titers of anti-CEA antibodies. Anti-CEA antibody titers increased 13 of 13 patients (100%) with available paired pre- and on-treatment research blood samples, but the change in anti-CEA antibody titers were similar among CEA responders and non-responders. Multiplex immunohistochemistry performed on pre- and post- biopsy specimens will be reported at the conference. Conclusions: GVAX/Cy plus pembrolizumab is well tolerated in advanced MMRp CRC and resulted in CEA responses but not radiographic responses. PFS and OS compare favorably to historical controls in this small cohort. CEA responses were not observed with PD1 monotherapy in MMRp CRC, suggesting GVAX can modulate the antitumor immune response. Clinical trial information: NCT02981524.

Whether a patient should receive systemic therapy before or after definitive surgical or radiation therapy is unclear because the survival benefit is only 5% to 10%, but, in certain cases, the physical and economic costs of therapy may far outweigh the benefit. The task at hand is to apply these data to the older NSCLC patient. For certain individuals with significant comorbid illnesses or limited life expectancy, disease-free survival and improved quality of life must be weighed against the possible treatment-related burden needed to realize the demonstrated survival benefit of (neo) adjuvant chemotherapy. For fit patients with resectable NSCLC and a life expectancy of greater than 2 years, such therapies should be considered even though elderly patients may suffer increased but tolerable toxicity from chemotherapy, radiation, and surgery. At present, neoadjuvant therapy might be prescribed for older patients who are deemed borderline for curative surgery, who would benefit from tumor downstaging, or who would be best served with definitive radiation if the neoadjuvant response was suboptimal. As these and other insights are clarified and supported by trial-based evidence, the physician may be better able to tailor therapies to improve treatment outcomes and limit toxicity among all patients and, in particular, older patients.

Despite advances in cancer detection and treatment, cancer continues to be a major public health burden in the United States, and patients with advanced or refractory cancers carry much of this burden. The primary goal of cancer treatment is cure. However, most patients with advanced, metastatic, or recurrent disease do not benefit from this intent. Recent research studies have documented the role of chemotherapy in providing symptom control, preventing complications, prolonging life, and improving quality of life (QOL) in patients with incurable cancers. Although chemotherapy under these conditions is palliative, patients receiving chemotherapy or participating in research trials are excluded from receiving much needed palliative services, such as Hospice, based on current definitions, limitations, and models of palliative care. Application of palliative services on a continuum from the time of diagnosis through the end of life (EOL) has been recognized as beneficial in the treatment of patients with terminal diseases and has been addressed through trials assessing mixed management models, providing palliative and therapeutic options.

Patients with a variety of different primary cancers can develop intracranial metastases. Patients who develop intracranial metastases are often grouped into the same study population, and therefore an understanding of outcomes for patients with different primary cancers remain unclear.Adults who underwent intracranial metastatic tumor surgery from 1997-2011 at a single institution were retrospectively reviewed. Primary pathologies were compared using Fisher's exact and Student's t-test, and Cox regression analysis was used to identify factors associated with survival.About 708 patients underwent surgery during the reviewed period, where 269 (38%) had non-small cell lung cancer (NSCLC), 106 (15%) breast cancer (BC), 72 (10%) gastrointestinal (GI) cancers, 88 (12%) renal cell cancer (RCC), and 88 (12%) melanoma. The most notable differences were that NSCLC patients were older, BC younger, BC had more primary tumor control, and NSCLC less extracranial spread. BC had longer survival, RCC had longer local progression free survival (PFS), and NSCLC had longer distal PFS. The factors independently associated with survival for NSCLC (female, recursive partitioning analysis (RPA) class, primary tumor control, solitary metastasis, tumor size, adenocarcinoma, radiation, discharge to home), BC (age, no skull base involvement, radiation), GI cancer (age, RPA class, Karnofsky performance scale (KPS), lack of preoperative motor deficit, non-esophageal tumors, non-hemorrhagic tumors, avoidance of new deficits), melanoma (preoperative seizures, solitary metastasis, smaller tumor size, discharge to home, chemotherapy), and RCC (KPS, chemotherapy) were distinctly different.These differences between patients with different primary cancers support the fact that patients with intracranial disease are not all the same and should be studied by their primary pathology.

Analyses of genomic alterations in cell-free DNA (cfDNA) shed from tumors into the blood stream is rapidly advancing as a method to detect and genotype cancer. Liquid biopsy analyses are a favorable alternative to invasive tissue approaches, particularly for cancers in organs where tissue is difficult to obtain. As these methods become a clinical standard, the method for blood collection and plasma isolation will be an important consideration to ensure optimal assay performance with limited degradation of circulating tumor DNA (ctDNA). We compared blood collection and plasma isolation using both K2EDTA and cell-free DNA Streck™ BCT tubes to determine the stability of cfDNA and ctDNA in blood at room temperature or at 4°C. Blood was collected from nine cancer patients with KRAS mutations using K2EDTA and Streck™ BCT tubes. Over the course of seven days, cell lysis occurred in K2EDTA tubes at room temperature, releasing germline DNA into the blood (1300% increase over seven days), which significantly increased the number of total genomic equivalents. Additionally, we found that the volume of plasma collected from both tube types during blood fractionation decreased over time when tubes were at room temperature (an average of 3.5 mL vs. 1.0 mL, respectively). To evaluate the effect of storage conditions on performance of each tube type, blood was also collected from six cancer patients with KRAS or EGFR mutations and either maintained at room temperature or stored at 4°C for up to three days. Taken together, K2EDTA tubes stored at 4°C prevented cell lysis and preserved the ctDNA in a manner equivalent to Streck™ BCT tubes. These data demonstrate that liquid biopsies can be collected using either tube type with similar performance and appropriate consideration of storage conditions. Citation Format: Sonya T. Parpart-Li, Bjarne Bartlett, Maria Popoli, Vilmos Adleff, Julie Brahmer, Nilo Azad, Sarah Bonerigo, Ilene Browner, Amy Ryan, Victor Velculescu, Mark Sausen, Luis A. Diaz. Optimized plasma collection procedures for liquid biopsy analyses in cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3957.

The majority of patients with colon cancer are over the age of 65. Their treatment poses multiple challenges to the oncologist, as these patients may have age-related comorbidities, polypharmacy, and physical or physiologic changes associated with older age. These challenges include limited data on the ability to predict tolerance to anti-cancer therapy and the appropriate use of treatment modalities in the setting of comorbidity and concurrent frailty. The low number of older patients enrolled on large clinical trials results in a paucity of evidence to guide the oncologist in the appropriate management of this population. In early stage disease, clinical dilemmas arise regarding the ability of older patients to undergo successful curative surgical procedures and the risk/benefit ratio of adjuvant chemotherapy. The management of metastatic disease raises questions regarding the clinical benefit of various anti-cancer therapies and the role of combination therapy with possible increased toxicity in the non-curative setting. Overall, the available evidence demonstrates that fit older patients are able to tolerate treatment and derive similar clinical benefits as younger patients. Limited data are available to guide treatment for less fit, more vulnerable older patients. This lack of data leads to variations in treatment patterns in older adults, making them less likely to receive standard therapies. This review will provide an overview of the available data regarding the management of older adults with colon cancer in the adjuvant and metastatic settings.

Cancer is the leading cause of death in women and men aged 60 to 79 years. The biologic characteristics of certain cancers are different in older patients compared with their younger counterparts, and older patients also have decreased tolerance to chemotherapy. Nevertheless, advanced age alone should not be the only criteria to preclude effective cancer treatment that could improve quality of life or lead to a survival benefit in older patients. Treatment should be individualized based the nature of the disease, the physiologic status of the patient, and patient preferences. Chronologic age is not reliable in estimating life expectancy, functional reserve, or the risk of treatment complications. Whether cancer treatment is appropriate may be best determined through careful assessment of the older patient. CGA can be used to assess life expectancy and risk of morbidity from cancer in elderly patients, in turn enabling physicians to develop a coordinated plan for cancer treatment and guide interventions tailored to the patient’s problems.

Cancer is the leading cause of death in older adults aged 60 to 79 years. The biology of certain cancers and responsiveness to therapy changes with the patient's age. Advanced age alone should not preclude the use of effective treatment that could improve quality of life or extend meaningful survival. The challenge of managing older patients with cancer is to assess whether the expected benefits of treatment are superior to the risk in a population with decreased life expectancy and decreased tolerance to stress. These guidelines provide an approach to decision-making in older cancer patients based on comprehensive geriatric assessment and also include disease specific issues related to age in the management of some cancer types in older adults.