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113 Background: The Oncology Care Model (OCM) is a Medicare-sponsored delivery and payment innovation pilot under the broader concept of value-based care (VBC). OCM aims to provide better quality and coordinated cancer care at reduced cost. The OCM participants, 176 practices and 10 payers who provide care to nearly half of Medicare beneficiaries, entered into payment arrangements based on financial and performance accountability for episodes of care surrounding chemotherapy administration. We sought to understand the impact of OCM adoption on community physicians 3 years into the pilot. Methods: A live meeting in April 2019 convened a sample of US-based community oncologists to discuss “The OCM Experience”. Audience response survey methodology addressed: participation in OCM and/or related commercial programs, implementation, operation and perceptions of outcomes to patient care and practice. Results: Regarding VBC initiatives at the practices (n = 48) of 57 providers: 61% identified their practice participated in OCM, 31% in other commercial payer pathway program, and 17% in other commercial payer VBC reimbursement (not mutually exclusive). Regarding impact of OCM on improving access to care: 60% indicated having same-day appointments, 45% 24/7 HCP access, 22% weekend hours and 18% evening clinic hours. Regarding changes to patient care: 58% stated OCM driven initiatives reduced ER visits, 48% reduced hospitalizations, 62% increased palliative care referrals, and 54% increased hospice referrals. Regarding impact on practice: 41% felt an increased administrative burden with 50% hiring administrative staff, advanced practice providers, and patient navigators, but only 11% hiring physicians. The 13-component oncology care plan was reported by 53% as “not easy” to devise. The “most challenging” components included estimating total out of pocket expenses (61%) and creating a plan to address psychosocial needs (16%). 49% respondents found their practices’ OCM transformation meaningful and 46% found it not very/not at all meaningful. Conclusions: The impact of OCM/VBC transformation upon community oncologists and their practices appear to be quite profound, while the precise impact on their patients remains to be determined.

Limited-stage small-cell lung cancer (LSCLC) stands out as a disease entity for which the role of radiotherapy has been extensively studied and defined through prospective phase III trials in North America, Europe, and Asia. Meta-analyses in the 1990s confirmed a survival benefit with the addition of thoracic radiotherapy to chemotherapy, and the landmark Intergroup 0096 phase III trial demonstrated that altering the way thoracic radiotherapy was administered (twice daily) could affect overall survival. Additional randomized studies have assessed thoracic radiotherapy timing and sequencing, as reflected in current National Comprehensive Cancer Network guidelines that recommend concurrent thoracic radiotherapy starting with either the first or second cycle of chemotherapy. Likewise, substantial evidence supports a role for prophylactic cranial radiotherapy (PCI) in patients with responsive chest disease. Despite the multitude of clinical trials performed, relatively little prospective data are available to guide therapy for elderly patients, because they have been under-represented in these studies. Given the dearth of robust data for the elderly, and given a median age of patients with SCLC that approaches 70 years, the review by Corso et al, the article that accompanies this editorial, provides a meaningful look into the management of the disease in elderly patients. Their National Cancer Data Base analysis included more than 8,000 patients age 70 years or older who were treated in the modern era; although the results are disheartening, they are not completely unexpected. Perhaps most telling is that greater than 40% of patients did not receive thoracic radiotherapy and were treated with chemotherapy alone, presumably in an effort to avoid potential toxicities. As such, thoracic radiotherapy was less likely to be given with increasing age, higher stage, and the presence of medical comorbidities. Women were less likely to receive thoracic radiotherapy, for unclear reasons. Of note, treatment with chemoradiotherapy had the strongest association with survival on multivariable analysis. The benefit of chemoradiotherapy remained significant even when the analysis was revised to try to account for selection bias, including propensity score matching and a subset analysis that restricted the chemotherapy cohort to patients for whom radiation was explicitly recommended but not delivered. Likewise, the survival advantage with chemoradiotherapy retained significance in populations that traditionally were less likely to benefit from intensive therapy, such as in patients older than age 80 years and in patients with multiple medical comorbidities. The traditional belief that age alone is a determinant of benefit from aggressive therapy is not necessarily borne out from experience with prospective trials. For example, Radiation Therapy Oncology Group (RTOG) study 9410 was key in defining the superiority of concurrent chemoradiotherapy over sequential therapy for locally advanced non–small-cell lung cancer, yet a subset analysis showed that fit elderly patients derived the greatest benefit from concurrent therapy (median overall survival, 22.4 months with concurrent v 10.5 months with sequential therapy). Evidence is also available from prospective LSCLC trials, including Intergroup 0096, in which similar response rates and event-free survival rates were observed in patients younger and older than 70 years of age. Although 5-year overall survival favored younger patients, 16% of patients age 70 or older were still alive 5 years after therapy. Reviews of trials conducted by the National Cancer Institute of Canada, North Central Cancer Treatment Group, and Cancer and Leukemia Group B suggest that elderly patients tolerate treatment reasonably well and are not necessarily more likely to need treatment interruptions during thoracic radiotherapy, although severe treatment-related myelosuppression and fatalities may be more commonly observed in the older population. These data support chemoradiotherapy for the select group of elderly fit enough to qualify for prospective trials (generally Eastern Cooperative Oncology Group performance status [PS] of 0 to 2 and minimal weight loss before diagnosis), though closer monitoring for treatment-related effects appears indicated. Although the results from Corso et al are provocative, a major limitation is that the National Cancer Data Base lacks information on PS, on PCI, and on details of chemotherapy itself, all of which may affect outcomes. Because it is not clear why patients did not receive thoracic radiotherapy, the finding that patients treated with chemoradiotherapy do better than patients treated with chemotherapy alone may be substantially biased by including patients who are unable to tolerate initial chemotherapy or who have early disease progression and, therefore, never become candidates for thoracic radiotherapy. Despite these limitations, such retrospective analyses do provide important information regarding treatment in the real-world setting. The decision-making process in the elderly patient with LSCLC should address two questions: First, should the patient not be offered chemoradiotherapy for any reason? Second, does the patient understand the goals of treatment? It is noteworthy that a significant proportion of patients, particularly among the elderly, do not understand the goals of cancer treatment therapy. In the prevailing paradigm, the treating team may use clinical judgment to formulate a treatment plan. However, this may lead to prohibitive toxicity in those unable to JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 33 NUMBER 36 DECEMBER 2

Background Radiation-induced salivary gland tumors are well described in the literature, with mucoepidermoid cancer being the most common histologic entity. Epithelial-myoepithelial carcinoma is a rare tumor accounting for

Background This study was a retrospective analysis of elderly patients treated with stereotactic body radiotherapy (SBRT) in the setting of a multi-institutional consortium. Patients and Methods Three institutions pooled data on patients aged ≥ 75 years who received SBRT for stage I non–small-cell lung cancer (NSCLC). Forty-seven tumors in 46 patients were analyzed in patients aged 75 to 92 years (median, 82 years). Treatment was delivered during 2007 to 2009, with a median follow-up of 12.4 months. All patients underwent staging positron emission tomography–computed tomography (PET-CT), and 87% of tumors were confirmed by biopsy results. Total doses were 35 to 60 Gy, mainly in 3 to 5 fractions. All tumors were treated using a linear accelerator, with 96% of patients receiving 3-dimensional (3D) conformal RT and 4% undergoing intensity modulated RT (IMRT). Results At the time of analysis, the local failure rate was 2% (1 of 47). The regional failure rate was 9% (4 of 47). The distant failure rate was 6% (3 of 47). The combined failure rate was 15% (7 of 47) because 1 patient experienced both regional and distant failure. Among 20 tumors with any acute toxicity, there were no ≥ grade 3 toxicities. Pneumonitis (n = 10) grades 1 (n = 3) and 2 (n = 2) was seen in 15% and 10% of patients, respectively; these data were missing for 25% of patients. Conclusion SBRT in patients aged ≥ 75 years with stage I NSCLC proved tolerable, with toxicity rates comparable to those in younger patients. Excellent rates of local, regional, and distant control were achieved at a median follow-up of 12.4 months. This patient population represents a rapidly growing segment of the early lung cancer population, and SBRT appears to be a safe and effective treatment option for patients who are not optimal candidates for surgery.

Platinum-based adjuvant chemotherapy is the standard of care for patients with early-stage non–small cell lung cancer (NSCLC) treated with surgery. There is a paucity of data regarding the appropriate use of adjuvant chemotherapy in the treatment of older adults. In the absence of prospective randomized controlled trials specific to this population, the available evidence is limited to post hoc analyses of prospective studies in age-unselected populations and retrospective reviews of population databases. The available evidence for treatment of older adults with adjuvant therapy using cisplatin- and carboplatin-based therapy is reviewed. Strategies for future research, as well as the role of geriatric assessment in risk stratification, will be addressed.

Learning Objectives Compare characteristics of older patients that receive bevacizumab plus chemotherapy to those treated with chemotherapy alone for advanced NSCLC and CRC. Compare outcomes between older patients treated with bevacizumab plus chemotherapy to chemotherapy alone for advanced NSCLC and CRC. Describe toxicities in older patients treated with bevacizumab plus chemotherapy for advanced NSCLC and CRC. Background. Bevacizumab leads to improved survival for patients with metastatic colorectal cancer (CRC) or non-small cell lung cancer (NSCLC) when added to chemotherapy. Little is known about factors associated with receipt of bevacizumab, or whether bevacizamab is associated with increased toxicity when added to chemotherapy. Patients and Methods. We conducted a prospective study of patients aged ≥65 years, which evaluated the association between geriatric assessment (GA) metrics and chemotherapy toxicity. We examined differences in characteristics and outcomes of patients with CRC and NSCLC cancers who received bevacizumab with chemotherapy versus chemotherapy alone. Results. From a total of 207 patients, 27 (13%) received bevacizumab plus chemotherapy and 180 (87%) received chemotherapy alone. Groups were similar in sociodemographic and cancer characteristics. There were no baseline differences in GA domains except that patients with heart disease were less likely to receive bevacizumab (4% vs. 26%, p = .01). Seventy-eight percent of patients who had bevacizumab had grade 3–5 toxicity compared to only 57% who received chemotherapy alone (p = .06). Patients receiving bevacizumab were more likely to develop grade 3 hypertension than those who received chemotherapy alone (15% vs. 2%, p < .01). In multivariable analysis, factors associated with grade 3 or more toxicity included: bevacizumab (OR: 2.86, p = .04), CRC (OR: 2.54, p < .01), and baseline anemia (OR: 2.58, p = .03). Conclusion. Heart disease was more common in those who did not receive bevacizumab. Older patients who receive bevacizumab with chemotherapy have a higher odds of developing a grade 3–5 toxicity compared with those who receive chemotherapy alone.

Objective The purpose of this study was to correlate the significance of bone marrow hemophagocytosis and analyze outcome data in patients with suspected hemophagocytic lymphohistiocytosis (HLH) at a tertiary care hospital during the course of 5 years. Methods The pathology database of State University of New York Upstate Medical University, Syracuse, was searched for the terms "hemophagocytosis," "hemophagocytic syndrome," and "hemophagocytic lymphohistiocytosis" encompassing the period January 2009-December 2014. Bone marrow aspirate and biopsy specimens, along with ancillary laboratory studies, clinical course, and outcome data, were reviewed for each case. Results Of the 23 patients included in our study, HLH was diagnosed in 14 (60.8%). Bone marrow hemophagocytosis (HPC) was seen in a higher proportion of patients (78.5%) who were diagnosed as having HLH; however, 55.5% of the patients who were not diagnosed as having HLH also showed evidence of bone marrow HPC. Patients with malignancy-associated HLH had a markedly worse outcome compared with patients with nonmalignancy-associated HLH. Conclusions Although bone marrow HPC is fairly sensitive, it is not specific to establish a diagnosis of HLH. A high index of clinical suspicion together with early diagnosis and treatment is imperative to improve outcomes in patients suspected of having HLH.

Lung cancer is the leading cause of cancer-associated mortality in the USA. The median age at diagnosis of lung cancer is 70 years, and thus, about one-half of patients with lung cancer fall into the elderly subgroup. There is dearth of high level of evidence regarding the management of lung cancer in the elderly in the three broad stages of the disease including early-stage, locally advanced, and metastatic disease. A major reason for the lack of evidence is the underrepresentation of elderly in prospective randomized clinical trials. Due to the typical decline in physical and physiologic function associated with aging, most elderly do not meet the stringent eligibility criteria set forth in age-unselected clinical trials. In addition to performance status, ideally, comorbidity, cognitive, and psychological function, polypharmacy, social support, and patient preferences should be taken into account before applying prevailing treatment paradigms often derived in younger, healthier patients to the care of the elderly patient with lung cancer. The purpose of this chapter was to review the existing evidence of management of early-stage, locally advanced disease, and metastatic lung cancer in the elderly.

Frailty has been suggested as a construct for oncologists to consider in treating older cancer patients. Therefore, the authors assessed the potential of creating a deficit-accumulation frailty index (DAFI) from a largely self-administered comprehensive geriatric assessment (CGA).Five hundred patients aged ≥65 years underwent a CGA before receiving chemotherapy. A DAFI was constructed, resulting in a 51-item scale, and cutoff values were examined for patients in the robust/nonfrail (cutoff value, 0.0 0.2), prefrail (cutoff value, 0.2 0.35), and frail (cutoff value, ≥ 0.35) groups.Two hundred and fifty patients (50%) were nonfrail, 197 (39%) were prefrail, and 52 (11%) were frail. Older patients (aged ≥ 80 years) and those who had lower education, were living alone, and had higher stage disease were associated with prefrail/frail status. Prefrail/frail patients were more likely to have grade ≥3 toxicity but not to have a dose delay or reduction, and they were more likely to discontinue drug and be hospitalized. The association with grade ≥3 toxicity was attenuated by controlling for a toxicity risk calculator, but the other outcomes were not.A deficit-accumulation frailty index can be constructed from a CGA in older patients with cancer and can indicate the frailty status of the population. The frailty status so determined is associated both with outcomes likely because of chemotherapy toxicity and with those likely because of age-related physiologic and functional deficits and thus can be useful in the overall assessment of the patient. Cancer 2016;122:3865-3872. © 2016 American Cancer Society.

Purpose Older adults are at increased risk for chemotherapy toxicity, and standard oncology assessment measures cannot identify those at risk. A predictive model for chemotherapy toxicity was developed (N = 500) that consisted of geriatric assessment questions and other clinical variables. This study aims to externally validate this model in an independent cohort (N = 250). Patients and Methods Patients age ≥ 65 years with a solid tumor, fluent in English, and who were scheduled to receive a new chemotherapy regimen were recruited from eight institutions. Risk of chemotherapy toxicity was calculated (low, medium, or high risk) on the basis of the prediction model before the start of chemotherapy. Chemotherapy-related toxicity was captured (grade 3 [hospitalization indicated], grade 4 [life threatening], and grade 5 [treatment-related death]). Validation of the prediction model was performed by calculating the area under the receiver-operating characteristic curve. Results The study sample (N = 250) had a mean age of 73 years (range, 65 to 94 [standard deviation, 5.8]). More than one half of patients (58%) experienced grade ≥ 3 toxicity. Risk of toxicity increased with increasing risk score (36.7% low, 62.4% medium, 70.2% high risk; P < .001). The area under the curve of the receiver-operating characteristic curve was 0.65 (95% CI, 0.58 to 0.71), which was not statistically different from the development cohort (0.72; 95% CI, 0.68 to 0.77; P = .09). There was no association between Karnofsky Performance Status and chemotherapy toxicity (P = .25). Conclusion This study externally validated a chemotherapy toxicity predictive model for older adults with cancer. This predictive model should be considered when discussing the risks and benefits of chemotherapy with older adults.

Lung cancer is a disease of older adults. In the US and worldwide, more than 60% of patients being diagnosed are over the age of 65 years. The preferred treatment of stage I-II non-small-cell lung cancer (NSCLC) is surgical resection. Adjuvant chemotherapy with a platinum-based combination is the standard of care for patients with early-stage NSCLC after surgery. However, there have been no large prospective studies to test the efficacy of adjuvant chemotherapy in the elderly, the population most affected by lung cancer. The available evidence is limited to retrospective reviews of large population databases or post hoc analyses of prospective studies in age-unselected populations. This review aims to address the knowledge gap pertaining to the use of adjuvant chemotherapy in older patients with resected NSCLC. There are many barriers to use of adjuvant chemotherapy in older adults with NSCLC. The utilization of adjuvant chemotherapy amongst older adults has been slow but is improving. While the elderly may tolerate a lower dose intensity of chemotherapy compared with younger patients, they do garner benefit from adjuvant chemotherapy. There is a lack of a standardized tool to risk-stratify older patients for adjuvant chemotherapy after resection. Geriatric assessment may help guide decision making in the clinical practice setting. The principles of geriatric assessment and commonly employed tools for such assessment will be reviewed. Further, the emerging therapies in adjuvant treatment of lung cancer based on genetic mutations will be discussed.

Lung cancer is the leading cause of cancer associated mortality in the US. Majority of patients with lung cancer are diagnosed with advanced stage cancer and median age at diagnosis is 70 years. The prevalence of comorbidity increases with age and older patients with lung cancer have a particularly high burden, given the common association with smoking. Based on recent data from the US, the vast majority of adults 65 years or older have significant and often multiple comorbid conditions: hypertension (73%), chronic obstructive pulmonary disease (57%), ischemic heart disease (53%), diabetes (32%), congestive cardiac failure (31%), chronic kidney disease (30%), and depression (21%). Since the prognosis in older adults with advanced non-small cell lung cancer (NSCLC) is particularly poor, it is essential to capture the “host” factors that rendermanagement of this disease challenging. Many elderly do not receive treatment for advanced NSCLC. This is largely attributed to poor performance status (PS), a high comorbid disease burden, or a combination thereof. The thoracic medical oncologist typically relies on Eastern Cooperative Oncology Group (ECOG) PS for decision making regarding chemotherapy. The relative contribution of underlying comorbid disease and cancer in defining PS is undetermined. Recent ASCO guidelines allude to the importance of comorbidity (described as multiple chronic

Lung cancer is the leading cause of cancer-associated mortality in the USA. The median age at diagnosis of lung cancer is 70 years, and thus, about one-half of patients with lung cancer fall into the elderly subgroup. There is dearth of high level of evidence regarding the management of lung cancer in the elderly in the three broad stages of the disease including early-stage, locally advanced, and metastatic disease. A major reason for the lack of evidence is the underrepresentation of elderly in prospective randomized clinical trials. Due to the typical decline in physical and physiologic function associated with aging, most elderly do not meet the stringent eligibility criteria set forth in age-unselected clinical trials. In addition to performance status, ideally, comorbidity, cognitive, and psychological function, polypharmacy, social support, and patient preferences should be taken into account before applying prevailing treatment paradigms often derived in younger, healthier patients to the care of the elderly patient with lung cancer. The purpose of this chapter was to review the existing evidence of management of early-stage, locally advanced disease, and metastatic lung cancer in the elderly.

Cell signaling by a highly conserved serine/threonine kinase mammalian target of rapamycin (mTOR) has been shown to play a critical role in cell proliferation. We analyzed the immunohistochemical expression of mTOR, pmTOR and bcl-2 in 55 patients with diffuse large B-cell lymphoma and correlated it with clinical parameters and clinical outcomes. On univariate analysis, higher expression of mTOR was associated with male gender, older age, and higher IPI score. Patients with a high total mTOR score showed a trend toward shorter survival. Based on our results we propose that use of targeted therapy with mTOR inhibitors, in a subset of diffuse large B-cell lymphoma patients may help improve patient survival.

Little is known about complementary medication use among older adults with cancer, particularly those who are receiving chemotherapy. The objective of this study was to evaluate the prevalence of complementary medication use and to identify the factors associated with its use among older adults with cancer.The prevalence of complementary medication use (defined as herbal agents, minerals, or other dietary supplements, excluding vitamins) was evaluated in a cohort of adults aged ≥65 years who were about to start chemotherapy for their cancer. The associations between complementary medication use and patient characteristics (sociodemographics; comorbidities; and functional, nutritional, psychological, and cognitive status), medication use (number of medications and concurrent vitamin use), and cancer characteristics (type and stage) were analyzed.The cohort included 545 patients (mean age, 73 years; range, 65-91 years; 52% women) with cancer (61% stage IV). Seventeen percent of these patients (N = 93) reported using ≥1 complementary medication; the mean number of complementary medications among users was 2 (range, 1-10 medications). Complementary medication use was associated with 1) earlier cancer stage (29% had stage I-II disease vs 17% with stage III-IV disease; odds ratio [OR], 2.05; 95% confidence interval [CI], 1.21-3.49) and 2) less impairment with instrumental activities of daily living (OR, 1.39; 95% CI, 1.12-1.73).Complementary medication use was reported by 17% of older adults with cancer and was more common among those who had less advanced disease (i.e., those receiving adjuvant, potentially curative treatment) and higher functional status. Further studies are needed to determine the association between complementary medication use and cancer outcomes among older adults.

Purpose Older adults are vulnerable to chemotherapy toxicity; however, there are limited data to identify those at risk. The goals of this study are to identify risk factors for chemotherapy toxicity in older adults and develop a risk stratification schema for chemotherapy toxicity. Patients and Methods Patients age ≥ 65 years with cancer from seven institutions completed a prechemotherapy assessment that captured sociodemographics, tumor/treatment variables, laboratory test results, and geriatric assessment variables (function, comorbidity, cognition, psychological state, social activity/support, and nutritional status). Patients were followed through the chemotherapy course to capture grade 3 (severe), grade 4 (life-threatening or disabling), and grade 5 (death) as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events. Results In total, 500 patients with a mean age of 73 years (range, 65 to 91 years) with stage I to IV lung (29%), GI (27%), gynecologic (17%), breast (11%), genitourinary (10%), or other (6%) cancer joined this prospective study. Grade 3 to 5 toxicity occurred in 53% of the patients (39% grade 3, 12% grade 4, 2% grade 5). A predictive model for grade 3 to 5 toxicity was developed that consisted of geriatric assessment variables, laboratory test values, and patient, tumor, and treatment characteristics. A scoring system in which the median risk score was 7 (range, 0 to 19) and risk stratification schema (risk score: percent incidence of grade 3 to 5 toxicity) identified older adults at low (0 to 5 points; 30%), intermediate (6 to 9 points; 52%), or high risk (10 to 19 points; 83%) of chemotherapy toxicity (P < .001). Conclusion A risk stratification schema can establish the risk of chemotherapy toxicity in older adults. Geriatric assessment variables independently predicted the risk of toxicity.

Risk-adaptive therapy for Hodgkin's lymphoma focuses on treatment modifications based on assessment of response. [18F]Fluoro-deoxyglucose positron emission tomography (PET) performed during or after completion of chemotherapy is a strong prognostic factor for eventual treatment outcome. Conceptually, this strategy seeks to increase efficacy and minimize toxicity through the appropriate selection of patients for either therapy escalation (high-risk, PET positive) or de-escalation (low-risk, PET negative). Preliminary evidence with tailoring both chemotherapy (drug selection, number of cycles, and dose) and radiotherapy (omission or inclusion) is varied; however, numerous clinical trials seeking to validate this approach are ongoing. This paper summarizes the available evidence and active protocols involving PET response-adapted therapy for adult (early and advanced stages) Hodgkin's lymphoma.

SUMMARY Crizotinib is now used for ALK-positive adenocarcinoma of the lung. To the best of our knowledge it has not been used concurrently with radiation. We report the first case where a patient safely tolerated crizotinib with concurrent whole-brain radiation therapy for brain metastases in ALK-positive adenocarcinoma of the lung. The patient had a good response to the combination with improved performance status.

Molecular inhibition of the epidermal growth factor receptor (EGFR) is a promising anticancer strategy and monoclonal antibodies (mAbs) to EGFR are undergoing extensive evaluation in preclinical and clinical trials. EGFR is frequently over expressed in many types of human malignancy and may be associated with prognosis, disease stage and survival. Therefore, EGFR represents an attractive target for cancer therapy. Two such agents that inhibit EGFR signaling by interfering with ligand-binding are cetuximab (Erbitux) and panitumumab (Vectibix). Common toxicities of agents targeting the EGFR differ from those associated with traditional chemotherapy. Although rare, cardiac toxicity is a significant complication associated with cetuximab and the clinical spectrum of these toxicities can range from subclinical abnormalities to being catastrophic, life-threatening and sometimes fatal events. This review aims to highlight an important albeit inadequately studied toxicity related to EGFR mAbs. We shall review preclinical and clinical literature to ascertain the etiology, incidence and management of cardiovascular complications of monoclonal antibodies to EGFR. As the potential clinical applications for these agents increase, clinicians using these agents need to remain vigilant regarding cardiovascular complications, especially in view of an aging cancer population.

Purpose The optimal treatment for medically inoperable stage I non–small-cell lung cancer (NSCLC) has not been defined. Patients and Methods Cancer and Leukemia Group B trial 39904 prospectively assessed accelerated, once-daily, three-dimensional radiotherapy for early-stage NSCLC. The primary objectives were to define the maximally accelerated course of conformal radiotherapy and to describe the short-term and long-term toxicity of therapy. Entry was limited to patients with clinical stage T1N0 or T2N0 NSCLC (< 4 cm) and pulmonary dysfunction. The nominal total radiotherapy dose remained at 70 Gy, while the number of daily fractions in each successive cohort was reduced. Results Thirty-nine eligible patients were accrued (eight patients each on cohorts 1 to 4 and seven patients on cohort 5) between January 2001 and July 2005. One grade 3 nonhematologic toxicity was observed in both cohort 3 (dyspnea) and cohort 4 (pain). The major response rate was 77%. After a median follow-up time of 53 months, the actuarial median survival time of all eligible patients was 38.5 months. Local relapse was observed in three patients. Conclusion Accelerated conformal radiotherapy was well tolerated in a high-risk population with clinical stage I NSCLC. Outcomes are comparable to prospective reports of alternative therapies, including stereotactic body radiation therapy and limited resection, with less apparent severe toxicity. Further investigation of this approach is warranted.

Lepirudin is a recombinant hirudin that exerts its anticoagulant effect by direct inhibition of thrombin. Lepirudin is indicated for anticoagulation in patients with heparin-induced thrombocytopenia (HIT) and associated thromboembolic disease to prevent further thromboembolic complications.This review addresses various clinical uses of lepirudin including but not limited to FDA approved indication. The objective is to provide an updated overview of the clinical use and pharmacology of the agent. In addition, we address certain areas of controversy especially pertaining to dosing of lepirudin and its use in different clinical situations.Literature was reviewed using appropriate search terms in Pubmed and Ovid medline databases.Lepirudin continues to be a valuable anticoagulant in the management of HIT. Lepirudin has the highest recommendation in treatment of HIT based on evidence from clinical trials. Minor modifications in dosing over the standard label recommendations may simplify its use and enhance safety.

Cancer is a disease occurring disproportionately in older adults. However, the evidence base regarding how best to care for these patients remains limited due to their underrepresentation in cancer clinical trials. Pragmatic clinical trials represent a promising approach for enhancing the evidence base in geriatric oncology by allowing investigators to enroll older, frailer patients onto cancer clinical trials. These trials are more accessible, less resource intensive, and place minimal additional burden on participating patients. Additionally, these trials can be designed to measure endpoints directly relevant to older adults, such as quality of life, functional independence and treatment tolerability which are often not addressed in standard clinical trials. Therefore, pragmatic clinical trials allow researchers to include patients for whom the treatment will ultimately be applied and to utilize meaningful endpoints. Examples of pragmatic studies include both large, simple trials and cluster randomized trials. These study designs allow investigators to conduct clinical trials within the context of everyday practice. Further, researchers can devise these studies to place minimal burden on the patient, the treating clinicians and the participating institutions. In order to be successful, pragmatic trials must efficiently utilize the electronic medical record for data capture while also maximizing patient recruitment, enrollment and retention. Additionally, by strategically utilizing pragmatic clinical trials to test therapies and interventions that have previously shown efficacy in younger, fitter patients, these trials represent a potential mechanism to improve the evidence base in geriatric oncology and enhance care for older adults with cancer.

OBJECTIVES Anemia is associated with functional disability among older adults in general. However, the relationship between anemia and functional disability has not been well characterized among older adults with cancer. Therefore, we examined the association between anemia and functional disability in patients with cancer aged 65 years or older. PATIENTS AND METHODS We conducted cross-sectional analysis of data derived from a multicenter prospective study of 500 patients with cancer aged 65 years or older. The primary outcome was functional disability at chemotherapy initiation, defined as the need for assistance with at least one instrumental activity of daily living. Anemia (using WHO criteria) was defined as a hemoglobin (Hb) level of less than 12 g/dL in women and less than 13 g/dL in men. Multivariable logistic regression was used to examine the association between anemia and functional disability. RESULTS Among 491 evaluable patients (median age, 73.1 years [range, 65-91 years]), the prevalence of functional disability and anemia was 43% and 51%, respectively. Compared with patients without anemia, patients with anemia were more likely to report functional disability. On multivariable analysis, adjusting for sex, stage, and unintentional weight loss, patients with anemia were more likely to have functional disability (odds ratio, 2.40; 95% CI, 1.61-3.59). CONCLUSIONS Anemia was highly prevalent and independently associated with functional disability in this cohort of older adults with cancer. Given the importance of functional status in cancer treatment decision-making, longitudinal studies evaluating the causal relation between anemia and functional status among older patients with cancer are warranted to evaluate causality.

Purpose To provide evidence-based recommendations to update the American Society of Clinical Oncology guideline on systemic therapy for stage IV non–small-cell lung cancer (NSCLC). Methods An Update Committee of the American Society of Clinical Oncology NSCLC Expert Panel based recommendations on a systematic review of randomized controlled trials from January 2007 to February 2014. Results This guideline update reflects changes in evidence since the previous guideline. Recommendations There is no cure for patients with stage IV NSCLC. For patients with performance status (PS) 0 to 1 (and appropriate patient cases with PS 2) and without an EGFR-sensitizing mutation or ALK gene rearrangement, combination cytotoxic chemotherapy is recommended, guided by histology, with early concurrent palliative care. Recommendations for patients in the first-line setting include platinum-doublet therapy for those with PS 0 to 1 (bevacizumab may be added to carboplatin plus paclitaxel if no contraindications); combination or single-agent chemotherapy or palliative care alone for those with PS 2; afatinib, erlotinib, or gefitinib for those with sensitizing EGFR mutations; crizotinib for those with ALK or ROS1 gene rearrangement; and following first-line recommendations or using platinum plus etoposide for those with large-cell neuroendocrine carcinoma. Maintenance therapy includes pemetrexed continuation for patients with stable disease or response to first-line pemetrexed-containing regimens, alternative chemotherapy, or a chemotherapy break. In the second-line setting, recommendations include docetaxel, erlotinib, gefitinib, or pemetrexed for patients with nonsquamous cell carcinoma; docetaxel, erlotinib, or gefitinib for those with squamous cell carcinoma; and chemotherapy or ceritinib for those with ALK rearrangement who experience progression after crizotinib. In the third-line setting, for patients who have not received erlotinib or gefitinib, treatment with erlotinib is recommended. There are insufficient data to recommend routine third-line cytotoxic therapy. Decisions regarding systemic therapy should not be made based on age alone. Additional information can be found at http://www.asco.org/guidelines/nsclc and http://www.asco.org/guidelineswiki .

Objectives There is a gap in knowledge regarding the rates of utilization of palliative care services (PCS) and acute care services (ACS) among older patients with advanced cancer close to end of life. We analyzed the utilization of these services among older adults (65years and older) and compared them to those in younger adults (40–64years) with advanced cancer. Materials and Methods A retrospective chart review of 567 veterans who died with advanced cancer between 2002 and 2009 and utilized PCS and ACS prior to death was conducted after IRB approval. To assess PCS utilization, we studied the mean duration between day of hospice referral and time of death (DOR) and the mean length of stay with hospice (LoS). The frequency of emergency room visits (ERVLM), hospital admissions (HALM), and ICU admissions (ICULM) in the last month of life was used as a measure for ACS. The differences among older and younger patients were compared using two sample t-tests. Results Older adults had earlier referral to PCS [mean DOR : 47.3 versus 34.5days, p=0.015 ], longer stay with hospice [mean LoS : 32.5 versus 20.2days, p=0.007 ], fewer hospital [ HALM: 0.7 versus 0.9, p=0.043 ], and ICU admissions [ ICULM: 0.1 versus 0.2, p=0.030 ] per patient. The proportion of patients utilizing ER visits [53.5 % versus 59.5%, p=0.173] and hospital admissions [58.6% versus 65.1%, p=0.13] in the last month of life was similar in both age groups with fewer older adults utilizing ICU care [13.2% versus 19.5%, p=0.047]. Conclusion Older patients with cancer are likely to be referred to PCS earlier than younger patients and spend a longer duration with PCS prior to death. However, there continues to be significant utilization of ACS in all patients with advanced cancer. Better understanding of the goals of care in older adults with cancer and education of oncology providers regarding the need to utilize and integrate palliative care services earlier in the course of disease is imperative.

Summary Purpose: To assess the overall and progression-free survival, response rate, and toxicity of combined docetaxel and celecoxib in the treatment of patients with non-small cell lung cancer progressing after initial chemotherapy for advanced disease. Patients and methods: Patients with non-small cell lung cancer and either measurable or evaluable disease experiencing progression after one or more platinum-based chemotherapy regimens given for advanced or metastatic disease, ECOG performance status 0–2, and adequate hematologic and biochemistry parameters were eligible for study inclusion; exclusion criteria included symptomatic brain metastases and full dose anti-coagulation. Therapy consisted of docetaxel 75mg/m 2 every 21 days for a maximum of six cycles and celecoxib 400mg orally twice daily commencing 7 days prior to docetaxel and continuing until disease progression. Results: A total of 41 patients were enrolled of whom 39 were deemed eligible and received at least one course of docetaxel. The mean age of enrolled patients was 60.5 years (range, 44–77); 67% were men and 79% white. All but one patient had an Eastern Clinical Oncology Group (ECOG) performance status of 0 or 1. Most (72%) had been treated with a prior taxane. Overall survival was 11.3 months (95% confidence interval [CI]: 7.9, 15.7) and progression-free survival 19.6 weeks (95% CI: 13.5, 25.0). A response rate of 10.2% (95% CI: 3%, 24%) for all eligible and treated patients was found. Grade 3 or 4 neutropenia occurred in 10/39 patients (25.6%); one death due to neutropenic sepsis occurred. No grade 3 or 4 renal or hepatic toxicities were documented. Conclusion: Treatment with combination celecoxib and docetaxel is a safe regimen with a toxicity profile similar to that of docetaxel alone. Survival data are encouraging compared to historical controls and may prolong time to disease progression compared with single-agent docetaxel.

Purpose: Stage IA (T1N0M0) non-small cell lung cancer (NSCLC) includes all lesions up to 3 cm in diameter. With the use of advanced imaging techniques, smaller pulmonary lesions can be identified. A greater proportion of patients with NSCLC will likely have smaller tumors at presentation in the future. The purpose of this study was to determine the relationship between tumor size, and survival in patients with pathologic stage IA NSCLC. Methods: We conducted a retrospective review of 246 consecutive, surgically treated patients with pathologic stage IA NSCLC. Eligible patients were identified from the tumor registries and pathology records. Follow-up was obtained from the surgical database and primary physicians’ records. Results: Eighty six patients had tumors ≤1.5 cm while 160 patients had tumors 1.6–3.0 cm. The median follow-up time is 60 months. The patients with the tumors ≤1.5 cm had an improved outcome when compared with patients with tumors 1.6–3.0 cm. The 5-year disease free survival (DFS) was 81.5 and 70.9%, respectively, (P=0.03) and the 5-year overall survival was 85.5 and 78.6%, respectively (P=0.05). In the multivariate analysis, tumor size was an independent prognostic factor for survival. Conclusions: Tumor size is a prognostic factor in pathologic stage IA NSCLC treated with adequate surgical resection. Such improvement, not observed in some earlier reports, may represent the effect of improved imaging and pre-operative surgical techniques. This finding requires confirmation in prospective series, but is important since it makes a case for further subdividing T1 lesions in resected NSCLC.

Purpose: We postulate that surgical sampling and pathologic evaluation of lymph nodes of surgical specimens from patients with stage I non–small-cell lung cancer (NSCLC) can have an effect on the time to recurrence and survival of these patients. Patients and Methods: We analyzed data on 442 patients with stage I NSCLC who were treated with surgical resection and some form of lymph node sampling. Associations between total lymph nodes sampled and disease-free survival (DFS) and overall survival (OS) were investigated. The effect of total lymph node stations sampled and the surgical techniques (random lymph node sampling, systematic sampling [SS], or complete mediastinal lymph node dissection [MLND]) on DFS and OS was also studied. Complete MLND and SS were defined as dissection or sampling of levels 4, 7, and 10 for right-sided lesions and levels 5 or 6 and 7 for left-sided lesions. Results: Patients were divided into quartiles on the basis of total number of lymph nodes sampled. Improved DFS and OS were associated with greater number of lymph nodes sampled. SS and MLND were associated with improved survival compared with random lymph node sampling. The total number of lymph nodes sampled maintained strong significance in the multivariate analysis. Conclusion: These results indicate that examining a greater number of lymph nodes in patients with stage I NSCLC treated with resection increases the likelihood of proper staging and affects patient outcome. Such information is important not only for therapy and prognosis of individuals but also for identifying those who may benefit from adjuvant therapy.

9058 Background: Chemotherapy can benefit pts with advanced NSCLC with poor Eastern Cooperative Oncology Group (ECOG) PS, despite an increased toxicity risk vs those with good PS. Safety and efficacy of nab-P/carboplatin ( nab-P/C) induction followed by nab-P monotherapy in pts with advanced NSCLC and ECOG PS 2 are reported. Methods: Chemotherapy-naive pts with histologically/cytologically confirmed stage IIIB/IV NSCLC and ECOG PS 2 received 4 cycles of nab-P 100 mg/m2 d 1, 8 + C AUC 5 d 1 q3w. Pts without disease progression were eligible for monotherapy with nab-P 100 mg/m2d 1, 8 q3w until progression/unacceptable toxicity. Primary endpoint: percentage of pts discontinuing within the first 4 cycles due to treatment-emergent adverse events (TEAEs). Other endpoints: PFS, DCR, OS, ORR, and QoL. Results: Forty pts were treated during the first 4 cycles. Median age was 67.5 y, 60.0% were male, 92.5% were white, and 65.0% had nonsquamous histology. In the primary analysis, 9/40 pts (22.5%) discontinued due to TEAEs during induction. In total, 16/40 pts (40.0%) received nab-P as monotherapy. At the time of data cutoff, 4/40 pts remained on therapy beyond 11 cycles. In all treated pts, the median percentage of per-protocol dose of nab-P was 79.8% and the median nab-P dose intensity was 53.2 mg/m2/week (expected, 66.67 mg/m2/week). See table for other key safety and efficacy data. QoL by LCSS (global) was improved during the study, and similarly EQ-5D-5L dimensions were stable/improved at least once in the majority of pts. Conclusions: This nab-P–based regimen was well tolerated in PS 2 pts with advanced NSCLC. Efficacy outcomes are comparable with previous chemotherapy data with promising QoL. The results support the efficacy and tolerability of this regimen in these pts. NCT02289456. Clinical trial information: NCT02289456. [Table: see text]

10036 Background: Hearing and visual impairment increase the risk of psychological, functional, and cognitive deficits in older adults. However, little is known about their impact in older patients (pts) with cancer. Methods: This is a cross-sectional analysis of 2 prospective studies of pts ≥65 with cancer (Hurria et al. JCO 2011 & 2016) which identified risk factors for chemotherapy (CT) toxicity. Relationships between self-reported hearing/visual impairment (fair, poor or deaf/blind) and the need for assistance in instrumental activities of daily living (IADL, i.e. shopping), or activities of daily living (ADL, i.e. bathing); anxiety; depression and cognitive deficit (>11 on Blessed OMC test) were assessed (adjusted for age, sex, race, education, cancer type/stage, comorbidity, falls & medication). Results: Among 750 pts (median age 72, range 65-94) with solid tumors (28% lung, 27% GI, 30% breast/GYN; 58% stage IV), 28% (n = 213) reported 1 impairment (61% hearing, 39% visual) and 7% (n = 55) both. On multivariate analysis, impaired hearing was associated with IADL dependency, anxiety and depression. Visual impairment was associated with IADL dependency, ADL limitation and depression. Impairment in both was associated with IADL dependency, anxiety, depression and cognitive deficit. Conclusions: Older pts with cancer and hearing/visual impairment are at higher risk of functional, psychological and cognitive deficits. Interventions aimed at improving vision and hearing of older adults with cancer should be studied. [Table: see text]

e21545 Background: A nocebo is an inert substance that causes adverse events. Although previous studies have examined the favorably positive (placebo) effects of an inert substance, few studies have examined negative (nocebo) effects, particularly in older patients who sometimes experience frequent and severe adverse events from cancer therapy. Methods: This study focused on placebo/nocebo-exposed patients who participated in two double-blind, placebo-controlled, cancer therapeutic studies, namely, North Central Cancer Treatment Group (NCCTG) 97-24-51 and American College of Surgeons Oncology Group (ACOSOG) Z9001, with the goal of reporting comparative, age-based adverse event rates. Results: Among the 446 patients who received placebo/nocebo exclusively, 161 were 65 years of age or older at the time of respective trial entry; 5234 adverse events occurred. Unadjusted adverse event rates did not differ significantly between patients 65 years of age or older and those younger: rate ratio (99% confidence intervals (CI): 1.01 (0.47, 2.02) with similar findings for grade 2 or worse adverse events and for all symptom-driven adverse events (for example, pain, loss of appetite, anxiety). Adjustment for sex, ethnicity, baseline performance score, and trial resulted in no significant age-based rate differences in adverse event rates. Similar findings were observed with an age threshold of 70. Conclusions: A nocebo effect appears to occur irrespective of age. This observation suggests that adverse events should be taken no less seriously in older than in younger cancer patients and that education to manage patients’ expectations from cancer therapy might improve tolerability. [Table: see text]

Mechanical valve thrombosis is a rare condition in an adequately anticoagulated patient in the absence of underlying thrombophilia. We report a case of a 76-year-old male with mechanical prosthetic mitral valve thrombosis as the presenting feature of polycythemia vera. The patient was treated with thrombolysis at the time of acute presentation and subsequently maintained on low molecular weight heparin, low-dose aspirin, phlebotomy and hydroxyurea. Hemoglobin, leucocytosis and platelet count were controlled for almost 4 years after which the patient suffered a second, fatal episode in the setting of therapeutic anti-Xa level. This case report highlights the thrombotic risks associated with polycythemia vera. The proposed mechanisms of hypercoagulability in polycythemia vera are reviewed. To the best of our knowledge, mechanical valve thromboses as the presenting feature of polycythemia vera has not been reported previously.

Adjuvant chemotherapy after surgical resection improves outcomes for patients with early-stage non-small cell lung cancer (NSCLC). To the authors' knowledge, there are no published prospective trials to date of adjuvant chemotherapy after surgical resection administered exclusively in older patients. In the current study, the authors sought to evaluate the efficacy of adjuvant chemotherapy in older patients in a Veterans Health Administration cohort.Patients who underwent surgical resection for American Joint Committee on Cancer stages IB to III NSCLC between 2001 and 2011 were analyzed. Data regarding patient demographics and comorbidities, tumor characteristics, and primary treatment were collected. Patients were divided into 2 groups based on age at diagnosis: those aged70 years and those aged ≥70 years. The primary exposure was use of adjuvant chemotherapy. A Cox proportional hazards model was used to estimate the significance of patient characteristics. Survival curves were estimated using the Kaplan-Meier method and group comparisons were performed using the log-rank test.The analysis included 7593 patients who underwent surgical resection for stage IB to stage III NSCLC. Among these, 2897 patients (38%) were aged ≥70 years. The percentage of older patients who received adjuvant chemotherapy was approximately one-half that of younger patients who did so (15.3% vs 31.6%; P.0001). Carboplatin-based doublets were used most often in all patients (64.6%). Both younger patients (hazard ratio, 0.79; 95% confidence interval, 0.72-0.86) and older patients (hazard ratio, 0.81; 95% confidence interval, 0.71-0.92) were found to have a lower risk of death with receipt of adjuvant chemotherapy.Older patients derive a similar magnitude of benefit from adjuvant chemotherapy as younger patients and therefore adjuvant chemotherapy should not be withheld based on age alone.

Radiation-induced salivary gland tumors are well described in the literature, with mucoepidermoid cancer being the most common histologic entity. Epithelial-myoepithelial carcinoma is a rare tumor accounting for1% of all tumors in the salivary glands.We describe the first case of radiation-induced epithelial-myoepithelial carcinoma in the English-language medical literature. A 48-year-old man presented with right-sided mandibular pain and trismus, 25 years after mantle-field radiation therapy (RT) for Hodgkin lymphoma. He underwent excision of a right submandibular mass, which revealed a diagnosis of epithelial-myoepithelial carcinoma. Although typically a low-grade tumor, the histology revealed extensive necrosis and high mitotic activity. The patient required multiple resections and adjuvant therapy after multiple recurrences over a 4-year period.Reports of epithelial-myoepithelial carcinoma are relatively rare and this case highlights the importance of long-term follow-up and increased awareness of the risks of salivary gland tumors in this population.

Lung cancer is a disease of the elderly. In older patients, the management of a malignancy as complex and potentially as lethal as lung cancer is challenging. Despite the fact that a large proportion of patients with non–small-cell lung cancer are elderly, information remains scant on how best to treat these patients. The goal of this review is to discuss the published literature and to provide guidance on how to treat elderly patients within three broad stages: (1) metastatic cancer, (2) early-stage cancer after surgery, and (3) locally advanced inoperable cancer. Because decisions on how and when to prescribe systemic treatment can be particularly difficult, this review focuses heavily on chemotherapy-related treatment decisions with some discussion of emerging data on the use of the comprehensive geriatric assessment.

Studies point to a direct association between social support and better cancer outcomes. This study examined whether baseline social support is associated with better survival and fewer chemotherapy-related adverse events in older, early-stage breast cancer patients.This study is a pre-planned secondary analysis of CALGB 49907/Alliance A171301, a randomized trial that compared standard adjuvant chemotherapy versus capecitabine in breast cancer patients 65 years of age or older. A subset reported on the extent of their social support with questionnaires that were completed 6 times over 2 years.The median age of this 331-patient cohort was 72 years (range: 65, 90); 179 (55%) were married, and 210 (65%) lived with someone. One hundred forty-five patients (46%) described a social network of 0-10 people; 110 (35%) of 11-25; and 58 (19%) of 26 or more. The Medical Outcomes Study (MOS) social support survey revealed that the median scores (range) for emotional/informational, tangible, positive social interaction, and affectionate social support were 94 (3, 100), 94 (0, 100), 96 (0, 100), and 100 (8, 100), respectively. Social support scores appeared stable over 2 years and higher (more support) than in other cancer settings. No statistically significant associations were observed between social support and survival and adverse events in multivariate analyses. However, married patients had smaller tumors, and those with arthritis reported less social support.Although social support did not predict survival and adverse events, the exploratory but plausible inverse associations with larger tumors and arthritis suggest that social support merits further study.

Patients who are able to care for themselves but are unable to perform most work-related activities are considered to have a poor performance status (PS). Individuals who fulfill these criteria constitute a significant proportion of all patients with lung cancer. Patients with lung cancer and a poor PS, irrespective of age, have an increased incidence of adverse effects with therapy and poorer outcomes. Thus, although these individuals must be treated differently, data on optimal approaches for these patients are lacking, because this cohort is underrepresented in conventional clinical trials due to enrollment restrictions. This article presents the available evidence on the treatment of this group of patients with lung cancer. Although patients with PS 2 have worse overall outcomes than those with good PS, a selected proportion may still benefit from standard therapy. Further trials are needed to identify optimal strategies to treat this group of patients with lung cancer.

Background The mammalian target of rapamycin (mTOR) pathway regulates many major cellular processes and is implicated in an increasing number of neoplasms, including lymphoma. Patients and Methods We correlated immunohistochemical expression of mTOR with germinal center and nongerminal center phenotype, B cell lymphoma-2 (bcl-2) and cellular homolog of the retroviral v-myconcogene (c-myc) expression, and International Prognostic Index (IPI) score in 31 patients with diffuse large B-cell lymphoma (DLBCL). Results Virtually all patients in our study with high mTOR scores had a germinal center phenotype. Furthermore within the germinal center subgroup, patients with high mTOR scores were associated with higher IPI scores ( P Conclusion Based on our results we propose that within the category of germinal center phenotype of DLBCL, mTOR expression might help identify a subset of patients with potentially more aggressive tumors who might benefit from use of targeted therapy using mTOR inhibitors.

In older men with prostate cancer, aging is associated with reduced anxiety and increased depression. The purpose of this study was to examine the association among age, anxiety, and depression in a cohort of older adults receiving chemotherapy.This is a secondary analysis of a prospective longitudinal study investigating chemotherapy toxicity in older adults with cancer. Baseline data (pre-chemotherapy) included: age, sociodemographics, tumor and treatment factors, functional status, comorbidities, psychological state (measured by the Hospital Anxiety and Depression Scale), and social support. Univariate and multiple regression analyses were conducted to test the relationship between age, anxiety, and depression.The average age of the 500 patients (56% females) was 73.1. The majority had late stage disease: 22% Stage III and 61% stage IV. Clinically significant depression was reported in 12.6%. Clinically significant anxiety was reported in 20.9%. In univariate analyses, there was no association between anxiety and age, or depression and age. In multivariable analyses, older age (p=0.05) was associated with decreased anxiety, as well as lack of social support (p0.01) and increased number of comorbidities (p0.01). In multivariable analysis, depression was associated with lack of social support (p0.01), increased number of comorbidities (p0.01), and advanced stage (p0.01).This study supports previous research that anxiety decreases with age in older adults with cancer. However, depression remained constant with increasing age. Greater resources and attention to identifying and treating the psychological sequelae of cancer in older adults are warranted.

Approximately 60% of cancer incidence, and 70% of cancer mortality, occurs in older adults.1 Unfortunately, cancer care is hampered by a lack of data regarding the risks and benefits of cancer therapy in older adults.2-5 Older adults have been underrepresented on clinical trials, and geriatric issues traditionally have not been considered in oncology study design. The need for evidence-based recommendations for healthy and vulnerable or frail older adults is critical, as life expectancy increases and aging baby boomers are expected to double the US population that is aged 65 years and older by 2030.6 The challenge imminently facing the field of medical oncology is that there are not enough oncologists or geriatricians available today to care for this growing population of older adults with cancer. Further, there is little crosstalk between these fields that would lead to the development and design of pertinent research studies. To bridge this gap, the American Society of Clinical Oncology and the John A. Hartford Foundation supported 10 training programs in geriatrics and oncology from 2001 to 2006. Twenty-eight geriatric oncology trainees participated in the combined fellowship program at these institutions. Several other individuals have trained sequentially in geriatrics and oncology or have developed a research interest in the field of geriatric oncology. These investigators are now entering junior faculty positions. Their training provides them with the skills to design and develop research in the field of geriatric oncology and to forge collaborations with internal medicine, geriatrics, and oncology. These new researchers are positioned not only to conduct research studies regarding the questions that are crucial to geriatric oncology, but also to promote the enrollment of older adults in cancer clinical trials. However, the progress of these young investigators who are working at the intersection of geriatrics and oncology may be hampered for several reasons. First, because of the multidisciplinary nature of their work, it may be difficult for them to find mentors at their own institutions who share their interest in the older patient with cancer. Second, the investigators are geographically dispersed. Multisite collaborations represent a challenge for all investigative teams, but this is particularly so for those new to an underrepresented field in cancer research. Third, many academic medical centers tend to attract a relatively young patient population. This can make it more difficult to perform geriatric oncology studies and expeditiously meet the accrual goal of older patients at a single institution. In aggregate, these barriers may limit the ability of these uniquely trained individuals to obtain grant funding and to develop and to accrue patients on to interdisciplinary clinical trials that evaluate and treat older patients with malignancies. Presently, there is no direct mechanism for junior faculty in geriatric oncology to develop collaborations and mentoring relationships with others in the field. To address this need, junior investigators in geriatric oncology and a senior mentoring team assembled in Duarte, California, in April 2007 for the first Cancer and Aging Research Group Meeting. The meeting was collaboratively supported by the John A. Hartford Foundation and the City of Hope. The goals of this meeting were to do the following three things: provide feedback on geriatric oncology research proposals, discuss approaches to obtain funding for geriatric oncology research, and encourage collaboration/networking among junior faculty in geriatric oncology. Two days of discussion generated and fine-tuned clinical research proposals that were considered high priority in geriatric oncology. At the meeting, the junior investigators presented concepts and ongoing geriatric oncology research for critique by both their peers and senior mentors. In addition, collaborative ties were developed among junior and senior investigators with similar research interests. Three critical areas of research in geriatric oncology were deemed high priority by both junior and senior investigators. These include the assessment of physiologic age, pharmacology of cancer therapy in older adults, and cancer survivorship issues pertinent to older adults. At the end of the conference, several practical recommendations for clinical trial design emerged. The consensus of the Cancer and Aging Research Group was that a geriatric assessment, as an assessment of physiologic age, should be included in all clinical trials that involve patients aged 70 years and older. Incorporating a geriatric assessment in clinical trials of older adults can strengthen the clinical trial design in the following ways: A geriatric assessment captures competing causes of morbidity and mortality, which can be accounted for in the data analysis7-17; a geriatric assessment would identify factors other than chronologic age that predict the toxicity risk with cancer therapy and point the way to interventions that could improve treatment tolerance; and incorporation of a geriatric assessment at sequential time points during and after therapy would provide insight into the impact of cancer therapy on an older adult's functional status, comorbidity, psychological state, and cognitive function. The second area of research in geriatric oncology that was highlighted was the need for studies that evaluate the pharmacology of new cancer therapies in older adults. Age-related changes in renal and hepatic function may impact the pharmacokinetics and pharmacodynamics of cancer therapies. In addition, the impact of drug interactions and comorbid medical conditions on the risk of toxicity needs to be studied. Novel dosing regimens to minimize the risk of myelosuppression should be explored, and studies of supportive care measures or other interventions to minimize toxicity are of high research priority. The third area of research that was highlighted was the long-term impact of cancer therapy on cancer survivors. One of the main goals of geriatric medicine is maintenance of function and prolongation of active life expectancy. Quality active life expectancy is dependent on an individual's function, including physical and cognitive performance. This goal is of special concern for older patients with cancer, as some complications of cancer chemotherapy treatment, including cardiomyopathy, neuropathy, or cognitive decline, may have long-term effects on independence and functional status. The interaction between comorbid medical illnesses and the long-term impact of cancer therapy has also been understudied. Although several studies on the potential impact of cancer therapy on cognitive function have emerged,18-21 few studies have addressed the impact of cancer therapy in older adults in general or in those with pre-existing cognitive impairment.22,23 The consensus of the Cancer and Aging Research Group was that research on the long-term impact of cancer therapy on the functional and cognitive status of older cancer survivors is of high priority. A growing number of investigators have developed a clinical and research focus on the issues that face older adults with cancer. In this report, we highlight an approach to help these individuals gain traction as they transition from their training to become independent clinical investigators. The newly formed Cancer and Aging Research Group of junior investigators, mentored by a senior investigator team, has adopted the mission of developing and fostering collaborative research among junior investigators interested in cancer and aging to address the specific issues that face older adults with cancer. Fostering collaboration and mentoring individuals committed to this cause will substantially further the field of geriatric oncology. The Cancer and Aging Research Group has successfully competed for a grant from the Association of Specialty Professors to the American Society of Clinical Oncology Foundation to help support the next meeting of this research group. Its members currently are collaborating on prospective studies designed to address areas of high research priority in geriatric oncology. Additional funding sources are being sought to support the ongoing mentoring and collaborative research efforts of junior investigators in cancer and aging.