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PURPOSE Eight percent of young-adult childhood cancer survivors meet criteria for frailty, an aging phenotype associated with poor health. In the elderly general population, frailty is associated with neurocognitive decline; this association has not been examined in adult survivors of childhood cancer. METHODS Childhood cancer survivors 18-45 years old (≥ 10 years from diagnosis) were clinically evaluated for prefrailty or frailty (respectively defined as ≥ 2 or ≥ 3 of: muscle wasting, muscle weakness, low energy expenditure, slow walking speed, and exhaustion [Fried criteria]) and completed neuropsychologic assessments at enrollment (January 2008-June 2013) and 5 years later. Weighted linear regression using inverse of sampling probability estimates as weights compared differences in neurocognitive decline in prefrail and frail survivors versus nonfrail survivors, adjusting for diagnosis age, sex, race, CNS–directed therapy (cranial radiation, intrathecal chemotherapy, and neurosurgery), and baseline neurocognitive performance. RESULTS Survivors were on average 30 years old and 22 years from diagnosis; 18% were prefrail and 6% frail at enrollment. Frail survivors declined an average of 0.54 standard deviation (95% CI, −0.93 to −0.15) in short-term verbal recall, whereas nonfrail survivors did not decline (β = .22; difference of βs = −.76; 95% CI, −1.19 to −0.33). Frail survivors declined more than nonfrail survivors on visual-motor processing speed (β = −.40; 95% CI, −0.67 to −0.12), cognitive flexibility (β = −.62; 95% CI, −1.02 to −0.22), and verbal fluency (β = −.23; 95% CI, −0.41 to −0.05). Prefrail and frail survivors experienced greater declines in focused attention (prefrail β = −.35; 95% CI, −0.53 to −0.17; frail β = −.48; 95% CI, −0.83 to −0.12) compared with nonfrail survivors. CONCLUSION Over approximately 5 years, prefrail and frail young-adult survivors had greater declines in cognitive domains associated with aging and dementia compared with nonfrail survivors. Interventions that have global impact, designed to target the mechanistic underpinnings of frailty, may also mitigate or prevent neurocognitive decline.

Long-term survivors of childhood Hodgkin lymphoma (HL) experience a high burden of chronic health morbidities. Correlates of neurocognitive and psychosocial morbidity have not been well established. A total of 1760 survivors of HL (mean ± SD age, 37.5 ± 6.0 years; time since diagnosis, 23.6 ± 4.7 years; 52.1% female) and 3180 siblings (mean age, 33.2 ± 8.5 years; 54.5% female) completed cross-sectional surveys assessing neurocognitive function, emotional distress, quality of life, social attainment, smoking, and physical activity. Treatment exposures were abstracted from medical records. Chronic health conditions were graded according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events version 4.3 (1 = mild, 2 = moderate, 3 = severe/disabling, and 4 = life-threatening). Multivariable analyses, adjusted for age, sex, and race, estimated relative risk (RR) of impairment in survivors vs siblings and, among survivors, risk of impairment associated with demographic, clinical, treatment, and grade 2 or higher chronic health conditions. Compared with siblings, survivors had significantly higher risk (all, P < .05) of neurocognitive impairment (eg, memory, 8.1% vs 5.7%), anxiety (7.0% vs 5.4%), depression (9.1% vs 7%), unemployment (9.6% vs 4.4%), and impaired physical/mental quality of life (eg, physical function, 11.2% vs 3.0%). Smoking was associated with a higher risk of impairment in task efficiency (RR, 1.56; 95% confidence interval [CI], 1.02-2.39), emotional regulation (RR, 1.84; 95% CI, 1.35-2.49), anxiety (RR, 2.43; 95% CI, 1.51-3.93), and depression (RR, 2.73; 95% CI, 1.85-4.04). Meeting the exercise guidelines of the Centers for Disease Control and Prevention was associated with a lower risk of impairment in task efficiency (RR, 0.70; 95% CI, 0.52-0.95), organization (RR, 0.60; 95% CI, 0.45-0.80), depression (RR, 0.66; 95% CI, 0.48-0.92), and multiple quality of life domains. Cardiovascular and neurologic conditions were associated with impairment in nearly all domains. Survivors of HL are at elevated risk for neurocognitive and psychosocial impairment, and risk is associated with modifiable factors that provide targets for interventions to improve long-term functional outcomes.

OBJECTIVE This study used childhood cancer survivors as a novel model to study whether children who experience central nervous system (CNS) injury are at higher risk for neurocognitive impairment associated with subsequent late onset chronic health conditions (CHCs). METHODS Adult survivors of childhood cancer (n = 2,859, ≥10 years from diagnosis, ≥18 years old) completed a comprehensive neurocognitive battery and clinical examination. Neurocognitive impairment was defined as age-adjusted z score

Purpose: Pulmonary dysfunction is a prevalent and potentially debilitating late effect of pediatric cancer treatment. We postulated that age, as a surrogate for respiratory developmental status, might be associated with vulnerability to pulmonary injury. Materials and Methods: Sixty-one children treated with lung radiation at our institution who had undergone a pulmonary function test (PFT) between 1995 and 2016 were analyzed. Data collection included age at diagnosis and treatment, radiation dose and location, spirometry, and plethysmography results. PFTs were normalized according to age, sex, height, and ethnicity, and transformed into standardized z-scores. Obstructive disease was defined as forced expiratory volume in 1 second z score/forced vital capacity z score < −1.645, restrictive as total lung capacity z score 13. Compared with patients >13 years, those .05). Conclusions: PFT abnormalities were common among our cohort of childhood cancer survivors treated with lung radiation. Younger age at treatment is associated with an increased risk of developing pulmonary dysfunction, presumably owing to developmental immaturity.

Purpose To quantify the impact of diabetes on the trajectory of cancer-related fatigue (CRF) from pre-chemotherapy to 6 months post-chemotherapy for patients with breast cancer compared to non-cancer controls.Methods This was a secondary analysis from a nationwide prospective longitudinal study of female patients with breast cancer undergoing chemotherapy and age-matched women without cancer (controls). CRF was measured using the Multidimensional Fatigue Symptom Inventory (MFSI) pre-, post-, and 6-months post-chemotherapy in patients; controls were assessed at equivalent time points. Diabetes status was obtained at baseline. Repeated measures mixed models estimated the association between CRF and diabetes controlling for cancer (y/n), body mass index, exercise and smoking habits, baseline anxiety and depressive symptoms, menopausal status, marital status, race, and education.Results A total of 439 patients and 235 controls (age: 52.8±10.5 years) had available data on diabetes status. Diabetes was twice as prevalent among patients as controls (11.6% vs. 6.8%). Patients had worse fatigue than controls throughout treatment (p Diabetes was associated with worse CRF with a clinically meaningful difference of 4.7±1.7 points on the fatigue measure in all participants (p=0.009) and patients alone (p=0.030). For MFSI subdomains, diabetes was associated with worse general (p=0.002), physical (p=0.005), and mental fatigue (p=0.025) but not worse emotional fatigue or vigor (p>0.14) among patients. Conclusions Diabetes was twice as prevalent in women with breast cancer compared to controls, and diabetes was associated with more severe CRF in patients before and after chemotherapy and at 6 months post-chemotherapy. Interventions that address diabetes management may also help address CRF during chemotherapy treatment

Purpose: Clinical trials of venetoclax reported negligible rates of clinical tumor lysis syndrome (TLS) in patients with chronic lymphocytic leukemia (CLL) when using an extended dose escalation schedule. We aimed to understand TLS prophylaxis, rates of select adverse events (AE), and impact of dosing modifications in routine clinical practice. Experimental Design: This retrospective cohort study included 297 CLL venetoclax-treated patients outside of clinical trials in academic and community centers. Demographics, baseline disease characteristics, venetoclax dosing, TLS risk and prophylaxis, and AEs were collected. Results: The group was 69% male, 96% had relapsed/refractory CLL, 45% had deletion chromosome 17p, 84% had unmutated IGHV, 80% received venetoclax monotherapy, and median age was 67. TLS risk was categorized as low (40%), intermediate (32%), or high (28%), and 62% had imaging prior to venetoclax initiation. Clinical TLS occurred in 2.7% of patients and laboratory TLS occurred in 5.7%. Pre-venetoclax TLS risk group and creatinine clearance independently predict TLS development in multivariable analysis. Grade 3/4 AEs included neutropenia (39.6%), thrombocytopenia (29.2%), infection (25%), neutropenic fever (7.9%), and diarrhea (6.9%). Twenty-two patients (7.4%) discontinued venetoclax due to an AE. Progression-free survival was similar regardless of number of dose interruptions, length of dose interruption, and stable venetoclax dose. Conclusions: These data provide insights into current use of venetoclax in clinical practice, including TLS rates observed in clinical practice. We identified opportunities for improved adherence to TLS risk stratification and prophylaxis, which may improve safety.

BACKGROUND: As oral targeted agents, such as ibrutinib, become more widely used understanding the impact of suboptimal dosing on overall and progression-free survival outside of clinical trials is imperative. METHODS: Data on ibrutinib discontinuation, dose reductions and treatment interruptions were collected on 170 non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL n=115, 64%) patients treated with ibrutinib at a single institution. Ibrutinib dose adherence was calculated as the proportion of days in which ibrutinib was administered out of the total number of days ibrutinib was prescribed in the first 8 weeks. Kaplan-Meier curves and log-rank tests were used to compare conditional survival outcomes beyond 8 weeks in patients ≥80% dose adherence and patients 1 week had worse PFS (p=0.047) but not OS (p=0.577). CONCLUSION: In this observational study, NHL and CLL patients demonstrated poor outcomes after discontinuing ibrutinib for disease progression. The inferior survival related to suboptimal dose adherence of ibrutinib was predominantly due to early dose reduction. These data confirm poor survival in CLL and lymphoma patients alike after ibrutinib discontinuation and support recommendations for full dose at treatment initiation.

The cumulative burden of chronic health conditions as childhood cancer survivors transition to adult health care and insurance systems is unknown. We estimated the cumulative burden (N = 4612 survivors, 625 controls) in the St. Jude Lifetime Cohort. At 18 and 26 years old, survivors experienced (per 100 individuals) an average of 22.3 (95% confidence interval [CI]: 17.2-27.4) and 40.3 (95% CI: 34.8-45.8) disabling conditions versus 3.5 (95% CI: 2.0-5.0) and 5.7 (95% CI: 3.7-7.7) in controls, and 128.7 (95% CI: 119.5-137.8) and 240.5 (95% CI: 229.9-251.0) lower severity conditions versus 12.4 (95% CI: 8.9-16.0) and 51.3 (95% CI: 43.1-59.4) in controls. Survivors experience a high cumulative burden at key health care transition ages, underscoring the need to optimize access to care.

PURPOSE: Fatigue and anxiety are common and significant symptoms reported by cancer patients. Few studies have examined the trajectory of multidimensional fatigue and anxiety, the relationships between them and with quality of life. METHODS: Breast cancer patients (n=580) from community oncology clinics and age-matched controls (n=364) completed fatigue and anxiety questionnaires prior to chemotherapy (A1), at chemotherapy completion (A2), and six months post-chemotherapy (A3). Linear mixed models (LMM) compared trajectories of fatigue /anxiety over time in patients and controls and estimated their relationship with quality of life. Models adjusted for age, education, race, BMI, marital status, menopausal status, and sleep symptoms. RESULTS: Patients reported greater fatigue and anxiety compared to controls at all time points (p’s

The increasing number of long-term survivors of childhood/adolescent cancer are at-risk for premature death resulting from cancer treatment exposures. To better understand the implications of late mortality, we estimated and characterized the magnitude and temporal patterns of annual excess deaths following childhood/adolescent cancers diagnosed in 1975-2016 in the US using SEER 9 registries. We demonstrate for several tumor types that, despite decreasing excess deaths

Phosphoinositide-3-kinase (PI3K) inhibitors have efficacy in lymphoid malignancies; however, inflammatory and infectious toxicities can compromise the treatment course. An improved understanding of these toxicities will guide clinical use and further development. We evaluated the occurrence of treatment-related adverse events (AEs) in a retrospective review of 79 patients treated in standard fashion with PI3K inhibitor monotherapy or with anti-CD20 monoclonal antibodies or as part of a novel combination regimen. Patients treated with a novel combination were at a higher risk of developing a severe AE compared to those treated with standard therapy (HR 1.89, 95% CI 1.02, 3.49

Family and migration studies suggest a genetic risk of developing chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL). We hypothesized that CLL patients have an increased risk of additional clonally unrelated B-cell malignancies. To test this, we studied 467 CLL patients (2743 person-years (PYs)) at a single institution over 17 years. The incidence rate (IR) of any additional B-cell lymphoid malignancy was 10.9 per 1000 PYs (

Cancer-related cognitive impairment (CRCI) has not been objectively assessed in chronic lymphocytic leukemia (CLL). It is currently unclear how much of CRCI is attributable to disease, treatment, or both. We used CLL as a novel model to study the differential roles of disease and treatment in CRCI. 150 CLL patients (100 treatment-naïve and 50 chemotherapy-treated) including 84 patients with higher-risk of CLL progression completed objective neuropsychological tests. Sociodemographic-adjusted linear regression models examined cognitive outcomes in relation to risk and treatment. Higher-risk patients recalled 2 fewer words on a memory task (β=−1.8, 95%CI-3.3,−0.3) and took 15 seconds longer on an executive function task (β=15.4, 95%CI 3.1,27.6) than lower-risk patients, independent of treatment. Treated patients reported greater cognitive difficulties than treatment-naive patients (β=−6.1, 95%CI-10.1,−2.2) but did not perform worse on objective measures. Higher-risk patients experienced impairments in executive function and memory suggesting that disease biology contributes to CRCI independent of treatment.

Venetoclax is a BCL2 inhibitor approved for 17p-deleted relapsed/refractory chronic lymphocytic leukemia with activity following kinase inhibitors. We conducted a multicenter retrospective cohort analysis of patients with chronic lymphocytic leukemia treated with venetoclax to describe outcomes, toxicities, and treatment selection following venetoclax discontinuation. A total of 141 chronic lymphocytic leukemia patients were included (98% relapsed/refractory). Median age at venetoclax initiation was 67 years (range 37-91), median prior therapies was 3 (0-11), 81% unmutated IGHV, 45% del(17p), and 26.8% complex karyotype (≥ 3 abnormalities). Prior to venetoclax initiation, 89% received a B-cell receptor antagonist. For tumor lysis syndrome prophylaxis, 93% received allopurinol, 92% normal saline, and 45% rasburicase. Dose escalation to the maximum recommended dose of 400 mg daily was achieved in 85% of patients. Adverse events of interest included neutropenia in 47.4%, thrombocytopenia in 36%, tumor lysis syndrome in 13.4%, neutropenic fever in 11.6%, and diarrhea in 7.3%. The overall response rate to venetoclax was 72% (19.4% complete remission). With a median follow up of 7 months, median progression free survival and overall survival for the entire cohort have not been reached. To date, 41 venetoclax treated patients have discontinued therapy and 24 have received a subsequent therapy, most commonly ibrutinib. In the largest clinical experience of venetoclax-treated chronic lymphocytic leukemia patients, the majority successfully completed and maintained a maximum recommended dose. Response rates and duration of response appear comparable to clinical trial data. Venetoclax was active in patients with mutations known to confer ibrutinib resistance. Optimal sequencing of newer chronic lymphocytic leukemia therapies requires further study.

Cancer-related cognitive impairment (CRCI) is often related to chemotherapy. Increased chronic inflammation is believed to play a key role in the development of CRCI related to chemotherapy but studies assessing this hypothesis specifically in patients receiving chemotherapy are rare.We assessed several cognitive domains using the Cambridge Neuropsychological Test Automated Battery (CANTAB) in twenty-two breast cancer patients currently receiving chemotherapy. We also measured inflammatory cytokine and receptor (MCP-1, TNF-α, sTNFRI, sTNFRII) concentrations in patient sera using Luminex assays. These concentrations were log-transformed to obtain a normal distribution. Associations between log-transformed cytokines and cognition were evaluated using Pearson correlations and linear regression, taking into account relevant covariates.Increased concentrations of sTNFRI and sTNFRII were associated with poorer performance on the CANTAB Delayed Matching to Sample (DMS, tests visual memory). Increasing sTNFRI levels were negatively correlated with DMS percent correct (r=-0.47, p=0.029) and DMS percent correct after a 12 second (s) delay (r=-0.65, p=0.001). Increasing levels of sTNFRII negatively correlated with DMS percent correct after 12s delay (r=-0.57, p=0.006). After controlling for relevant demographic (i.e. age, education) and clinical variables (i.e. disease stage, regimen type), we found that increased sTNFRI remained significantly related to decline on the DMS at the 12s delay (p=0.018).This preliminary study shows a significant association between higher sTNFRI and lower scores on the short-term visual memory delayed match to sample test in breast cancer patients receiving chemotherapy, supporting the hypothesis that sTNFRI is involved in CRCI.

Background: Long-term survivors of childhood Hodgkin lymphoma (HL) are at significant risk for cardiovascular, pulmonary, and endocrine morbidity in addition to subsequent cancers. Emerging evidence suggests that HL survivors may also experience persistent neurocognitive impairment, however the prevalence of neurocognitive impairment has not been well characterized. Further, little work has been done to examine how specific treatments or comorbidities are associated with these impairments. Methods: The current study included 1,760 survivors (52.0% female, mean[sd] 37.5 [6.0] years old, 23.6 [4.7] years from diagnosis) of childhood Hodgkin lymphoma and 3,180 sibling controls (54.5% female, 33.2 [8.5] years old) from the Childhood Cancer Survivor Study. Participants completed questionnaires assessing four domains of neurocognitive impairment (task efficiency, emotional regulation, organization, and memory). Impairment for each domain was defined as a score worse than the 90th percentile of community controls. Treatment exposures were abstracted from the medical record. Second malignancies (SMN) were self-reported and subsequently confirmed by pathology findings or medical record review. Chronic health conditions were self-reported and systematically graded according to the NCI CTCAE v4.3 (Grade 1 mild, Grade 2 moderate, Grade 3 severe/disabling, Grade 4 life-threatening). Generalized estimating equations were used to calculate risk of impairment in survivors compared with siblings adjusted for age, sex, and race. Among HL survivors, multivariable log-binomial regression was used to calculate risk of impairment associated with demographic, clinical, and treatment factors. Separate models examined risk associated with Grade 2+ chronic health conditions adjusted for age, sex, and race. Results: 10.8% of HL survivors reported impaired task efficiency (vs. 7.7% in siblings), 16.6% emotional regulation (vs. 11.5% in siblings), 12.1% organization (vs. 10.3% in siblings), and 8.1% memory (vs. 5.7% in siblings). Compared with siblings, survivors reported significantly higher risk of impairment in each of the four neurocognitive domains after adjusting for age, sex, and race (Table). Female survivors had elevated risk of impairment on emotional regulation (RR [95%CI] 1.4 [1.1,1.9)) and memory (2.0 [1.3,3.0]). Compared with white survivors (91.8% of the population), non-white survivors had higher risk of impairment in task efficiency (2.1 [1.2, 3.5]) and emotional regulation (1.7 [1.0,2.7]). Current smokers (12.3%) had higher risk of impairment in task efficiency (1.9 [1.2, 3.1]), emotional regulation (2.5 [1.7,3.7]), and memory (1.7 [1.0,3.0]). Having a late-relapse (>5 years from diagnosis) or a second malignancy (20.0%) was associated with elevated risk of impairment in task efficiency (1.6 [1.06,2.3]). While not statistically significant, anthracycline exposure (39.8%) was associated with higher risk of impairment in task efficiency (1.3 [0.7,2.2]) and memory (1.6 [0.9,3.0]). No statistically significant associations were noted for bleomycin, corticosteroids, or chest radiation. HL survivors with pulmonary morbidity (8.5%) had a higher risk of impairment on task efficiency (1.9 [1.2,3.0]) compared to those without. Cardiovascular conditions (32.9%) were associated with elevated risk of impairment in all domains (RR range from 1.5 to 2.1, all p Conclusions: Survivors experienced significantly more neurocognitive impairment compared to sibling controls. Among survivors, potentially modifiable risk factors such as smoking and chronic health conditions were associated with neurocognitive impairment while treatment exposures showed little association. Mitigation or prevention of smoking and chronic health conditions may improve neurocognitive functioning in HL survivors Table Disclosures No relevant conflicts of interest to declare.

10045 Background: Survivors of childhood cancer have functional limitations and health-related morbidity consistent with an accelerated aging phenotype. We characterized aging using a Deficit Accumulation Index (DAI) which examines the accumulation of multiple aging-related deficits readily available from medical records and self-report. DAI’s are used as surrogates of biologic aging and are validated to predict mortality in adult cancer patients. Methods: We included childhood cancer survivors (N = 3,758, mean age 30 [SD 8], 22 [9] years post diagnosis, 52% male) and community controls (N = 575, mean age 34 [10] 44% male) who completed clinical assessments and questionnaires and who were followed for mortality through December 31st, 2018 (mean follow-up 6.1 [3.1] years). Using the initial SJLIFE clinical assessment, a DAI score was generated as the proportion of deficits out of 44 items related to aging, including chronic conditions (e.g. hearing loss, hypertension), psychosocial and physical function, and activities of daily living. The total score ranged 0 to 1; scores > 0.20 are robust, while moderate and large clinically meaningful differences are 0.02 and 0.06, respectively. Linear regression compared the DAI in survivors and controls with an age*survivor/control interaction and examined treatment associations in survivors. Cox-proportional hazards models estimated risk of death associated with DAI. All models were adjusted for age, sex, and race. Results: Mean [SD] of DAI was 0.17 [0.11] for survivors and 0.10 [0.08] for controls. 32% of survivors had a DAI above the 90th percentile of the control distribution (p < 0.001). After adjustment for covariates, survivors had a statistically and clinically meaningfully higher DAI score than controls (β = 0.072 95%CI 0.062, 0.081; p < 0.001). When plotted against age, the adjusted DAI at the average age of survivors (30 years) was 0.166 (95% CI 0.160,0.171), which corresponded to 60 years of age in controls, suggesting premature aging of 30 years. The mean difference in DAI between survivors and controls increased with age from 0.06 (95% CI 0.04, 0.07) at age 20 to 0.11 (95% CI 0.08, 0.13) at age 60, consistent with an accelerated aging phenotype (p = 0.014). Cranial radiation, abdominal radiation, cyclophosphamide, platinum agents, neurosurgery, and amputation were each associated with a higher DAI (all p≤0.001). Among survivors, a 0.06 increase in DAI was associated with a 41% increased risk of all-cause mortality (HR 1.41 95%CI 1.32, 1.50; p < 0.001). Conclusions: Survivors of childhood cancer experience significant age acceleration that is associated with an increased risk of mortality; longitudinal analyses are underway to validate these findings. Given the ease of estimating a DAI, this may be a feasible method to quickly identify survivors for novel and tailored interventions that can improve health and prevent premature mortality.

10049 Background: Survivors of pediatric CNS tumors may be at elevated risk for accelerated cognitive decline as they age through adulthood relative to the general population, which may be an early risk factor for dementia. Methods: Longitudinal analysis of 512 CNS tumor survivors (52.3% female, mean [SD] 30.6 [7.1] years at T1) and 232 siblings (57.8% female, mean [SD] 34.2 [8.4] years at T1) from the CCSS was conducted using the Neurocognitive Questionnaire (NCQ) to assess task efficiency, emotional regulation, organization and memory at two timepoints separated by a mean of 11.6 [0.7] years. Impairment in each NCQ domain was defined as a score ≥ 90th percentile of the CCSS sibling distribution at each survey, with decline defined as moving from unimpaired at T1 to impaired at T2. Treatment exposures were abstracted from medical records. Chronic health conditions were self-reported at T1 and graded according to CTCAE v4.3. Relative risk of decline for group, treatment and chronic condition predictors was estimated using generalized linear models with robust variance estimates. Mediation analysis examined direct effects of treatments and mediating effects of chronic conditions. All models were adjusted for age, sex, and race. Results: At T1, survivors demonstrated higher frequency of impaired memory (24.5% vs. 6.5%, p < 0.001), emotional regulation (14.3 % vs. 5.6%, p < 0.001), task efficiency (43.3% vs. 13.8%, p < 0.001) and organization (17.7% vs. 10.8%, p = 0.015) than siblings. Among those unimpaired at T1, more survivors vs. siblings declined in memory (34.7% vs. 7.8; RR 4.2, 95% CI 2.6-6.9), emotional regulation (15.5% vs. 5.0%; RR 2.8, 95% CI 1.5-5.3), task efficiency (22.7% vs. 7.0%; RR 2.9, 95% CI 1.7-5.2), and organization (14.5% vs. 2.9%; RR 4.9, 95% CI 2.1-11.0) by T2. Decline in survivor memory was associated with exposure to craniospinal irradiation (RR 1.9, 95% CI 1.3-2.8) and focal irradiation (RR 1.6, 95% CI 1.1-2.3) compared with no radiation, and exposure to Ara-C (RR 1.7, 95% CI 1.0-2.8) and cyclophosphamide (RR 1.7, 95% CI 1.01-2.8). Independent of therapy, serious/disabling or life-threatening cardiopulmonary conditions at T1 predicted future decline in memory (RR 1.5, 95% CI 1.02-2.2) and organization (RR 2.0, 95% CI 1.1-3.6), with the presence of 2 or more cardiopulmonary conditions associated with even higher risk (memory RR 2.6, 95% CI 2.0-3.1; organization RR 3.4, 95% CI 1.1-10.5). Chronic conditions did not mediate associations between treatment exposures and cognitive decline. Conclusions: CNS tumor survivors are at elevated risk for impairment and accelerated cognitive decline compared to siblings. Cranial radiation, Ara-C, cyclophosphamide, and cardiopulmonary morbidity are risk factors for decline. Survivors with these exposures/conditions may benefit from interventions to prevent additional future cognitive decline.

12013 Background: Childhood cancer therapy increases risk for cognitive impairment and other chronic conditions, which also may impact cognition. We assessed the unique impact of metabolic syndrome (MetS) on cognition in survivors participating in the St. Jude Lifetime Cohort Study. Methods: Participants included 4058 survivors of childhood cancer (53.9% female; mean [SD] age 30.1 [10.5] years at evaluation; 22.6 [10.1] years from diagnosis) who completed clinical evaluation and cognitive testing. MetS criteria followed Adult Treatment Panel III guidelines (at least 3 of: hypertension, high triglycerides, abdominal obesity, low high-density lipoprotein [HDL], high fasting glucose). Multivariable log-binomial regression models assessed risk of cognitive impairment associated with MetS stratified by survivors who did (n = 2301) or did not (n = 1757) receive central nervous system (CNS)-directed therapy. Mediation analysis assessed effects of MetS and physical activity in cranial radiotherapy (CRT)-associated cognitive impairment. Models were adjusted for age, sex, follow-up time and treatment exposures. Results: MetS was associated with increased risk of impaired attention (relative risk [RR] 1.34 95% confidence interval [CI] 1.07-1.66), processing speed (RR 1.25 CI 1.11-1.41) and executive function (RR 1.18 CI 1.01-1.37) in survivors with CNS-directed therapy and academic achievement (RR 1.84 CI 1.18-2.89), attention (RR 1.43 CI 1.10-1.87), and processing speed (RR 1.46 CI 1.21-1.75) in those without CNS-directed therapy. MetS components associated with cognitive impairment included abdominal obesity (memory RR 1.34 CI 1.13-1.59; processing speed RR 1.41 CI 1.24-1.59; executive function RR 1.21 CI 1.05-1.39) and low HDL (intelligence RR 1.26 CI 1.06-1.49; attention RR 1.27 CI 1.03-1.57; processing speed RR 1.17 CI 1.01-1.35; executive function RR 1.20 CI 1.05-1.37) in survivors with CNS-directed therapy. In survivors treated without CNS-directed therapy hypertension (academic achievement RR 1.49 CI 1.18-1.88; intelligence RR 1.34 CI 1.02-1.76; attention RR 1.42 CI 1.12-1.79; memory RR 1.45 CI 1.14-1.84; processing speed RR 1.30 CI 1.08-1.55; executive function RR 1.32 CI 1.08-1.62) and abdominal obesity (academic achievement RR 1.71 CI 1.07-2.72; processing speed RR 1.23 CI 1.02-1.49; executive function RR 1.38 CI 1.09-1.75) were associated with impairment. In mediation analyses, direct effects of CRT were identified, as were indirect effects through physical activity (processing speed β = 0.035 p < 0.01; attention β = 0.03 p < 0.01; executive function β = 0.172 p < 0.01). Conclusions: MetS increases risk of cognitive impairment in survivors, particularly abdominal obesity, hypertension and low HDL. Physical activity appears to partially mediate impact of CRT on cognitive outcomes and is an important target for interventions to lower impairment risk.

Venetoclax (VEN) is approved for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) as monotherapy (VENmono) or in combination with rituximab. Whether VEN plus anti-CD20 (VENcombo) is superior to VENmono is unknown. We conducted a multicenter, retrospective cohort analysis comparing 321 CLL patients treated with VENmono vs VENcombo across the United States and the United Kingdom. We examined demographics, baseline characteristics, dosing, adverse events, response rates, and outcomes. The primary endpoints were progression-free survival (PFS) and overall survival (OS), estimated by Kaplan-Meier method, in patients treated with VENmono vs VENcombo. Univariate and bivariate analyses were performed with COX regression. Three hundred twenty-one CLL patients were included (3 median prior treatments, 78% prior ibrutinib). The overall response rates (ORRs) were similar (VENmono, 81% ORR, 34% complete remission [CR] vs VENcombo, 84% ORR, 32% CR). With a median follow-up of 13.4 months, no differences in PFS and OS were observed between the groups. In unadjusted analyses, the hazard ratios (HRs) for PFS and OS for VENmono vs VENcombo were HR 1.0 (95% confidence interval [CI], 0.6-1.8; P = .7) and HR 1.2 (95% CI, 0.6-2.3; P = .5), respectively. When adjusting for differences between the cohorts, the addition of an anti-CD20 antibody in combination with VEN did not impact PFS (HR, 1.0; 95% CI, 0.5-2.0; P = .9) or OS (HR, 1.1; 95% CI, 0.4-2.6; P = .8). We demonstrate comparable efficacy between VENmono and VENcombo in a heavily pretreated, high-risk, retrospective cohort, in terms of both response data and survival outcomes. Prospective studies are needed to validate these findings.

Cancer-related cognitive impairment (CRCI) is an important clinical problem for cancer patients and survivors. In this review, we summarize studies investigating the occurrence of impaired cognition in patients with haematological malignancies. Most published studies focus on survivors of childhood acute lymphoblastic leukaemia and primary central nervous system lymphoma. We also discuss studies conducted in acute myeloid leukaemia, myelodysplastic syndromes, chronic myeloid leukaemia, Hodgkin lymphoma (HL), non-HL and chronic lymphocytic leukaemia. Although research in this area is still emerging, it appears that a subset of chemotherapy-treated haematological malignancy survivors experience CRCI. Future research should focus on expanding the literature reviewed here with larger studies appropriately powered to assess cognition via objective and subjective measures in a longitudinal fashion to tease apart the impact of disease and the various forms of cancer treatment.

10555 Background: Among young adult childhood cancer survivors, 8% meet the criteria for frailty, an aging phenotype associated with poor health. Frailty is associated with neurocognitive decline in the elderly general population, but this association has not been examined in young adult survivors of childhood cancer. Methods: Childhood cancer survivors (N = 845, mean [SD] age 30 [7] years, 22 [7] years post diagnosis, 52% male) were clinically evaluated for prefrailty/frailty (defined as ≥2/≥3 of muscle wasting, muscle weakness, low energy expenditure, slow walking speed, exhaustion) and completed neuropsychological assessments at baseline and five years later. Linear regression models estimated mean differences in neurocognitive decline in prefrail/frail survivors vs. non-frail survivors adjusting for age, sex, race, CNS therapy (cranial radiation, intrathecal chemotherapy, neurosurgery), and baseline neurocognitive performance. P-values were adjusted for multiple comparisons using false discovery rate (FDR). Results: 18% and 6% of survivors were prefrail and frail at baseline. Baseline frailty was associated with declines in visual-motor processing speed, short-term memory, and sustained attention (Table). Prefrailty and frailty were associated with declines in focused attention and executive function (Table). No significant associations were observed between prefrailty or frailty and decline in global cognition, academics, motor processing speed, long-term memory, verbal learning, or verbal fluency despite significant baseline cross-sectional associations. Conclusions: Young adult prefrail and frail survivors had greater declines in attention and executive function compared to non-frail survivors, domains commonly associated with aging. These findings suggest that interventions designed to mitigate components of frailty may also mitigate or prevent neurocognitive decline. [Table: see text]

Background: Long-term survivors of Hodgkin lymphoma (HL) experience neurocognitive impairment despite receiving no CNS-directed therapy, though little is known about the biologic mechanisms underlying this impairment. This study aimed to examine associations between pro-inflammatory and oxidative stress biomarkers with neurocognitive impairment in long-term HL survivors. Methods: 197 HL survivors (mean[SD] current age 36[8] years, 22[8] years post-diagnosis) and 199 age-, sex- and race/ethnicity-frequency-matched community controls completed neurocognitive testing (intelligence, attention, processing speed, memory) and systemic biomarker assessment. Neurocognitive scores were converted into age-adjusted Z-scores (μ=0, σ=1.0) using national normative data. Pro-inflammatory cytokines (IL-6, TNF-α) and markers of oxidative stress (malondialdehyde [MDA], oxidized low density lipoprotein, glutathione peroxidase [GPx]) were measured using multiplex assays on a Luminex platform. Biomarkers with undetectable concentrations were set at the lower limits of detection. Tertiles of each biomarker were created based on distributions in controls. Generalized linear models (GLM) compared survivors and controls on neurocognitive Z-scores adjusting for sex and on biomarker concentrations adjusting for sex and age. Sex-adjusted GLM compared the neurocognitive Z-scores across tertiles of each biomarker separately in HL survivors and controls. The analysis was limited to neurocognitive tests where survivors performed worse than controls after adjustment for the false discovery rate. Results: HL survivors demonstrated worse verbal reasoning (mean Z-score -0.3 vs. 0.1, p HL survivors, when compared to controls, demonstrated higher concentrations of TNF-α (β=0.9 95%CI 0.2, 1.6, p=0.012), IL-6 (β=0.8 95%CI 0.2, 1.5, p=0.013), oxidized low density lipoprotein (β=22.1 95%CI 14.1, 30.0, p Mean difference in neurocognitive tests scores across tertiles of MDA and GPx are presented in Table 1. Among HL survivors, higher concentrations of MDA were associated with worse verbal reasoning (β =-0.5 95%CI -0.9, -0.1), visual processing speed (β =-0.4 95%CI -0.8, -0.1), verbal learning (β =-0.4, 95%CI -0.8, -0.02), and short- (β =-0.5 95%CI -0.9, -0.1) and long-term memory (β =-0.5 95%CI -0.9, -0.04). Higher concentrations of GPx were associated with better verbal reasoning (β =0.51 95%CI 0.05, 0.97), visual processing speed (β =0.45 95%CI 0.02, 0.88) and focused attention (β =0.32 95%CI 0.01, 0.64) in HL survivors. No associations between neurocognitive function and MDA or GPx were found among community controls, suggesting HL survivors may be particularly susceptible to oxidative stress. No statistically significant associations with oxidized LDL were noted among survivors or controls. Among HL survivors, higher concentrations of IL-6 were associated with worse sustained attention (β=-1.1 95%CI -2.2, -0.02), and visuomotor (β=-0.4 95%CI -0.7, -0.01) and visual processing speed (β=-0.4 95% CI -0.7, -0.01). Among controls, these associations were less pronounced (β =-0.39 95%CI -0.69, -0.10, β =-0.41 95%CI -0.74, -0.09, and β =-0.10 95%CI -0.45, 0.24 respectively). Higher concentrations of IL-6 were associated with worse verbal learning and long-term memory in controls but not in HL survivors, suggesting the mechanisms by which IL-6 is associated with cognitive impairment may differ in survivors. Higher concentrations of TNF-α were associated with better long-term memory in survivors (β=0.6 95% CI 0.1, 1.0) but not controls. Conclusion: HL survivors have persistent neurocognitive impairment, inflammation, and oxidative stress up to 20 years after treatment. Associations between oxidative stress and intelligence, processing speed and memory deficits were unique to HL survivors, identifying potential causal pathways that warrant further research to understand the pathophysiology of neurocognitive impairment in HL. Disclosures No relevant conflicts of interest to declare.

Melanoma is significantly more common and is associated with a poorer prognosis in patients with an underlying B-cell malignancy. This study reports on the management of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) and a subsequent diagnosis of melanoma. In the Wilmot Cancer Institute CLL cohort, which includes 470 patients followed for 2849 person-years, 18 patients (3.8%) developed 22 melanomas. Fourteen melanomas were invasive, a significantly higher rate as compared with the age and sex matched general population (standardized incidence ratio [SIR] 6.32 (95% CI 3.45; 10.60). Melanomas were most often detected (n = 15; 68.2%) through active surveillance in a dermatology clinic. Most melanomas (n = 17; 77.3%) were detected at a non-advanced stage (pathological stage grouping III). The most common management was wide local excision without sentinel lymph node biopsy (n = 13, 59.1%). Management for the 4 (18.2%) patients with metastatic disease included the immune checkpoint inhibitor (ICI) pembrolizumab (n = 1), systemic chemotherapy with dacarbazine (n = 1), and palliative care (n = 2). The patient treated with ICI is in sustained remission of her melanoma after 23 cycles of therapy while her TP53 disrupted CLL continues to respond to ibrutinib therapy. We conclude that patients with CLL may benefit from active surveillance for melanoma leading to early excision of locally-manageable disease. In patients with metastatic melanoma, combined treatment with targeted kinase inhibitors and ICIs can be successful and tolerable. Larger prospective studies should be considered to further evaluate these approaches.

Purpose In this multicenter study, we evaluated the cumulative burden of morbidity (CBM) among > 1,200 testicular cancer survivors and applied factor analysis to determine the co-occurrence of adverse health outcomes (AHOs). Patients and Methods Participants were ≤ 55 years of age at diagnosis, finished first-line chemotherapy ≥ 1 year previously, completed a comprehensive questionnaire, and underwent physical examination. Treatment data were abstracted from medical records. A CBM score encompassed the number and severity of AHOs, with ordinal logistic regression used to assess associations with exposures. Nonlinear factor analysis and the nonparametric dimensionality evaluation to enumerate contributing traits procedure determined which AHOs co-occurred. Results Among 1,214 participants, approximately 20% had a high (15%) or very high/severe (4.1%) CBM score, whereas approximately 80% scored medium (30%) or low/very low (47%). Increased risks of higher scores were associated with four cycles of either ifosfamide, etoposide, and cisplatin (odds ratio [OR], 1.96; 95% CI, 1.04 to 3.71) or bleomycin, etoposide, and cisplatin (OR, 1.44; 95% CI, 1.04 to 1.98), older attained age (OR, 1.18; 95% CI, 1.10 to 1.26), current disability leave (OR, 3.53; 95% CI, 1.57 to 7.95), less than a college education (OR, 1.44; 95% CI, 1.11 to 1.87), and current or former smoking (OR, 1.28; 95% CI, 1.02 to 1.63). CBM score did not differ after either chemotherapy regimen ( P = .36). Asian race (OR, 0.41; 95% CI, 0.23 to 0.72) and vigorous exercise (OR, 0.68; 95% CI, 0.52 to 0.89) were protective. Variable clustering analyses identified six significant AHO clusters (χ2 P < .001): hearing loss/damage, tinnitus (OR, 16.3); hyperlipidemia, hypertension, diabetes (OR, 9.8); neuropathy, pain, Raynaud phenomenon (OR, 5.5); cardiovascular and related conditions (OR, 5.0); thyroid disease, erectile dysfunction (OR, 4.2); and depression/anxiety, hypogonadism (OR, 2.8). Conclusion Factors associated with higher CBM may identify testicular cancer survivors in need of closer monitoring. If confirmed, identified AHO clusters could guide the development of survivorship care strategies.

Testicular cancer survivors are at increased risk of cardiovascular disease after cisplatin-based chemotherapy. Among 787 testicular cancer survivors, the Framingham Risk Score for cardiovascular disease was elevated among less educated and less vigorously active patients, but did not differ by chemotherapy regimen (4 cycles of EP [etoposide and cisplatin] or 3–4 cycles of BEP [bleomycin, etoposide, and cisplatin]). Follow-up and counseling in high-risk subgroups is recommended. BACKGROUND: Testicular cancer survivors (TCSs) are at increased risk of cardiovascular disease (CVD) after cisplatin-based chemotherapy (CBCT). Identifying at-risk survivors would allow early intervention, but risk prediction tools such as the Framingham Risk Score (FRS) have not been applied to TCSs given modern chemotherapy. METHODS: TCSs > 1 year post-CBCT were evaluated. Associations between FRS and clinical, socioeconomic, and lifestyle measures and treatment regimen (4 cycles, etoposide and cisplatin [EP × 4]); 3 or 4 cycles, bleomycin plus EP (BEP × 3, BEP × 4) were analyzed with general linear multivariable models. Controls from the National Health and Nutrition Examination Survey were matched 1:1 to TCSs by age, race, and education with differences in mean FRS evaluated with 2-sided t tests. RESULTS: Of 787 TCSs (median age, 37.3 years; median follow-up, 4.2 years), 284, 342, and 161 received EP × 4, BEP × 3, or BEP × 4, respectively. TCSs had higher median systolic blood pressure (126 vs. 119 mm Hg; P < .001), but fewer were smokers (8.4% vs. 28.2%; P < .001) than controls. In multivariable analysis, no significant differences in FRS between EP × 4, BEP × 3, and BEP × 4 were observed, but less than college education (P < .001) and lack of vigorous exercise (P = .006) were associated with higher FRS. Mean FRS did not differ between TCSs and controls (6.8% vs. 7.3%; P = .67). CONCLUSION: This is the first study to apply the office-based FRS to TCSs. Chemotherapy regimen (BEP × 3 vs. EP × 4) was not associated with FRS, but less educated and less vigorously active patients had higher FRS, and present a high-risk subgroup for intense follow-up and counseling.

Second malignant neoplasms, cardiovascular disease, neurotoxicity and ototoxicity, pulmonary complications, hypogonadism, and nephrotoxicity are potentially life-threatening long-term complications of testicular cancer and its therapy. This article describes the pathogenesis, risks, and management of these late effects experienced by long-term testicular cancer survivors, who are defined as individuals who are disease free 5 years or more after primary treatment. Testicular cancer survivors should follow applicable national guidelines for cancer screening and management of cardiovascular disease risk factors. In addition, health care providers should capitalize on the time of cancer diagnosis as a teachable moment to introduce and promote lifestyle changes.

Lignans, a class of phytoestrogen commonly found in the Western diet, have been linked to decreased breast cancer risks in epidemiologic studies. Similar to estrogen receptors, the androgen receptor (AR), a prognostic factor in breast tumors, may be affected by lignans. However, few studies have investigated this link in the context of breast cancer etiology. We evaluated the relationship between dietary lignan intake and AR expression in incident breast tumors.Tumor tissue, epidemiological, and clinical data were collected from 216 women with incident, primary, histologically confirmed breast cancer enrolled in the Roswell Park Cancer Institute (RPCI) Data Bank and BioRepository (DBBR). On average, three tumor cores from each participant were assembled into a tissue micro array. After immunohistochemical staining, a trained RPCI pathologist determined AR status of each core. Lignan intake was calculated from a food frequency questionnaire collected upon enrollment into the DBBR.We observed a weak positive association between dietary lignans and AR expression [β (SE) 27.6 (17.0), p 0.10], and there was no significant difference in lignan intake across categories of AR expression (p = 0.09, R (2) = 0.35).Our results do not support a clear relationship between dietary lignan intake and AR expression. This investigation is the first, to our knowledge, to examine dietary lignan intake and AR expression in breast tumors. Further research is needed within a larger, more representative sample to determine whether lignan intake is truly associated with AR expression.

The objective of this study is to characterize the association between metabolic syndrome (MetS) and periodontitis in women, for which there is limited evidence.Cross-sectional associations between MetS and periodontitis were examined in 657 postmenopausal women aged 50 to 79 years enrolled in a periodontal disease study ancillary to the Women's Health Initiative Observational Study. Whole-mouth measures of alveolar crest height (ACH), clinical attachment level (CAL), probing depth (PD), gingival bleeding, and supragingival plaque and measures to define MetS using National Cholesterol Education Program criteria were from a clinical examination. Study outcomes were defined as: 1) mean ACH ≥3 mm, two sites ≥5 mm, or tooth loss to periodontitis; 2) ≥2 sites with CAL ≥6 mm and ≥1 site with PD ≥5 mm; 3) gingival bleeding at ≥50% of sites; and 4) supragingival plaque at ≥50% of sites. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).In unadjusted analyses, MetS (prevalence: 25.6%) was significantly associated with supragingival plaque (OR = 1.74; 95% CI: 1.22 to 2.50) and non-significantly associated with periodontitis defined by ACH (OR = 1.23; 95% CI: 0.81 to 1.85) and gingival bleeding (OR = 1.20; 95% CI: 0.81 to 1.77). Adjustment for age, smoking, and other confounders attenuated observed associations, though supragingival plaque remained significant (OR = 1.47; 95% CI: 1.00 to 2.16; P = 0.049). MetS was not associated with periodontitis defined by CAL and PD.A consistent association between MetS and measures of periodontitis was not seen in this cohort of postmenopausal women. An association between MetS and supragingival plaque requires further investigation.

We studied the risk of infections in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL). Major infections were defined as requiring hospital admission or intravenous antimicrobial treatment. Incidence rate (IR) ratios (IRR) were used to compare infection rates. Of 263 CLL patients followed for 936.9 person-years, 60% required treatment for progressive CLL (66 received ibrutinib). Infections occurred in 71.9% patients (IR 92.4/100 person-years) with 31.9% having major infections (IR 20.3/100 person-years) and infections causing 37.5% of deaths. CLL treatment was associated with significantly higher risk of major (IRR 3.31, 95% CI 2.10, 5.21) and minor (IRR 1.78, 95% CI 1.43, 2.22) infections. Compared to their previous chemoimmunotherapy patients receiving salvage ibrutinib therapy (n = 47) had a significantly increased risk of a major infection (IRR 2.35 95% CI 1.27, 4.34). The risk of infection in CLL patients remains high even with use of less immunosuppressive therapies.

Background: Testicular cancer survivors (TCS) are at significantly increased risk for cardiovascular disease (CVD), with metabolic syndrome (MetS) an established risk factor. No study has addressed clinical and genetic MetS risk factors in North American TCS. Patients and Methods: TCS were aged

Purpose To provide new information on adverse health outcomes (AHOs) in testicular cancer survivors (TCSs) after four cycles of etoposide and cisplatin (EPX4) or three or four cycles of bleomycin, etoposide, cisplatin (BEPX3/BEPX4). Methods Nine hundred fifty-two TCSs > 1 year postchemotherapy underwent physical examination and completed a questionnaire. Multinomial logistic regression estimated AHOs odds ratios (ORs) in relation to age, cumulative cisplatin and/or bleomycin dose, time since chemotherapy, sociodemographic factors, and health behaviors. Results Median age at evaluation was 37 years; median time since chemotherapy was 4.3 years. Chemotherapy consisted largely of BEPX3 (38.2%), EPX4 (30.9%), and BEPX4 (17.9%). None, one to two, three to four, or five or more AHOs were reported by 20.4%, 42.0%, 25.1%, and 12.5% of TCSs, respectively. Median number after EPX4 or BEPX3 was two (range, zero to nine and zero to 11, respectively; P > .05) and two (range, zero to 10) after BEPX4. When comparing individual AHOs for EPX4 versus BEPX3, Raynaud phenomenon (11.6% v 21.4%; P < .01), peripheral neuropathy (29.2% v 21.4%; P = .02), and obesity (25.5% v 33.0%; P = .04) differed. Larger cumulative bleomycin doses (OR, 1.44 per 90,000 IU) were significantly associated with five or more AHOs. Increasing age was a significant risk factor for one to two, three to four, or five or more AHOs versus zero AHOs (OR, 1.22, 1.50, and 1.87 per 5 years, respectively; P < .01); vigorous physical activity was protective (OR, 0.62, 0.51, and 0.41, respectively; P < .05). Significant risk factors for three to four and five or more AHOs included current (OR, 3.05 and 3.73) or former (OR, 1.61 and 1.76) smoking ( P < .05). Self-reported health was excellent/very good in 59.9% of TCSs but decreased as AHOs increased ( P < .001). Conclusion Numbers of AHOs after EPX4 or BEPX3 appear similar, with median follow-up of 4.3 years. A healthy lifestyle was associated with reduced number of AHOs.

11584 Background: Cancer-related cognitive impairment (CRCI) is an important clinical problem that may occur through pro-inflammatory pathways, cancer-related pathology, or cancer treatment. However, their relative contribution to CRCI is unknown. We used CLL, an indolent cancer of the immune system, as a novel model to study differential roles of disease, treatment, and inflammation in CRCI. Methods: We assessed cognitive function and serum pro-inflammatory marker levels in 150 CLL patients (100 treatment naïve and 50 chemotherapy treated) including 84 patients with high risk of CLL progression (deletion 17p, deletion 11q, unmutated IGHV, Zap70+, or CD38+). Objective neuropsychological tests assessed global cognition, processing speed, attention, memory, and executive function (NIH Toolbox Cognition, Hopkins Verbal Learning Test Revised (HVLT), Trail Making Test (TMTA/B)). Linear regression models examined cognitive outcomes in relation to risk, treatment, and pro-inflammatory markers while adjusting for sociodemographic covariates. Results: High risk patients recalled almost 2 fewer words on a memory task (HVLT immediate recall β = -1.8, 95%CI -3.3, -0.3) and took 15 seconds longer on an executive function task (TMTB β = 15.4, 95%CI 3.1, 27.6) than low risk patients, independent of treatment status. Treated patients reported significantly greater cognitive difficulties than treatment naive patients (FACT-Cog β = -5.2, 95%CI -8.7, -1.6) but did not perform worse on objective cognitive measures. Higher CRP was significantly associated with more self-reported cognitive difficulties, but higher levels of interleukin-6 and interferon-γ were significantly associated with better performance on objective measures of global cognition, attention, and executive function. Conclusions: High risk patients experienced impairments in executive function and memory suggesting that disease biology contributes to CRCI independent of treatment. Increasing levels of pro-inflammatory cytokines were associated with better cognitive performance indicating that the role of inflammation with respect to CRCI in CLL may be complex, possibly due to tumor-related immune deficiencies.

Introduction: Venetoclax (Ven), an oral BCL2 inhibitor, is approved for the treatment (tx) of relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Ven is generally well tolerated, and side effects observed in clinical trials have been consistent with other CLL tx. Clinical trials using the approved dose escalation schedule report negligible rates of clinical tumor lysis syndrome (TLS). We aimed to understand rates of select adverse events (AEs) including cytopenias, infections, and TLS in CLL patients (pts) treated with Ven in community and academic settings. To do so, we examined 297 pts with CLL who received Ven, either alone or paired, in this multicenter, international study. Methods: We conducted a retrospective cohort study of Ven treated pts with CLL across at 15 academic (n=169) and 51 community (n=128) centers outside of the clinical trial setting. This study represents a collaboration between US centers, CLL Collaborative Study of Real World Evidence (CORE), and UK CLL Forum. Demographics, baseline disease characteristics, Ven dosing, TLS risk (per FDA Ven label) and prophylaxis, and AEs were collected. Lab vs. clinical TLS was defined by Howard criteria. PFS was estimated by Kaplan Meier methodology. All comparisons were descriptive. Results: Of the 297 pts examined, median age at Ven initiation was 67 (range 37-91). The group was 69% male, 96% had R/R CLL, and 45% had del17p. Baseline characteristics stratified by practice setting are included in Table 1. 80% received Ven as monotherapy while 20% received it paired with another agent (anti-CD20 mAb (75%), ibrutinib (8.5%), other (16.5%)). All pts were treated outside of clinical trials. During dose escalation, 81% achieved a 400 mg dose and 65% maintained 400 mg following escalation (cyp3A4 use unknown). TLS risk was low in 40%, intermediate (int) in 32%, and high risk in 28%. CT scan prior to Ven initiation was performed in 62%. At least one hospitalization occurred for 56% of low, 80% of int, and 88% of high risk pts (63% of the total cohort). Table 1 describes the distribution of TLS risk and frequency of hospitalizations in academic, community centers. TLS prophylactic measures were available for a subset of pts. Allopurinol was used for 91% (n=68/75) of low, 93% (n=52/56) of int, and 94% (n=29/31) of pts at high risk for TLS. Rasburicase was used for 27% (n=28/102) of low, 42% (n=34/81) of int, and 72% (n=57/79) of high risk pts. Normal saline was used in 85% (n=62/73) of low, 88% (n=49/56) of int, and 97% (n=30/31) of high risk pts. TLS occurred in 8.4% of pts (n=25/297). Three lab and 2 clinical events occurred in low risk pts, 7 lab and 3 clinical events in int risk pts, and 7 lab and 3 clinical events in high risk pts. Of pts with TLS, 1 has discontinued Ven. Of pts with clinical TLS, all were hospitalized, received allopurinol and normal saline, and 28% received rasburicase. 72% with TLS had creatinine clearance Select AEs were neutropenia (ANC7 stools/day) 6.9%. For the subset who received Ven paired, AEs were not increased: 35% neutropenia, 29% thrombocytopenia, 22% infection, 6.3% neutropenic fever, and 6.4% diarrhea. TLS was observed in 3.4% of pts who received Ven paired vs. 9.3% who received Ven monotherapy. 29% pts required ≥1 dose reduction and 32% had ≥1 dose interruption. Median length of dose interruption was 7 days (range 1 - 132). 22 pts (7.4%) discontinued Ven due to an AE. PFS was similar in pts with ≥1 dose interruption vs. 0, pts who required dose interruption ≥8 days vs. Conclusions: Ven was well tolerated in this cohort; AE rates were similar to those reported in clinical trials. Both academic and community sites employed TLS prophylaxis consistent with FDA/EMA recommendations resulting in a small proportion of clinical TLS events ( Disclosures Fox: Sunesis: Consultancy; Celgene: Consultancy, Other: Travel support, Speakers Bureau; Roche: Consultancy, Other: Travel support, Research Funding, Speakers Bureau; Gilead: Consultancy, Other: Travel support, Research Funding, Speakers Bureau; AbbVie: Consultancy, Other: Travel support, Research Funding, Speakers Bureau; Janssen: Consultancy, Other: Personal fees and non-financial support, Speakers Bureau. Eyre:Gilead: Consultancy, Other: travel support; Abbvie: Consultancy, Other: travel support; Roche: Consultancy; Janssen: Consultancy, Other: travel support; Celgene: Other: travel support. Allan:Verastem: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Acerta: Consultancy; Genentech: Membership on an entity's Board of Directors or advisory committees; Sunesis: Membership on an entity's Board of Directors or advisory committees. Schuster:OncLive: Honoraria; Physician's Education Source, LLC: Honoraria; Dava Oncology: Consultancy, Honoraria; Genentech: Honoraria, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis Pharmaceuticals Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Nordic Nanovector: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Nabhan:Cardinal Health: Employment, Equity Ownership. Hill:Amgen: Research Funding; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Shah:Lentigen Technology: Research Funding; Miltenyi: Other: Travel funding, Research Funding; Juno Pharmaceuticals: Honoraria; Exelexis: Equity Ownership; Oncosec: Equity Ownership; Geron: Equity Ownership. Lamanna:Jannsen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Verastem: Research Funding; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Acerta: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees. Cheson:AbbVie, Roche/Genentech, Pharmacyclics, Acerta, TG Therapeutics: Consultancy. Coombs:AROG: Other: Travel fees; H3 Biomedicine: Honoraria; Abbvie: Consultancy; DAVA Oncology: Honoraria; Incyte: Other: Travel fees. Barr:AbbVie, Gilead: Consultancy. Skarbnik:Gilead Sciences: Honoraria, Speakers Bureau; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Honoraria, Speakers Bureau; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Jazz Pharmaceuticals: Honoraria, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Shadman:Pharmacyclics: Research Funding; Acerta Pharma: Research Funding; AstraZeneca: Consultancy; Genentech: Consultancy; Celgene: Research Funding; Verastem: Consultancy; Gilead Sciences: Research Funding; TG Therapeutics: Research Funding; AbbVie: Consultancy; Genentech: Research Funding; Mustang Biopharma: Research Funding; Beigene: Research Funding; Qilu Puget Sound Biotherapeutics: Consultancy. Ujjani:AbbVie: Consultancy, Speakers Bureau. Pagel:Pharmacyclics, an AbbVie Company: Consultancy; Gilead: Consultancy. Jacobs:Genentech: Honoraria. Schuh:Giles, Roche, Janssen, AbbVie: Honoraria. Brander:Genentech: Consultancy, Honoraria, Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; Novartis: Consultancy, Other: DSMB; BeiGene: Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; DTRM: Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; TG Therapeutics: Consultancy, Honoraria, Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; Acerta: Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; AbbVie: Consultancy, Honoraria, Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; Pharmacyclics, an AbbVie Company: Consultancy, Honoraria, Research Funding; Teva: Consultancy, Honoraria. Mato:Pharmacyclics: Consultancy, Honoraria, Research Funding; TG Therapeutics: Research Funding; Regeneron: Research Funding; Sunesis: Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Acerta: Research Funding; Abbvie: Consultancy; AstraZeneca: Consultancy; Celgene: Consultancy; Prime Oncology: Speakers Bureau.

Introduction: Venetoclax (Ven) is approved for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) as monotherapy (Ven mono) or in combination (Ven paired) with rituximab based on clinical trials with selected patients (pts) and limited ibrutinib exposure. Whether Ven paired is superior to Ven mono, patterns of care, and outcomes following Ven discontinuation are unknown. Further, better delineation of adverse events (AEs) when Ven is used outside of clinical trials is needed. To address these gaps, we conducted a multicenter, international study in partnership with CLL Collaborative Study of Real World Evidence (CORE) and UK CLL Study Forum examining the clinical experience of 348 Ven treated CLL pts, representing the largest series of Ven treated pts reported to date. Methods: We conducted a retrospective cohort analysis of CLL pts treated with Ven across 24 US and 42 UK academic and community centers. We examined demographics, baseline disease characteristics, dosing, AEs, TLS risk and outcomes, response rates, outcomes (overall survival (OS) and progression free survival (PFS)), and tx sequencing. TLS events were defined by Howard criteria. PFS and OS were estimated by the Kaplan Meier method. Comparisons of outcomes used the Log Rank test. Univariate and multivariate analyses were performed with COX regression. All other comparisons were descriptive. Results: Of these 348 CLL pts, 94% were R/R, median age 67 years (range:37-91), 69% male, 85% white, and 73% Rai stage ≥2. 19% received Ven on clinical trial. 79% had Ven mono; Ven was paired most commonly with anti-CD20 (n=51) and ibrutinib (n=10). Pts received a median of 3 tx (range 0-15) before Ven; 78% received ibrutinib, 29% received PI3Ki, 20% had ≥2 prior kinase inhibitors, and 68% had chemoimmunotherapy. Median time from most recent tx to Ven start was 1.1 months (range 0-62). Pre-Ven prognostic markers included 43% del17p, 34% TP53 mutated, 24% del11q, 38% complex karyotype (≥ 3 abnormalities), and 84% IGHV unmutated (Table 1). TLS risk was low in 38%, intermediate in 34% and high in 28%. During ramp up, TLS was observed in 10% (22 lab, 9 clinical TLS events, 3 missing data). Following dose escalation, 70% achieved a stable Ven dose of 400 mg, 33% required ≥ 1 dose interruption and 27% required ≥ 1 dose reduction. AEs included grade 3 neutropenia 39%, grade 3 thrombocytopenia 29%, infections 25%, grade ≥ 2 diarrhea 7.8%, and neutropenic fever 7.7%. AEs were similar whether treated on or off clinical trial. The ORR to Ven mono, Ven paired was 81% (34% CR), 86% (29% CR). With a median follow-up of 14.2 months, median PFS and OS were not reached (12 month PFS 74%, OS 82%). Figure 1 depicts PFS stratified by Ven mono vs. paired, clinical trial vs. clinical practice, del17p status, and complex karyotype. Pts who discontinued Ven due to AEs had better OS compared with those who discontinued due to progression or Richter Transformation (RT) (Median OS 47 vs. 15.1 vs. 8.6 months, respectively). In multivariate analyses, complex karyotype was the only independent predictor of PFS (HR 2.8, p Conclusions: In this heavily pretreated, poor risk group, Ven showed favorable outcomes with comparable toxicity and efficacy on or off clinical trial. Similar outcomes were observed for Ven mono and Ven paired; longer follow up is needed from studies of Ven paired to understand depth and durability of response. Complex karyotype independently predicted inferior PFS and OS. Without complex karyotype, del(17p), multiple lines of prior tx, and prior ibrutinib tx were independent predictors of inferior outcomes. Outcomes of retreatment with KI in Ven-failure previously treated with KI were poor. Data on sequencing cellular therapies post Ven is forthcoming. Disclosures Mato: AbbVie: Consultancy, Research Funding; Pharmacyclics, an AbbVie Company: Consultancy, Research Funding; Regeneron: Research Funding; AstraZeneca: Consultancy; Medscape: Honoraria; TG Therapeutics: Consultancy, Research Funding; Acerta: Research Funding; Prime Oncology: Honoraria; Portola: Research Funding; Celgene: Consultancy; Johnson & Johnson: Consultancy. Eyre:Abbvie: Consultancy, Other: travel support; Janssen: Consultancy, Other: travel support; Roche: Consultancy; Gilead: Consultancy, Other: travel support; Celgene: Other: travel support. Nabhan:Cardinal Health: Employment, Equity Ownership. Lamanna:Acerta: Research Funding; TG Therapeutics: Research Funding; Jannsen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Verastem: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Hill:Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Research Funding; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Brander:Pharmacyclics, an AbbVie Company: Consultancy, Honoraria, Research Funding; Acerta: Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; Novartis: Consultancy, Other: DSMB; TG Therapeutics: Consultancy, Honoraria, Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; Teva: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; Genentech: Consultancy, Honoraria, Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; DTRM: Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; BeiGene: Other: Institutional research funding for non investigator initiated clinical trial, Research Funding. Barr:AbbVie, Gilead: Consultancy. Cheson:AbbVie, Roche/Genentech, Pharmacyclics, Acerta, TG Therapeutics: Consultancy. Shah:Geron: Equity Ownership; Lentigen Technology: Research Funding; Exelexis: Equity Ownership; Oncosec: Equity Ownership; Miltenyi: Other: Travel funding, Research Funding; Juno Pharmaceuticals: Honoraria. Allan:AbbVie: Membership on an entity's Board of Directors or advisory committees; Verastem: Membership on an entity's Board of Directors or advisory committees; Acerta: Consultancy; Sunesis: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees. Kennard:AbbVie, Gilead, Verastem: Consultancy. Schuster:Gilead: Membership on an entity's Board of Directors or advisory committees; Nordic Nanovector: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Honoraria, Research Funding; Physician's Education Source, LLC: Honoraria; Pfizer: Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria, Research Funding; Dava Oncology: Consultancy, Honoraria; OncLive: Honoraria; Novartis Pharmaceuticals Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Skarbnik:Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Jazz Pharmaceuticals: Honoraria, Speakers Bureau; Genentech: Honoraria, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead Sciences: Honoraria, Speakers Bureau. Coombs:AROG: Other: Travel fees; Abbvie: Consultancy; Incyte: Other: Travel fees; DAVA Oncology: Honoraria; H3 Biomedicine: Honoraria. Ujjani:AbbVie: Consultancy, Speakers Bureau. Jacobs:Genentech: Honoraria. Pagel:Pharmacyclics, an AbbVie Company: Consultancy; Gilead: Consultancy. Schuh:Giles, Roche, Janssen, AbbVie: Honoraria. Shadman:Celgene: Research Funding; Gilead Sciences: Research Funding; Mustang Biopharma: Research Funding; TG Therapeutics: Research Funding; AstraZeneca: Consultancy; Pharmacyclics: Research Funding; Genentech: Research Funding; Genentech: Consultancy; Acerta Pharma: Research Funding; Beigene: Research Funding; Verastem: Consultancy; Qilu Puget Sound Biotherapeutics: Consultancy; AbbVie: Consultancy. Fox:Abbvie: Consultancy, Other: travel support, Research Funding, Speakers Bureau; Janssen: Consultancy, Other: travel support, Speakers Bureau; Gilead: Consultancy, Other: travel support, Research Funding, Speakers Bureau; Roche: Consultancy, Other: travel support, Research Funding, Speakers Bureau; Celgene: Consultancy, Other: travel support, Speakers Bureau; Sunesis: Consultancy.

153 Background: CLL is an indolent lymphoma effecting aging populations. Early stage patients are assigned to active surveillance and only 10% of patients require treatment at diagnosis. Active surveillance for CLL may increase susceptibility to anxiety and depression, resulting in enhanced comorbidities and reduced quality of life. However, little is known about the prevalence and risk factors of anxiety and depression in CLL. Methods: 125 CLL patients that were treatment naïve (n = 86) or previously chemotherapy-treated (n = 39) completed anxiety and depression questionnaires (State Trait Anxiety Index (STAI) and Center for Epidemiologic Studies Depression (CES-D)). Multivariable linear regression was used to examine associations with STAI/CES-D score. Logistic regression was used to examine clinically meaningful anxiety and depression, using validated cut points of 40 for the STAI and 16 (or on antidepressants) for the CES-D. All models included treatment status (treatment naïve vs. treated), age, gender, ECOG grade, time since diagnosis, education, & disease stage. Results: Patients had a median age of 65, were mostly male (60.8%), Caucasian (96%), well educated (55% ≥ college), and had low stage CLL (66% stage 0) and good performance status (67% ECOG 0). 20 and 24% of patients had clinically meaningful anxiety or depression (11% had both). Treatment and time since diagnosis were not associated with anxiety or depression. Older age was associated with better STAI and CES-D scores (STAI β = -0.34 (95%CI -0.52, -0.17) CES-D β = -0.27 (95%CI -0.42, -0.12)), and each 1 year increase in age was associated with a 9% decrease in odds of anxiety and a 7% decrease in odds of depression (OR 0.91(95%CI 0.86, 0.96) OR 0.93 (95%CI 0.88, 0.98) respectively). An ECOG grade of 3 or 4 was a significant predictor of increased depression risk (OR 2.84 (95%CI 1.03, 7.82)) and worse CES-D scores (β = 4.69 (95%CI 8.09, 1.29)) but not of anxiety. Conclusions: Anxiety and depression are common among CLL patients. Poor performance status was associated with more depression while older age was associated with less anxiety and depression. Future studies should investigate potential interventions for anxiety and depression in younger CLL patients.

59 Background: A major challenge in providing quality survivorship care to cancer patients is efficiently and effectively identifying and scheduling patients who need a Survivorship Visit (SV). While the Commission on Cancer (CoC) Standard 3.3 defines which patients require a Survivorship Care Plan (SCP), staff need to operationalize the definition and search the clinic’s patient records on a regular basis to accurately identify eligible patients. This is a challenge for a busy cancer center. Methods: In July 2017 the Judy DiMarzo Cancer Survivorship Program instituted a full time Data Analyst (DA) to assist in identifying survivors using the OncoLog Cancer Registry and the Electronic Medical Record (EMR). Previously the identification process was limited to the EMR, and the Survivorship Program Nurse Coordinator (NC) was a combined role overseeing metrics, identifying patients and assisting with SVs. Currently the DA has piloted a method extracting data monthly from OncoLog and the EMR to assess eligibility of Standard 3.3. The data is compiled and sent to the NC who assists the cancer-specific service lines responsible for the patients identified to ensure SVs occur in a timely manner. Results: Our pilot intervention resulted in a 283% increase in SVs per month, from an average of 30 SVs to 115 SVs per month. The overall achievement for the CoC SV delivery requirement increased from 16% prior to the intervention to 33% in just 3 months. GI increased from 5% to 20%. Lung increased from 16% to 39%. The average SV was 3 months after the end of treatment. Approximately 60 hours was dedicated to establishing this method and 35 hours per month in the eligibility, identification process. Conclusions: By adding a DA role, extracting data from Oncolog and the EMR, as well as increasing accountability at the service line level to improve identification and scheduling of eligible patients, the delivery of SCPs to eligible patients substantially increased. Nevertheless this process is time consuming and will likely not be sufficient to ensure that all eligible survivors receive appropriate care. Consequently, additional, systematic improvements in this process should be explored such as EMR methodologies to automate patient identification.

10014 Background: Large nationwide studies are needed to assess CRCI. Methods: NCORPs recruited BC patients and age-matched non-cancer controls. Computerized ((CANTAB Delayed Match to Sample (DMS), Rapid Visual Processing (RVP), Verbal Recognition Memory (VRM)), paper-based ((Controlled Oral Word Association (COWA), and Trail Making Test (TMT)) , and phone-based (category fluency, word recall, backward counting and digits backward) cognitive assessments of memory, attention, and executive function at pre-chemotherapy, post-chemotherapy, and 6 months follow-up (or time-equivalent for controls) were completed. Longitudinal mixed model (LMM)s included group, time, time*group, and adjusted for age, education, reading, anxiety, and depression. Results: 580 BC patients (mean age = 54) and 363 controls (mean age = 53) were assessed. In all LMMs, there was a significant group*time interaction depicting lower scores in patients compared to controls (p < 0.005) except for TMT (p = 0.09). For longitudinal change on the DMS memory test (primary aim), we observed no significant difference between groups from pre- to post-chemotherapy but did observe a significant difference from pre-chemotherapy to follow-up (p = 0.017) where patients significantly declined (p = 0.005) and controls did not change. We observed similar results for RVP. For VRM, there was a significant pre- to post-chemotherapy group difference (p = 0.003). For COWA, patients significantly declined and controls significantly improved reflecting a significant between group difference (p < 0.001) from pre- to post-chemotherapy. For TMT, both groups significantly improved with patients improving less than controls reflected by a significant between group difference (p = 0.04) that remained a trend at follow-up (p = 0.06). On all phone tests, there was a significant between group effect from both pre- to post-chemotherapy and at follow-up with patients doing less well than controls (all p < 0.001). Conclusions: This nationwide study shows CRCI in BC patients persists in multiple cognitive domains up to 6 months post-chemotherapy compared to controls. Clinical trial information: NCT01382082.

10045 Background: Cancer related fatigue (CRF) is commonly reported among breast cancer survivors and can negatively impact quality of life and treatment adherence. Large, prospective, longitudinal studies assessing CRF in breast cancer survivors compared to matched non-cancer controls are rare. Methods: Breast cancer survivors (n = 581, stage I-IIIBC, mean age 53.4) from community oncology clinics and age-matched controls (n = 364, mean age 52.6) completed the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI, scores range -24 to 96) prior to chemotherapy (T1), at chemotherapy completion (T2) and six-months after chemotherapy (T3). Linear mixed models compared trajectories of CRF over time in survivors compared to controls, adjusting for age, education, race, BMI, marital status, menopausal status, and depressive symptoms. Results: Survivors reported greater CRF compared to controls at all time points (mean total score T1 9.4 vs. -3.7, T2 17.0 vs. -3.3, and T3 8.5 vs. -3.1, all p < 0.001; all subscales p < 0.001). From T1 to T2 survivors experienced a significant increase in CRF as shown in the total score (mean change (MC) = 8.3; effect size (ES) = 0.4 , p < 0.001), and general, mental, and physical sub-scales (MC = 4.3, 2.1, 3.2 , ES = 0.7, 0.5, 0.7, respectively, all p < 0.001), while controls experience minimal changes (MC = 0.1-0.3, ES < 0.09, p > 0.05). At T3 survivors total score returned to T1 values (MC = -0.1, ES = 0.01, p = 0.461), which was, however, still greater than controls ( p < 0.001), while general, mental, and physical CRF subscale scores remained significantly higher than T1 values (MC = 1.2, 1.7, 1.9, ES = 0.2, 0.4, 0.3, respectively, all p < 0.001; controls no change). Group by time interactions indicated changes over time were greater in the survivors than controls (p < 0.001). In multivariate analyses of survivors, age, BMI, performance status, and baseline depression significantly predicted change in CRF. Conclusions: These results from the largest well-controlled study to date showed that breast cancer survivors experience significantly more CRF prior to and after chemotherapy compared to healthy controls. Further research should aim to identify subgroups of survivors most susceptible to CRF.

10075 Background: TCS are an important group in which to characterize late effects of cancer and its therapy given their young age at diagnosis and high cure rate. We comprehensively evaluated CBM and identified associated clinical, sociodemographic, and behavioral risk factors among TCS given cisplatin based chemotherapy in a multicenter study. Methods: TCS completed a comprehensive health questionnaire. Responses were grouped into 22 adverse health outcomes (AHO) and graded by severity. A CBM score was calculated based on AHO number and severity, following Geenen et al (JAMA 2007). Multivariable ordinal logistic regression examined the association of clinical, sociodemographic, and behavioral factors with CBM. Variable-based hierarchical clustering identified individual AHOs that co-occurred. Results: Among 1,215 TCS (median age at evaluation 38 y, range 19-68 y; time since chemotherapy 4.6 y), over 20% had a CBM score of high (17%), very high (4%) or severe (0.4%). Most TCS, however, had CBM scores of low (37%), medium (28%), very low (9%) or none (5%). In a multivariable model controlling for time since chemotherapy, older attained age (OR 1.2; 95% CI 1.1 - 1.3), being widowed/divorced/separated (OR 1.8; 95% CI 1.1 - 3.1), having less than college-level education (OR 1.7; 95% CI 1.3 - 2.2), being retired/on disability (OR 2.5; 95% CI 1.2 - 5.3), and receipt of 4 cycles of BEP vs. 4 cycles of EP or 3 cycles of BEP (OR 1.3; 95% CI 1.01 - 1.8) were associated with increased odds of a worse CBM score; vigorous exercise (OR 0.7; 95% CI 0.5 - 0.9) and non-white race (OR 0.6; 95% CI 0.4 - 0.9) were associated with decreased odds. A separate cluster analysis revealed five groups of AHOs: those known to be cisplatin-related (e.g. neuropathy, ototoxicity); metabolic abnormalities (e.g. hypercholesterolemia, diabetes); vascular damage (e.g. stroke); testicular cancer-related (e.g. hypogonadism); and other (e.g. thyroid disease). Conclusions: TCS with factors associated with worse CBM may be candidates for closer monitoring. If confirmed, our cluster analysis showing that groups of conditions tend to co-occur in TCS could provide guidance for survivorship care plans.

102 Background: Testicular cancer has an excellent prognosis since the introduction of platinum-based CHEM. However, several European studies report an excess of cardiovascular disease (CVD) in TCS. MetS is a cluster of cardiovascular risk factors that doubles CVD risk, with several European series noting a prevalence ranging from 13-39% in TCS. In the first large multi-center North American study of TCS, we examine the prevalence of and potential risk factors for MetS after modern CHEM (NCI R01 CA157823). Methods: Eligible TCS were

37 Background: Quality cancer survivorship care has multiple missions 1) develop personalized disease-specific treatment summaries (TS) and evidence-based survivorship plans (SPs), 2) foster recognition amongst Primary Care Providers (PCPs) of the consequences of cancer and its therapy, 3) coordinate care amongst providers, 4) use technology to foster communication and mining data, 5) train residents/fellows, 6) determine knowledge gaps for research, 7) engage community health providers, 8) publicize and raise funds, and 9) develop metrics to assess outcomes. Here we describe initial steps toward these goals. Methods: The University of Rochester Judy DiMarzo Cancer Survivorship program is a multidisciplinary effort across 7 centers involving oncologists, PCPs, social workers, integrated oncology, legal/financial services, and survivors. Survivors are identified at two critical time points: after (1) completion of primary curative therapy = transition visit, (2) discontinuation of routine oncologic follow-up and transition of care to their PCP = shared care visit. These visits are staffed within each cancer discipline. Trainees (15-20/year) probe existing evidence and draft TS/SP templates that are vetted by that cancer discipline. Patient needs are surveyed; institutional and community resources are identified. Results: In 3 years, 1037 patients had survivorship visits - 859 transition visits, 178 shared care visits. Cancers include breast (31%), head & neck (17%), lymphoma (15%), GI (15%), GU (11%), GYN (7%), lung (3%), melanoma and sarcoma (1%) with continuing refinement of systematic patient identification. Visits by year were: 120 in 2013, 266 in 2014, and 470 in 2015. Amongst the 1037 patients, the 6 most common needs were exercise, emotional, return to work, nutrition, financial, and pain. Conclusions: Our program is systematically embracing challenges to deliver evidence-based, individualized TS/SPs for survivors, as well as train future oncology providers in survivorship care. Current areas of focus are better engaging PCPs, ensuring program sustainability, improving technology use to mine data, measuring outcomes, establishing rural outreach, and fostering survivorship research.

Introduction: Infection is a major source of morbidity and mortality in CLL. Improved treatment efficacy and decreased immune toxicity of treatment could have altered the spectrum and consequences of infections in patients with CLL. A better understanding of infections complicating the course of non-selected patients with CLL could be useful in improving medical management. Methods: Demographic and clinical information was retrospectively extracted from medical records for clinic visits between May 1st, 2000 and May 1st, 2016 for all patients enrolled in the Wilmot Cancer Institute (WCI) CLL database. Data collected on incident infections included site, etiology, treatment, and setting of care. Major infections were defined as requiring either an inpatient stay or IV antimicrobial treatment. Minor infections were defined as any infectious episode requiring oral antimicrobials and outpatient treatment. Incidence rate ratios (IRR) were generated using Poisson regression to compare infection rates across treatment categories. Results: Two hundred and seventy-five CLL patients contributed 937.7 person-years (p-yrs) of follow up from their first clinic visit at WCI (median follow up 2.1 yrs). Median age at diagnosis was 61.6 and only 8.2% of patients had advanced stage CLL. Most patients were CD38 negative (64.7%), ZAP70 negative (54.6%), and IGHV mutated (51.2%, n=89) and 75.1% had either 13q14 deletion as the only defect or no abnormality on FISH analysis. Sixty percent of patients needed treatment for progressive CLL; among those treated, 50.9% were ever treated with either a purine analog or alemtuzumab, 30.4% were treated with other chemotherapies, and 18.6% had non-chemotherapy treatment. B-cell receptor inhibitor (BCR) therapy was used in sixty-seven patients (63 ibrutinib, 4 idelalisib) and was the only therapy in 18 of them (BCR only). Thirty percent of patients experienced at least one major infection (incidence rate 20.4 per 100 p-yrs) and 62.9% experienced at least one minor infection (69.3 per 100 p-yrs). The most common sites of major infections were the lower respiratory tract (7.8 per 100 p-yrs), skin (2.6 per 100 p-yrs), and urogenital tract (2.0 per 100 p-yrs). Minor infections most commonly affected the upper respiratory tract (26.8 per 100 p-yrs), skin (11.0 per 100 p-yrs, including shingles: incidence rate of 2.8 per 100 p-yrs), and bronchi (9.3 per 100 p-yrs). Patients treated for CLL had a higher risk of major infections (IRR 4.15, 95%CI 2.53, 6.80) and minor infections (IRR 1.48, 95%CI 1.23, 1.79) compared to those never treated. The age and gender adjusted risk of both major and minor infections were significantly increased by treatment with a purine analog or alemtuzumab (Table 1). The risk of major infection in the BCR only group was significantly higher than treatment-naive patients (IRR 3.31 95%CI 1.13, 9.80) and was 43% lower compared to patients treated with other modalities (IRR 0.57, 95%CI 0.21,1.55). The BCR group had a significantly higher risk of a minor infection compared to untreated patients (IRR 1.86 95% 1.14, 3.04), but had a slightly lower risk compared to those treated with other modalities (IRR 0.93 95%CI 0.57, 1.48). The BCR only group had a longer infection free survival compared to those on BCR inhibitor salvage therapy (Figure 1). An intra-patient comparison of infection risk for patients receiving BCR inhibitor salvage therapy compared to their previous chemoimmunotherapy showed an 33% increase in the risk of a major infection (IRR 1.33 95%CI 0.96, 1.86) and a 185% increased risk of a minor infection (IRR 2.85 95%CI 1.57, 5.18). Conclusion: CLL is complicated by a large number of infections, especially in patients with progressive disease who require treatment. Minor infections contribute to considerable disease burden and can have serious sequelae (e.g. post herpetic neuralgia). Given their decreased immune toxicity profile, BCR inhibitors may decrease the risk of infections; however, this has not yet been confirmed. Our sample of CLL patients treated solely with BCR inhibitors experienced higher rates of infection compared to untreated patients. Additionally, patients treated with BCR inhibitors as salvage therapy still experienced higher rates of infection compared to their time on chemoimmunotherapy. Therefore, patients treated with BCR inhibitors should be carefully monitored for infections that can cause significant morbidity or mortality. Disclosures Barr: Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; AbbVie: Consultancy.

10087Background: TCS are at increased risk of CVD. Few clinical studies have comprehensively evaluated CVD risk factors through physical exams, lipid panels, and health behaviors in North American ...