Management of Oligometastatic and Locally Recurrent Urothelial Carcinoma.

PURPOSE OF REVIEW: To summarize and evaluate the literature on treatment approaches for oligometastatic and locally recurrent urothelial cancer. RECENT FINDINGS: There is no clear definition for oligometastatic urothelial cancers due to limited data. Studies focusing on oligometastatic and locally recurrent urothelial cancer have been primarily retrospective. Treatment options include local therapy with surgery or radiation, and generalized systemic therapy such as chemotherapy or immunotherapy. Oligometastatic and locally recurrent urothelial cancers remain challenging to manage, and treatment requires an interdisciplinary approach. Systemic therapy is nearly always a component of current care in the form of chemotherapy, but the role of immunotherapy has not been explored. Consideration of surgical and radiation options may improve outcomes, and no studies have compared directly between the two localized treatment options. The development of new prognostic and predictive biomarkers may also enhance the treatment landscape in the future.

Predictors of high-intensity care at the end of life among older adults with solid tumors: A population-based study.

INTRODUCTION: High-intensity end-of-life (EoL) care can be burdensome for patients, caregivers, and health systems and does not confer any meaningful clinical benefit. Yet, there are significant knowledge gaps regarding the predictors of high-intensity EoL care. In this study, we identify risk factors associated with high-intensity EoL care among older adults with the four most common malignancies, including breast, prostate, lung, and colorectal cancer. MATERIALS AND METHODS: Using SEER-Medicare data, we conducted a retrospective analysis of Medicare beneficiaries aged 65 and older who died of breast, prostate, lung, or colorectal cancer between 2011 and 2015. We used multivariable logistic regression to identify clinical, demographic, socioeconomic, and geographic predictors of high-intensity EoL care, which we defined as death in an acute care hospital, receipt of any oral or parenteral chemotherapy within 14 days of death, one or more admissions to the intensive care unit within 30 days of death, two or more emergency department visits within 30 days of death, or two or more inpatient admissions within 30 days of death. RESULTS: Among 59,355 decedents, factors associated with increased likelihood of receiving high-intensity EoL care were increased comorbidity burden (odds ratio [OR]:1.29; 95% confidence interval [CI]:1.28-1.30), female sex (OR:1.05; 95% CI:1.01-1.09), Black race (OR:1.14; 95% CI:1.07-1.23), Other race/ethnicity (OR:1.20; 95% CI:1.10-1.30), stage III disease (OR:1.11; 95% CI:1.05-1.18), living in a county with >1,000,000 people (OR:1.23; 95% CI:1.16-1.31), living in a census tract with 10%-<20% poverty (OR:1.09; 95% CI:1.03-1.16) or 20%-100% poverty (OR:1.12; 95% CI:1.04-1.19), and having state-subsidized Medicare premiums (OR:1.18; 95% CI:1.12-1.24). The risk of high-intensity EoL care was lower among patients who were older (OR:0.98; 95% CI:0.98-0.99), lived in the Midwest (OR:0.69; 95% CI:0.65-0.75), South (OR:0.70; 95% CI:0.65-0.74), or West (OR:0.81; 95% CI:0.77-0.86), lived in mostly rural areas (OR:0.92; 95% CI:0.86-1.00), and had poor performance status (OR:0.26; 95% CI:0.25-0.28). Results were largely consistent across cancer types. DISCUSSION: The risk factors identified in our study can inform the development of new interventions for patients with cancer who are likely to receive high-intensity EoL care. Health systems should consider incorporating these risk factors into decision-support tools to assist clinicians in identifying which patients should be referred to hospice and palliative care.

Incidence and predictors of idiopathic pneumonia syndrome in hematopoietic stem cell transplant patients: a nationwide registry study.

Idiopathic pneumonia syndrome (IPS) is a rare but deadly complication of hematopoietic stem cell transplantation (HSCT). This study characterized the incidence and risk factors for IPS after HSCT in Taiwan. Data from January 2009 to February 2019 was collected from the Taiwan Society of BMT national registry. Forty-three (1.1%) of 3924 HSCT patients who developed IPS were identified. Incidence of IPS was lower in patients who received autologous HSCT than patients who received allogeneic HSCT (0.68% vs 1.44%, P = 0.022). Multivariate analysis showed that use of TBI and intravenous busulfan in the conditioning regimen were each independent predictor of IPS after HSCT. In addition, development of IPS was significantly associated with increased risk of death in the first 120 days post-HSCT (HR, 2.09; 95% CI, 1.08 to 4.05, P = 0.029) and 2 years post-HSCT (HR, 1.65; 95% CI, 1.07 to 2.542, P = 0.023), but not beyond 2 years post-HSCT. However, survival outcomes did not differ significantly between patients with IPS who received autologous versus allogeneic HSCT (P = 0.52). In conclusion, despite the relatively low incidence of post-HSCT IPS in Taiwan, mortality remains high. The results of this study will help to identify high-risk patients for early intervention and guide future therapeutic research.

Functional Status and Survival in Older Nursing Home Residents With Advanced Non-Small-Cell Lung Cancer: A SEER-Medicare Analysis.

PURPOSE: Many older patients with advanced lung cancer have functional limitations and require skilled nursing home care. Function, assessed using activities of daily living (ADL) scores, may help prognostication. We investigated the relationship between ADL impairment and overall survival among older patients with advanced non-small-cell lung cancer (NSCLC) receiving care in nursing homes. METHODS: Using the SEER-Medicare database linked with Minimum Data Set assessments, we identified patients age 65 years and older with NSCLC who received care in nursing homes from 2011 to 2015. We used Cox regression and Kaplan-Meier survival curves to examine the relationship between ADL scores and overall survival among all patients; among patients who received systemic cancer chemotherapy or immunotherapy within 3 months of NSCLC diagnosis; and among patients who did not receive any treatment. RESULTS: We included 3,174 patients (mean [standard deviation] age, 77 [7.4] years [range, 65-102 years]; 1,664 [52.4%] of female sex; 394 [12.4%] of non-Hispanic Black race/ethnicity), 415 (13.1%) of whom received systemic therapy, most commonly with carboplatin-based regimens (n = 357 [86%] patients). The median overall survival was 3.1 months for patients with ADL score < 14, 2.8 months for patients with ADL score between 14 and 17, 2.3 months for patients with ADL score between 18-19, and 1.8 months for patients with ADL score 20+ (log-rank P < .001). The ADL score was associated with increased risk of death (hazard ratio [HR], 1.20; 95% CI, 1.16 to 1.25 per standard deviation). One standard deviation increase in the ADL score was associated with lower overall survival rate among treated (HR, 1.14; 95% CI, 1.02 to 1.27) and untreated (HR, 1.20; 95% CI, 1.15 to 1.26) patients. CONCLUSION: ADL assessment stratified mortality outcomes among older nursing home adults with NSCLC, and may be a useful clinical consideration in this population.

Validation of a Post-Transplant Lymphoproliferative Disorder Risk Prediction Score and Derivation of a New Prediction Score Using a National Bone Marrow Transplant Registry Database.

BACKGROUND: We externally validated Fujimoto's post-transplant lymphoproliferative disorder (PTLD) scoring system for risk prediction by using the Taiwan Blood and Marrow Transplant Registry Database (TBMTRD) and aimed to create a superior scoring system using machine learning methods. MATERIALS AND METHODS: Consecutive allogeneic hematopoietic cell transplant (HCT) recipients registered in the TBMTRD from 2009 to 2018 were included in this study. The Fujimoto PTLD score was calculated for each patient. The machine learning algorithm, least absolute shrinkage and selection operator (LASSO), was used to construct a new score system, which was validated using the fivefold cross-validation method. RESULTS: We identified 2,148 allogeneic HCT recipients, of which 57 (2.65%) developed PTLD in the TBMTRD. In this population, the probabilities for PTLD development by Fujimoto score at 5 years for patients in the low-, intermediate-, high-, and very-high-risk groups were 1.15%, 3.06%, 4.09%, and 8.97%, respectively. The score model had acceptable discrimination with a C-statistic of 0.65 and a near-perfect moderate calibration curve (HL test p = .81). Using LASSO regression analysis, a four-risk group model was constructed, and the new model showed better discrimination in the validation cohort when compared with The Fujimoto PTLD score (C-statistic: 0.75 vs. 0.65). CONCLUSION: Our study demonstrated a more comprehensive model when compared with Fujimoto's PTLD scoring system, which included additional predictors identified through machine learning that may have enhanced discrimination. The widespread use of this promising tool for risk stratification of patients receiving HCT allows identification of high-risk patients that may benefit from preemptive treatment for PTLD. IMPLICATIONS FOR PRACTICE: This study validated the Fujimoto score for the prediction of post-transplant lymphoproliferative disorder (PTLD) development following hematopoietic cell transplant (HCT) in an external, independent, and nationally representative population. This study also developed a more comprehensive model with enhanced discrimination for better risk stratification of patients receiving HCT, potentially changing clinical managements in certain risk groups. Previously unreported risk factors associated with the development of PTLD after HCT were identified using the machine learning algorithm, least absolute shrinkage and selection operator, including pre-HCT medical history of mechanical ventilation and the chemotherapy agents used in conditioning regimen.

Temporal Trends in Sepsis Incidence and Mortality in Patients With Cancer in the US Population.

BACKGROUND: Few population-based studies assess the impact of cancer on sepsis incidence and mortality. OBJECTIVES: To evaluate epidemiological trends of sepsis in patients with cancer. METHODS: This retrospective cohort study included adults (≥20 years old) identified using sepsis-indicator International Classification of Diseases codes from the Nationwide Inpatient Sample database (2006-2014). A generalized linear model was used to trend incidence and mortality. Outcomes in patients with cancer and patients without cancer were compared using propensity score matching. Cox regression modeling was used to calculate hazard ratios for mortality rates. RESULTS: The study included 13 996 374 patients, 13.6% of whom had cancer. Gram-positive infections were most common, but the incidence of gram-negative infections increased at a greater rate. Compared with patients without cancer, those with cancer had significantly higher rates of lower respiratory tract (35.0% vs 31.6%), intra-abdominal (5.5% vs 4.6%), fungal (4.8% vs 2.9%), and anaerobic (1.2% vs 0.9%) infections. Sepsis incidence increased at a higher rate in patients with cancer than in those without cancer, but hospital mortality rates improved equally in both groups. After propensity score matching, hospital mortality was higher in patients with cancer than in those without cancer (hazard ratio, 1.25; 95% CI, 1.24-1.26). Of patients with sepsis and cancer, those with lung cancer had the lowest survival (hazard ratio, 1.65) compared with those with breast cancer, who had the highest survival. CONCLUSIONS: Cancer patients are at high risk for sepsis and associated mortality. Research is needed to guide sepsis monitoring and prevention in patients with cancer.

Gait speed, grip strength, and clinical outcomes in older patients with hematologic malignancies.

This study aimed to evaluate whether gait speed and grip strength predicted clinical outcomes among older adults with blood cancers. We prospectively recruited 448 patients aged 75 years and older presenting for initial consultation at the myelodysplastic syndrome/leukemia, myeloma, or lymphoma clinic of a large tertiary hospital, who agreed to assessment of gait and grip. A subset of 314 patients followed for ≥6 months at local institutions was evaluated for unplanned hospital or emergency department (ED) use. We used Cox proportional hazard models calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for survival, and logistic regression to calculate odds ratios (ORs) for hospital or ED use. Mean age was 79.7 (± 4.0 standard deviation) years. After adjustment for age, sex, Charlson comorbidity index, cognition, treatment intensity, and cancer aggressiveness/type, every 0.1-m/s decrease in gait speed was associated with higher mortality (HR, 1.20; 95% CI, 1.12-1.29), odds of unplanned hospitalizations (OR, 1.33; 95% CI, 1.16-1.51), and ED visits (OR, 1.34; 95% CI, 1.17-1.53). Associations held among patients with good Eastern Cooperative Oncology Group performance status (0 or 1). Every 5-kg decrease in grip strength was associated with worse survival (adjusted HR, 1.24; 95% CI, 1.07-1.43) but not hospital or ED use. A model with gait speed and all covariates had comparable predictive power to comprehensive validated frailty indexes (phenotype and cumulative deficit) and all covariates. In summary, gait speed is an easily obtained "vital sign" that accurately identifies frailty and predicts outcomes independent of performance status among older patients with blood cancers.

Function, Survival, and Care Utilization Among Older Adults With Hematologic Malignancies.

BACKGROUND/OBJECTIVES: Cancer-focused organizations now recommend routine assessment of instrumental activities of daily living (iADLs) for all older patients with cancer, along with assessment of basic activities of daily living (ADLs) if possible. However, little is known regarding the role of iADLs in predicting survival and acute-care utilization in populations of older adults with different hematologic malignancies. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: A screening geriatric assessment was conducted for adults 75 years and older with hematologic malignancies (n = 464) presenting for initial consultation at a large tertiary cancer hospital in Boston, MA. MEASUREMENTS: Univariable and multivariable analyses assessed the association of dependency in ADLs and dependency in iADLs with survival and care utilization (emergency department [ED] visits and unplanned hospitalizations). RESULTS: Subjects were a mean age of 79.7 years and had a mean follow-up of 13.8 months. Overall, 11.4% had dependency in ADLs and 26.7% had dependency in iADLs. Only iADL dependency was associated with higher mortality (hazard ratio = 2.34 [95% confidence interval [CI] = 1.46-3.74]) independently of age, comorbidity, cancer aggressiveness, and treatment intensity. The effect was dose dependent, and impairments in shopping, meal preparation, and housework were all independently associated with a higher hazard of death. iADL dependency was also associated with higher odds of ED visits (odds ratio [OR] = 2.76 [95% CI = 1.30-5.84]) and hospitalizations (OR = 2.89 [95% CI = 1.37-6.09]). Several geriatric domain impairments, including probable cognitive impairment and physical dysfunction, were associated with iADL dependency. CONCLUSION: These findings suggest that older adults with hematologic malignancies and iADL dependency experience higher mortality and acute-care utilization, arguing that iADLs should be formally assessed as part of routine oncology care. J Am Geriatr Soc 67:889-897, 2019.

Rare side effect of adjuvant ipilimumab after surgical resection of melanoma: Guillain-Barré syndrome.

Guillain-Barré syndrome is a life-threatening neurological disorder that presents with rapid ascending paralysis and areflexia. Guillain-Barré syndrome is traditionally associated with infections from a gastrointestinal or respiratory tract source. We report the case of a 71-year-old man with melanoma who was treated with ipilimumab as adjuvant immunotherapy and subsequently developed Guillain-Barré syndrome. The diagnosis was made clinically through physical exam findings. He was successfully treated with a combination of intravenous immunoglobulin therapy and corticosteroids.

Relationship between physician and patient assessment of performance status and survival in a large cohort of patients with haematologic malignancies.

BACKGROUND: Few studies have investigated the relationship between physician and patient-assessed performance status (PS) in blood cancers. METHODS: Retrospective analysis among 1418 patients with haematologic malignancies seen at Dana-Farber Cancer Institute between 2007 and 2014. We analysed physician-patient agreement of Eastern Cooperative Oncology Group PS using weighted κ-statistics and survival analysis. RESULTS: Mean age was 58.6 years and average follow-up was 38 months. Agreement in PS was fair/moderate (weighted κ=0.41, 95% CI 0.37-0.44). Physicians assigned a better functional status (lower score) than patients (mean 0.60 vs 0.81), particularly when patients were young and the disease was aggressive. Both scores independently predicted survival, but physician scores were more accurate. Disagreements in score were associated with poorer survival when physicians rated PS better than patients, and were modified by age, sex and severity of disease. CONCLUSIONS: Physician-patient disagreements in PS score are common and have prognostic significance.

Association of lung function with coronary heart disease and cardiovascular disease outcomes in elderly: the Rancho Bernardo study.

INTRODUCTION: Lung function is inversely associated with coronary heart disease (CHD) and cardiovascular disease (CVD). We evaluated the prospective association of reduced lung function by spirometry and CHD or CVD events in older community-dwelling adults. METHODS: We studied 1548 participants (mean age 73.6 ± 9.2 years, 42% males) from the Rancho Bernardo Study using age, sex, and risk-factor adjusted Cox regression to assess pulmonary function (FEV1, FVC, and FEV1/FVC ratio) as a predictor of CHD and CVD events followed for up to 22 years. RESULTS: Of CVD risk factors, older age, male sex, current/past smoking, physical exercise (<3× a week), and prevalent CVD predicted an increased risk of CHD and CVD. Higher FEV1 and FVC were each associated with a decreased risk of CHD [HR 0.80 (0.73-0.88) for both FEV1 and FVC, per SD, p < 0.01] and CVD [HR 0.82 (0.74-0.91) for both FEV1 and FVC, per SD, p < 0.01]. Those in the lowest quartiles of FEV1 and FVC had hazard ratios of 1.68 (1.33-2.13) and 1.55 (1.21-2.00) respectively for CHD and 1.74 (1.34-2.25) and 1.49 (1.13-1.96) respectively for CVD (all p < 0.01, relative to those in the highest quartile). Similar findings were observed for CHD and CVD mortality. Sex- and age-stratified analyses showed the strongest associations for CHD and CVD events in women and in the oldest participants. CONCLUSIONS: FEV1 and FVC are inversely associated with risk of future CHD and CVD events in older community-dwelling adults and may add to CVD risk stratification in the elderly.