The association between HLA and non-Hodgkin lymphoma subtypes, among a transplant-indicated population.

Several studies have implicated HLA in non-Hodgkin lymphoma (NHL) subtype etiology. However, NHL patients indicated for stem cell transplants are underrepresented in these reports. We therefore evaluated the association between HLA and NHL subtypes among a transplant-indicated population. One thousand three hundred and sixty-six NHL patients HLA-typed and indicated for transplant at the City of Hope National Medical Center (Duarte, CA) were compared to 10,271 prospective donors. Odds ratios and 95% confidence intervals were calculated for HLA haplotype and alleles, adjusted for sex and age. The HLA-A*0201∼C*0602∼B*1302∼DRB1*0701∼DQB1*0201 haplotype was significantly associated with follicular lymphoma (FL) risk among Caucasians. Several haplotypes were associated with diffuse large B-cell lymphoma (DLBCL) risk among Caucasians, including the previously implicated DLBCL risk loci, HLA-B*0801. The HLA-A*0101 allele was also observed to be associated with mantle cell lymphoma (MCL) risk. Our results support the association between previously reported susceptibility loci and FL and suggest potentially new DLBCL and MCL risk loci.

Prophylactic Pancreatectomies Carry Prohibitive Mortality at Low-Volume Centers: A California Cancer Registry Study.

BACKGROUND: Pancreatectomy for malignancy is associated with improved outcomes when performed at high-volume centers. The goal of this study was to assess pancreatectomy outcomes for premalignant cystic lesions as a function of hospital volume. METHODS: The Healthcare Cost and Utilization Project (HCUP) was queried for all pancreatectomies performed in California from 2003 to 2011. Cases were stratified, separating benign versus malignant disease. Hospitals were categorized as low-volume (≤25 pancreatectomies/year; LV) or high-volume (>25; HV) centers. Perioperative morbidity, mortality, and length of stay were compared in HV vs. LV centers. RESULTS: There were 7554 pancreatectomies performed in 201 hospitals during the study period, where 5652 (75%) procedures were performed for malignancy, 338 (4%) for chronic pancreatitis, and 1564 (21%) for benign/premalignant cysts. The majority of pancreatectomies for cystic disease were performed at LV centers (65%). There were no significant differences in length of stay (7 vs. 8 days; p = 0.6) or 90-day readmission rates (12.8% vs. 12.9%; p = 1.0) in HV versus LV centers. However, there were higher surgical (46.2% LV vs. 41.1% HV, p = 0.05) and medical (13.3% LV vs. 9.2% HV; p = 0.017) complications at LV centers. Most importantly, there was a fourfold higher in-hospital mortality at LV centers (2.36% vs. 0.55%; p = 0.007). CONCLUSION: Pancreatic resection for benign lesions at HV hospitals is associated with significantly lower morbidity and mortality, suggesting that when feasible, patients should seek care at high-volume centers for these semi-elective surgeries.

Understanding Caregiver Quality of Life in Caregivers of Hospitalized Older Adults With Cancer.

BACKGROUND/OBJECTIVES: Caregivers of older adults with cancer assist both with cancer care and other health issues, which may make them vulnerable to consequences of caregiving. Hospitalization may represent a time when a caregiver's ability to provide care at home is exceeded. We sought to characterize caregivers of hospitalized older adults with cancer, determine their quality of life (QOL), and identify factors associated with caregiver QOL. METHODS: Patients (n = 100), aged 65 years and older, with an unplanned hospitalization and their caregivers were included. Caregivers completed a questionnaire about their health, social support, caregiving relationship, QOL (Caregiver Quality of Life Index-Cancer [CQOLC] tool), and patient function. Patient medical history was obtained via chart review. The association between patient, caregiving, and caregiver factors and CQOLC was determined using multivariate linear regression. RESULTS: Most patients (73%) had metastatic/advanced disease, and 71% received treatment for their cancer within 30 days of hospitalization. Median Karnofsky Performance Status (KPS) was 60%, and 89% required help with instrumental activities of daily living, as reported by caregivers. Median caregiver age was 65 years (range = 29-84 years). The majority (60%) had no major comorbidities and rated their health as excellent/good (79%), though 22% reported worsening health due to caregiving. Caregivers had a median Mental Health Inventory-18 score of 70 (range = 0-97), a median Medical Outcomes Study (MOS)-social activity score of 56 (range = 0-87.5), and a median MOS-Social Support Survey score of 68 (range = 0-100). Caregivers provided a median of 35 hours of care per week (range = 0-168 hours of care per week). Mean CQOLC was 84.6 ± 23.5. Lower caregiver QOL was associated with poorer caregiver mental health, less social support, and poorer patient KPS (P < .05). CONCLUSION: Caregivers of hospitalized older adults with cancer are older but generally in good health. Those with poorer mental health, less social support, and caring for patients with poorer performance status are more likely to experience lower QOL. J Am Geriatr Soc 67:978-986, 2019.

Human Neural Stem Cell Biodistribution and Predicted Tumor Coverage by a Diffusible Therapeutic in a Mouse Glioma Model.

Engineered neural stem cells (NSCs) intrinsically migrating to brain tumors offer a promising mechanism for local therapeutic delivery. However, difficulties in quantitative assessments of NSC migration and in estimates of tumor coverage by diffusible therapeutics have impeded development and refinement of NSC-based therapies. To address this need, we developed techniques by which conventional serial-sectioned formalin-fixed paraffin-embedded (FFPE) brains can be analyzed in their entirety across multiple test animals. We considered a conventional human glioblastoma model: U251 glioma cells orthotopically engrafted in immunodeficient mice receiving intracerebral (i.c.) or intravenous (i.v.) administrations of NSCs expressing a diffusible enzyme to locally catalyze chemotherapeutic formation. NSC migration to tumor sites was dose-dependent, reaching 50%-60% of total administered NSCs for the i.c route and 1.5% for the i.v. route. Curiously, the most efficient NSC homing was seen with smaller NSC doses, implying existence of rate-limiting process active during administration and/or migration. Predicted tumor exposure to a diffusing therapeutic (assuming a 50 µm radius of action) could reach greater than 50% of the entire tumor volume for i.c. and 25% for i.v. administration. Within individual sections, coverage of tumor area could be as high as 100% for i.c. and 70% for i.v. routes. Greater estimated therapeutic coverage was observed for larger tumors and for larger tumor regions in individual sections. Overall, we have demonstrated a framework within which investigators may rationally evaluate NSC migration to, and integration into, brain tumors, and therefore enhance understanding of mechanisms that both promote and limit this therapeutic modality. Stem Cells Translational Medicine 2017;6:1522-1532.

Optimization of a Neural Stem-Cell-Mediated Carboxylesterase/Irinotecan Gene Therapy for Metastatic Neuroblastoma.

Despite improved survival for children with newly diagnosed neuroblastoma (NB), recurrent disease is a significant problem, with treatment options limited by anti-tumor efficacy, patient drug tolerance, and cumulative toxicity. We previously demonstrated that neural stem cells (NSCs) expressing a modified rabbit carboxylesterase (rCE) can distribute to metastatic NB tumor foci in multiple organs in mice and convert the prodrug irinotecan (CPT-11) to the 1,000-fold more toxic topoisomerase-1 inhibitor SN-38, resulting in significant therapeutic efficacy. We sought to extend these studies by using a clinically relevant NSC line expressing a modified human CE (hCE1m6-NSCs) to establish proof of concept and identify an intravenous dose and treatment schedule that gave maximal efficacy. Human-derived NB cell lines were significantly more sensitive to treatment with hCE1m6-NSCs and irinotecan as compared with drug alone. This was supported by pharmacokinetic studies in subcutaneous NB mouse models demonstrating tumor-specific conversion of irinotecan to SN-38. Furthermore, NB-bearing mice that received repeat treatment with intravenous hCE1m6-NSCs and irinotecan showed significantly lower tumor burden (1.4-fold, p = 0.0093) and increased long-term survival compared with mice treated with drug alone. These studies support the continued development of NSC-mediated gene therapy for improved clinical outcome in NB patients.

Modeling longitudinal data and its impact on survival in observational nephrology studies: tools and considerations.

Nephrologists and kidney disease researchers are often interested in monitoring how patients' clinical and laboratory measures change over time, what factors may impact these changes, and how these changes may lead to differences in morbidity, mortality, and other outcomes. When longitudinal data with repeated measures over time in the same patients are available, there are a number of analytical approaches that could be employed to describe the trends and changes in these measures, and to explore the associations of these changes with outcomes. Researchers may choose a streamlined and simplified analytic approach to examine trajectories with subsequent outcomes such as estimating deltas (subtraction of the last observation from the first observation) or estimating per patient slopes with linear regression. Conversely, they could more fully address the data complexity by using a longitudinal mixed model to estimate change as a predictor or employ a joint model, which can simultaneously model the longitudinal effect and its impact on an outcome such as survival. In this review, we aim to assist nephrologists and clinical researchers by reviewing these approaches in modeling the association of longitudinal change in a marker with outcomes, while appropriately considering the data complexity. Namely, we will discuss the use of simplified approaches for creating predictor variables representing change in measurements including deltas and patient slopes, as well more sophisticated longitudinal models including joint models, which can be used in addition to simplified models based on the indications and objectives of the study as warranted.

Timing and severity of post-discharge morbidity after hepatectomy.

BACKGROUND: In order to decrease cost and increase healthcare quality there is an ongoing effort to reduce readmissions after complex operations. The timing and severity of post-discharge complications after hepatectomy need to be better defined. METHODS: All patients undergoing liver resection at a single institution from Jan 2009-Jun 2015 were included. Complications were scored using the comprehensive complication index (CCI). Multivariate analysis is performed using logistic regression. Receiver operating characteristics (ROCs) were analyzed to optimize the Readmission Risk Index (RRI). RESULTS: Of the 258 patients that met the inclusion criteria, 26 (10%) were readmitted within 30 days of discharge after hepatectomy. On multivariate analysis age ≥68 years (OR 3.76; 95% CI 1.47-9.63, p = 0.006), CCI ≥ 15 (OR 3.65; 95% CI 1.39-9.56, p = 0.008), maximum temperature within 48 h of discharge (OR 3.02; 95% CI 1.17-7.75, p = 0.022) and white blood cell count ≥10.2 billion cells/L within 48 h of discharge (OR 2.88; 95% CI 1.04-8, p = 0.043) were independent predictors of 30-day readmission. These variables were used to develop the RRI (ROC area 0.80; 95% CI 0.70-0.9, p < 0.001). CONCLUSION: The CCI and pre-discharge variables can help identify individuals at risk of readmission. Readmission risk reduction efforts should focus on this subset of patients.

Reliability, Validity, and Feasibility of a Computer-Based Geriatric Assessment for Older Adults With Cancer.

PURPOSE: The goal of this study was to evaluate the feasibility, reliability, and validity of a computer-based geriatric assessment via two methods of electronic data capture ( SupportScreen and REDCap) compared with paper-and-pencil data capture among older adults with cancer. METHODS: Eligible patients were ≥ 65 years old, had a cancer diagnosis, and were fluent in English. Patients were randomly assigned to one of four arms, in which they completed the geriatric assessment twice: (1) REDCap and paper and pencil in sessions 1 and 2; (2) REDCap in both sessions; (3) SupportScreen and paper and pencil in sessions 1 and 2; and (4) SupportScreen in both sessions. The feasibility, reliability, and validity of the computer-based geriatric assessment compared with paper and pencil were evaluated. RESULTS: The median age of participants (N = 100) was 71 years (range, 65 to 91 years) and the diagnosis was solid tumor (82%) or hematologic malignancy (18%). For session 1, REDCap took significantly longer to complete than paper and pencil (median, 21 minutes [range, 11 to 44 minutes] v median, 15 minutes [range, 9 to 29 minutes], P < .01) or SupportScreen (median, 16 minutes [range, 6 to 38 minutes], P < .01). There were no significant differences in completion times between SupportScreen and paper and pencil ( P = .50). The computer-based geriatric assessment was feasible. Few participants (8%) needed help with completing the geriatric assessment (REDCap, n = 7 and SupportScreen, n = 1), 89% reported that the length was "just right," and 67% preferred the computer-based geriatric assessment to paper and pencil. Test-retest reliability was high (Spearman correlation coefficient ≥ 0.79) for all scales except for social activity. Validity among similar scales was demonstrated. CONCLUSION: Delivering a computer-based geriatric assessment is feasible, reliable, and valid. SupportScreen methodology is preferred to REDCap.

Predictors of Antiestrogen Recommendation in Women With Estrogen Receptor-Positive Ductal Carcinoma In Situ.

BACKGROUND: Antiestrogen (anti-e) use in estrogen receptor-positive (ER+) ductal carcinoma in situ (DCIS) has been shown to reduce the incidence of noninvasive and invasive breast cancer. Few studies have evaluated factors associated with anti-e recommendation in ER+ DCIS. METHODS: The California Cancer Registry was queried for female patients diagnosed with ER+ DCIS and treated with lumpectomy or unilateral mastectomy from 2004 to 2011. Patient demographics, comorbidities, and clinical characteristics were analyzed for association with anti-e recommendation. RESULTS: Of 5,527 patients identified, 76.4% patients underwent lumpectomy and 23.6% underwent unilateral mastectomy. Of the total cohort, 31.6% patients were recommended anti-e therapy, 60.4% were not, and the remaining 8.0% were recommended anti-e, but administration was not documented. Performance of lumpectomy predicted anti-e use compared with mastectomy (odds ratio [OR], 2.08; 95% CI, 1.77-2.43). Asian/Pacific Islanders were more often recommended anti-e therapy when compared with whites (OR, 1.28; 95% CI, 1.10-1.49). Patients younger than 70 years were more often recommended anti-e (age, 18-49 years: OR, 1.38; CI, 1.12-1.71; and age, 50-69 years: OR, 1.43; CI, 1.20-1.71). CONCLUSIONS: Despite current guidelines to consider the use of anti-e therapy, recommendation of anti-e after surgical treatment of DCIS is low, having been recommended to 40% of patients, and used by fewer than one-third. Significant predictors include lumpectomy compared with unilateral mastectomy, Asian/Pacific Islander race, younger age, and number of comorbidities. Further work is merited to understand patterns of anti-e therapy recommendation by providers in patients with DCIS.

Evaluation of innate and adaptive immunity contributing to the antitumor effects of PD1 blockade in an orthotopic murine model of pancreatic cancer.

Despite the clinical success of anti-PD1 antibody (α-PD1) therapy, the immune mechanisms contributing to the antineoplastic response remain unclear. Here, we describe novel aspects of the immune response involved in α-PD1-induced antitumor effects using an orthotopic Kras (G12D)/p53(R172H)/Pdx1-Cre (KPC) model of pancreatic ductal adenocarcinoma (PDA). We found that positive therapeutic outcome involved both the innate and adaptive arms of the immune system. Adoptive transfer of total splenocytes after short-term (3 d) but not long-term (28 d) PD1 blockade significantly extended survival of non-treated tumor-bearing recipient mice. This protective effect appeared to be mostly mediated by T cells, as adoptive transfer of purified natural killer (NK) cells and/or granulocyte receptor 1 (Gr1)(+) cells or splenocytes depleted of Gr1(+) cells and NK cells did not exhibit transferrable antitumor activity following short-term PD1 blockade. Nevertheless, splenic and tumor-derived CD11b(+)Gr1(+) cells and NK cells showed significant persistence of α-PD1 bound to these cells in the treated primary recipient mice. We observed that short-term inhibition of PD1 signaling modulated the profiles of multifunctional cytokines in the tumor immune-infiltrate, including downregulation of vascular endothelial growth factor A (VEGF-A). Altogether, the data suggest that systemic blockade of PD1 results in rapid modulation of antitumor immunity that differs in the tumor microenvironment (TME) when compared to the spleen. These results demonstrate a key role for early immune-mediated events in controlling tumor progression in response to α-PD1 treatment and warrant further investigation into the mechanisms governing responses to the therapy at the innate-adaptive immune interface.

Proportion of Non-Small-Cell Lung Cancer Patients that Would Have Been Eligible for Lung Cancer Screening.

BACKGROUND: Lung cancer screening is recommended for current smokers (CS) and former smokers (FS) who meet specific age and smoking criteria. We used existing criteria to estimate the proportion of non-small-cell lung cancer (NSCLC) patients that would have been screening-eligible. METHODS: We identified 2030 NSCLC patients at our institution from 1994 to 2014 and recorded their cigarette smoking status and history. Using criteria from the United States Preventative Services Task Force (USPSTF) and from other organizations, we ascertained the proportions of screening-eligible patients. Associations among smoking status, gender, race/ethnicity, and insurance type were assessed using Chi-Square test. RESULTS: In our cohort, 31.0% (n = 630) were CS, 43.0% (n = 873) were FS, and 26.0% (n = 527) were never smokers. There were 698 patients (34.4%) who met all USPSTF screening criteria. Among 1503 CS and FS, 77.5% (n = 1165) were between age 55 and 80 years, and 67.9% (n = 1021) had smoked ≥ 30 pack-years. Among FS, 50.4% (n = 440) had quit within 15 years of diagnosis. Median pack-years smoked was 40 (interquartile range, 20-55 pack-years). CS were more likely to meet screening criteria than FS (67.5% vs. 31.3%; P < .0001). Significant differences were found among individuals meeting criteria by gender, race/ethnicity, and insurance type. CONCLUSION: Only a third of patients diagnosed with NSCLC were eligible for lung cancer screening based on USPSTF criteria. FS were less likely to meet all screening criteria due to only half meeting the quit-time criterion. Additional evidence is needed to evaluate the utility of restricting screening among FS to those who quit within 15 years.

Influence of Hormone Receptor Status on Spinal Metastatic Lesions in Patients with Breast Cancer.

OBJECTIVE: Bony metastasis predominantly affects the spinal column and has been commonly associated in patients with breast cancer. There are two types of lesions that can occur with spine cancer-osteolytic or osteoblastic. Some patients may have mixed lesions, which include lytic and blastic in one vertebra or lytic and blastic in different vertebrae. Previous studies have shown that patients with breast cancer have an increased likelihood for development of lytic spinal metastases. METHODS: A retrospective chart review was conducted to more closely examine the association between hormone receptor status and spinal lesion type. A total of 195 patients were initially identified through the City of Hope Cancer Registry. Of the 195, only 153 patients had hormone receptor marker status available. Associations between spinal lesion and hormone receptor status were evaluated using χ(2) tests with alpha = 0.05 significance level. In a secondary analysis, the Oncomine Platform was used, which integrated The Cancer Genome Atlas (TCGA) datasets, to identify osteogenic genes that may be relevant to invasive breast cancers. RESULTS: Contrary to previous studies, our findings revealed progesterone receptor positive (PR+) patients were significantly more likely to present with blastic than lytic or mixed lesions. Furthermore, using TCGA analysis, COL1A1 and COL1A2 were found to be up-regulated, which could provide a molecular explanation for the development of blastic metastases. CONCLUSIONS: By integrating clinical and bioinformatic techniques, this study provides a novel discovery of the relationship between blastic and PR + breast cancers, which may have important implications for diagnostic strategies concerning vertebral metastases.

Patterns and Trends in Immediate Postmastectomy Reconstruction in California: Complications and Unscheduled Readmissions.

BACKGROUND: Immediate reconstruction rates after mastectomy are increasing but remain low. Little is known about hospital readmissions after these procedures. The authors studied unscheduled readmissions after immediate reconstruction. METHODS: Using the Healthcare Cost and Utilization Project California State database, the authors identified patients undergoing mastectomy only or with immediate reconstruction for ductal carcinoma in situ and invasive breast cancer from 2005 to 2009. Immediate reconstruction included tissue expander/implant and autologous tissue reconstructions. The authors evaluated temporal trends in immediate reconstruction and factors associated with 30-day unscheduled readmissions after reconstruction. RESULTS: The cohort contained 48,414 patients (mastectomy only, 35,648; immediate reconstruction, 12,766; tissue expander/implant, 10,437; autologous tissue, 2329). Readmission rates were not significantly different between mastectomy only and immediate reconstruction (3.55 percent versus 3.39 percent; p = 0.39); however, autologous tissue reconstruction was associated with a significantly higher readmission rate compared with tissue expander/implant reconstruction (4.08 percent versus 3.24 percent; p = 0.04). CONCLUSIONS: Immediate reconstruction does not result in higher readmission rates compared with mastectomy only. All women undergoing mastectomy should be offered consultation for reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Modeling absolute lymphocyte counts after treatment of chronic lymphocytic leukemia with ibrutinib.

The objective in this study was to characterize the pattern of the treatment-related lymphocytosis curve in chronic lymphocytic leukemia (CLL) patients treated with ibrutinib, and assess the relationship between the baseline factors and absolute lymphocyte counts (ALC). The PCYC-1102-CA study was a five-arm phase Ib/II open-label, nonrandomized, multicenter study in CLL/SLL. The arms and accruals were 420 and 840 mg/day treatment-naive elderly CLL/SLL (N = 27 and N = 4, respectively), 420 and 840 mg/day relapsed/refractory CLL/SLL (N = 27 and N = 34, respectively), and 420 mg/day high-risk CLL/SLL (N = 24). The results were generated through statistical modeling using data from a clinical trial (PCYC-1102) in five cohorts of treatment-naïve or relapsed/refractory CLL patients treated at 420 and 840 mg daily of ibrutinib. In cases in which the initial increase in ALC doubles by day 28, it takes patients longer to reach their maximum ALC when compared with those with a lower rate of increase. Our models show that all of the cohorts exhibited the same pattern of treatment-related lymphocytosis from ibrutinib, and there are no significant differences between cohorts, including no detectable dose effect. The ALC of the majority of patients return to baseline ALC values by the end of cycle 5.

Life expectancy after curative-intent treatment of breast cancer: impact on long-term follow-up care.

Long-term survival rates after treatment for breast cancer are directly influenced by early deaths resulting from disease. For longer-term breast cancer survivors, survival rates appear deceptively low. We hypothesize that the actual survival curve for long-term survivors approaches the overall survival of the general population. The Surveillance, Epidemiology, and End Results database (1988 to 2002) was used to identify patients with nonmetastatic breast cancer who underwent definitive surgical treatment. The survival of the general population was constructed by using national life tables with an age-matched population. Comparisons of survivals were made for 3-, 5-, and 7-year breast cancer survivor cohorts. Of 237,180 patients, 92.4 per cent survived three years, 82.1 per cent five years, and 58.1 per cent seven years. Stage I patients have equivalent or better survivals compared with the age-matched general population in all three cohorts. Stage II patients reached equivalent conditional survival between eight and nine years after diagnosis regardless of cohort. Stage III patients required achieving nine to 10 years after diagnosis to achieve equivalent survival probability, except in 7-year survivors, in whom 10 to 11 years was required. In all stages, once equivalence was reached, survival exceeded the general population over the remaining years. Initial cancer stage influences overall survival for many years after diagnosis. Patients with Stage I cancer return to the general population risk as early as three years after diagnosis, whereas higher stages can require up to nine years to achieve parity with a more generalized population. These findings should be factored into general health screening issues for long-term breast cancer survivors.

Culture-Sensitive Question Order Effects of Self-Rated Health Between Older Hispanic and Non-Hispanic Adults in the United States.

OBJECTIVE: The aim of this study is to examine context effects created by the question order for self-rated health (SRH) by race/ethnicity and language. METHOD: Differences in SRH estimates for non-Hispanic Whites and Hispanics were first examined with multiple observational data that asked SRH in different contexts. To examine context effects by socio-demographics and health-related characteristics, we conducted experiments on SRH question order. RESULTS: While Hispanics reported poorer health than non-Hispanic Whites, this difference, in part, depended on question contexts. With SRH asked after rather than before specific health questions, Hispanics, especially Spanish-speaking Hispanics, reported better health, while non-Hispanic Whites' reports remained consistent. Among Spanish-speaking Hispanics, the context effect was larger for unmarried and less educated persons and those with comorbidities. DISCUSSION: Question contexts influence SRH reports by Spanish-speaking older adults. Cross-cultural inquiries on the meaning of health and its dynamics with question contexts may explain what SRH measures for increasingly diverse populations.

Trends in radiotherapy after breast-conserving surgery in elderly patients with early-stage breast cancer.

BACKGROUND: The benefit of adjuvant radiotherapy (RT) in elderly breast cancer patients is debatable. The purpose of this study was to evaluate trends in RT rates after breast-conserving surgery. METHODS: Breast cancer patients ≥70 years treated from 2000 to 2009 were identified using the Surveillance, Epidemiology, and End Results (SEER) database. Patients were estrogen receptor positive with negative or unknown lymph node status. Trends in RT recommendation over years were evaluated with the Jonckheere-Terpstra test. Multiple logistic regression and Cox proportional hazard tests were used to determine factors associated with radiation recommendation and survival. RESULTS: Of 46,581 patients, 31,989 (68.7 %) were recommended RT and 14,592 (31.3 %) were not. The recommendation for RT decreased from 70.3 % in 2000 to 67.4 % in 2009 (p < 0.0001). Seven of 18 registries exhibited decreased radiation recommendation rates, and 4 of 18 exhibited an increase. Recommendation of RT was associated with earlier year of diagnosis, younger age, Asian/Pacific Islander race, and negative lymph nodes. Predictors of worse survival were no radiation [hazard ratio (HR) 1.68, 95 % confidence interval (CI) 1.61-1.75], no nodes examined (HR 1.83, 95 % CI 1.75-1.91), large (>2-5 cm) tumor size (HR 2.02, 95 % CI 1.86-2.19), older age (80+, HR 2.38, 95 % CI 2.25-2.53), and black race (HR 1.13, 95 % CI1.03-1.23). CONCLUSIONS: Rates of radiation recommendation in the elderly have been steadily decreasing without appreciable acceleration in this decline. This trend was not consistent across all registries. Continued research is necessary to assess differences in clinical practice and its impact on patient outcomes.

Hyperphosphatemia is a combined function of high serum PTH and high dietary protein intake in dialysis patients.

Elevated serum phosphorus is associated with higher death risk in hemodialysis patients. Previous studies have suggested that both higher serum parathyroid hormone (PTH) level and higher dietary protein intake may contribute to higher serum phosphorus levels. However, it is not well known how these two factors simultaneously contribute to the combined risk of hyperphosphatemia in real patient-care scenarios. We hypothesized that the likelihood of hyperphosphatemia increases across higher serum PTH and higher normalized protein catabolic rate (nPCR) levels, a surrogate of protein intake. Over an 8-year period (July 2001-June 2009), we identified 69,355 maintenance hemodialysis patients with PTH, nPCR, and phosphorus data in a large dialysis provider. Logistic regression models were examined to assess the association between likelihood of hyperphosphatemia (serum phosphorus >5.5 mg/dl) and serum PTH and nPCR increments. Patients were 61±15 years old and included 46% women, 33% blacks, and 57% diabetics. Both higher serum PTH level and higher protein intake were associated with higher risk of hyperphosphatemia in dialysis patients. Compared with patients with PTH level 150-<300 pg/ml and nPCR level 1.0-<1.2 g/kg/day, patients with iPTH>600 pg/ml and nPCR>1.2 g/kg/day had a threefold higher risk of hyperphosphatemia (OR: 3.17, 95% CI: 2.69-3.75). Hyperphosphatemia is associated with both higher dietary protein intake and higher serum PTH level in maintenance hemodialysis patients. Worsening or resistant hyperphosphatemia may be an under-appreciated consequence of secondary hyperparathyroidism independent of dietary phosphorus load. Management of hyperphosphatemia should include diligent correction of hyper-parathyroidism while maintaining adequate intake of high protein foods with low phosphorus content.