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Purpose: We compared work outcomes in patients with oropharyngeal cancer (OPC), randomized to intensity-modulated proton (IMPT) versus intensity-modulated photon therapy (IMRT) for chemoradiation therapy (CRT)., Patients and Methods: In 147 patients with stage II-IVB squamous cell OPC participating in patient-reported outcomes assessments, a prespecified secondary aim of a randomized phase II/III trial of IMPT (n = 69) versus IMRT (n = 78), we compared absenteeism, presenteeism (i.e., the extent to which an employee is not fully functional at work), and work productivity losses. We used the work productivity and activity impairment questionnaire at baseline (pre-CRT), at the end of CRT, and at 6 months, 1 year, and 2 years. A one-sided Cochran-Armitage test was used to analyze within-arm temporal trends, and a χ 2 test was used to compare between-arm differences. Among working patients, at each follow-up point, a 1-sided Wilcoxon rank-sum test was used to compare work-productivity scores., Results: Patient characteristics in IMPT versus IMRT arms were similar. In the IMPT arm, within-arm analysis demonstrated that an increasing proportion of patients resumed working after IMPT, from 60% (40 of 67) pre-CRT and 71% (30 of 42) at 1 year to 78% (18 of 23) at 2 years ( P  = 0.025). In the IMRT arm, the proportion remained stable, with 57% (43 of 76) pre-CRT, 54% (21 of 39) at 1 year, and 52% (13 of 25) working at 2 years ( P  = 0.47). By 2 years after CRT, the between-arm difference between patients who had IMPT and those who had IMRT trended toward significance ( P  = 0.06). Regardless of treatment arm, among working patients, the most severe work impairments occurred from treatment initiation to the end of CRT, with significant recovery from absenteeism, presenteeism, and productivity impairments by the 2-year follow-up ( P  < 0.001 for all). Higher magnitudes of recovery from absenteeism (at 1 year, P  = 0.05; and at 2 years, P  = 0.04) and composite work impairment scores (at 1 year, P  = 0.04; and at 2 years, P  = 0.04) were seen in patients treated with IMPT versus those treated with IMRT., Conclusion: In patients with OPC receiving curative CRT, patients randomized to IMPT demonstrated increasing work and productivity recovery trends. Studies are needed to identify mechanisms underlying head and neck CRT treatment causing work disability and impairment., Competing Interests: Conflicts of Interest: Steven J. Frank, MD, is an Associate Editor of the International Journal of Particle Therapy. Dr Frank reports grants and personal fees from Hitachi. Outside the submitted work, Dr Frank is a cofounder of C4 Imaging, LLC, for which he reports grants and personal fees, and he reports grants from Eli Lilly and Elekta, other remuneration from Breakthrough Chronic Care, and personal fees from Varian, Augmenix, and the National Comprehensive Cancer Center (NCCN). The other authors have no conflicts of interest to disclose., (©Copyright 2021 The Author(s).)

Background: The immune system plays a crucial role in cancer surveillance. Previous studies have shown that lymphopenia associated with radiotherapy (RT) portends a poor prognosis. We sought to differentiate the effects of proton and photon RT on changes in absolute lymphocyte count (ALC) for patients with hepatocellular carcinoma (HCC)., Patients and Methods: Patients with HCC treated with definitive RT from 2006 to 2016 were studied. Serial ALCs were graded according to CTCAE v4.0. Overall survival (OS), disease-free survival, and distant metastasis-free survival were analyzed using the Kaplan-Meier method. Univariable and multivariable Cox-proportional hazards analyses were used to identify predictors of OS. A cohort analysis matched for treatment volume was performed to investigate differences in ALC dynamics between photon and proton therapy., Results: Of 143 patients identified, the median age was 66 (range, 19-90) years. The treatment modality was photon in 103 (72%) and proton in 40 (28%). Median follow-up was 17 months (95% confidence interval, 13-25 months). The median time to ALC nadir after initiation of RT was 17 days with a median relative decrease of 67%. Those who received proton RT had a higher median ALC nadir (0.41 vs 0.32 k/µL, p=0.002) and longer median OS (33 vs 13 months, p=0.002) than those who received photon RT. Matched cohort analyses revealed a larger low-dose liver volume in the photon group, which correlated with lower ALC. On multivariable Cox analysis, Grade 3 or higher lymphopenia prior to or after RT, portal venous tumor thrombus, larger planning target volumes, Child-Pugh (CP) Class B, and increased CP score after RT were associated with a higher risk of death, whereas the use of proton therapy was associated with lower risk., Conclusion: Grade 3 or higher lymphopenia may be associated with poorer outcomes in patients receiving RT for HCC. Protons may mitigate lymphopenia compared with photons, potentially due to reduced dose exposure of sites of lymphopoiesis., Competing Interests: BD reports honorarium from Sermo, Inc. ACK reports ownership of shares in Aravive, Inc. SPN reports funding from the Australian Postgraduate Award, the Royal Australian and New Zealand College of Radiologists (RANZCR) Research Grants, and the Radiological Society of North America (RSNA) Fellow Grant. JMH reports research support from Oncosil, Galera, Auro, and Augmenix and is also a consultant for BTG, AbbVie, Celgene, AstraZeneca, BMS, and Varian. RT reports personal fees from QED Therapeutics/The Lynx Group. EBH reports grants from Merck. SK reports grants from NIH, DoD, and CPRIT. In addition, SK reports a patent for minibeam therapy. TSH reports consulting fees from Merck, Novocure, Synthetic Biologics, and research funding from Taiho, Astra-Zeneca, BMS, Puma, IntraOp, and Tesaro. SHL reports grants and personal fees from Beyond Spring Pharmaceuticals and Hitachi Chemical Diagnostics, as well as personal fees from AstraZeneca, Inc and STCube Pharmaceuticals. EJK reports grants from National Institutes of Health, Stand Up 2 Cancer, MD Anderson Cancer Center, Elekta, and GE Healthcare, as well as personal fees from RenovoRx and Taylor and Francis. All reported conflicts are outside the submitted work. The authors report no other conflicts of interest in this work., (© 2021 De et al.)

Background: We compared oncologic outcomes of patients who received neoadjuvant chemotherapy (CT) with those of patients who received neoadjuvant chemotherapy plus chemoradiation (CRT) for resectable gastric adenocarcinoma., Methods: We compared oncologic and survival outcomes of patients who received CT or CRT for gastric adenocarcinoma at our institution between July 1995 and July 2018. We analyzed propensity score-matched cohorts based on age, sex, race, tumor histologic characteristics, and clinical stage., Results: We identified 440 patients (mean age 61 ± 12 years, 62% male, 55% white); 345 (78%) received CRT, and 95 (22%) received CT. The propensity score-matched cohorts included 65 patients who received CT and 65 who received CRT. The CRT group had similar frequencies of R1 resection margins to the CT group (7.7% vs. 6.2%, p = 0.75) but significantly higher frequency of pathologic complete response (27.7% vs. 1.5%, p < 0.001). The CRT group had lower pathologic stages (p = 0.002). Median disease-free survival was 50.9 months (95% confidence interval [CI]: 4.7-97.2) in the CT group and 122.1 months (95% CI: 69.0-175.1) in the CRT group (p = 0.07). Median overall survival was 70.7 months (95% CI: 23.9-117.5) in the CT group and 122.1 months (95% CI: 68.7-175.4) in the CRT group (p = 0.21)., Conclusions: Compared with CT, CRT for resectable gastric adenocarcinoma is associated with higher rates of pathologic complete response and subsequent lower final pathologic stage, but survival differences are not significant. Ongoing investigation is necessary to better determine the optimal neoadjuvant therapy and identify patients who receive optimal benefit from CRT., Level of Evidence: III.

Purpose: Localized pancreatic cancer is commonly treated with stereotactic body radiation therapy (SBRT), which often requires the placement of fiducial markers. We compared the clinical outcomes of patients with and without fiducial markers., Methods and Materials: We retrospectively collected data on patients with pancreatic cancer treated with neoadjuvant SBRT at a single institution. Patients were divided into 2 groups based on the placement of a fiducial marker. Local recurrence was the primary outcome. Time to event endpoints were analyzed using COX regression., Results: We included 96 patients with unresectable pancreatic cancer: 46 patients (47.9%) did not have a fiducial marker, and 50 patients (52.1%) had a fiducial placed. Patients in the fiducial group were older and had more locally advanced pancreatic cancer compared with those who did not have a fiducial placed. Most patients in both groups (92.7%) received chemotherapy before SBRT treatment. SBRT was delivered to a median of 36 Gy over 5 fractions in the no-fiducial group, and 38 Gy over 5 fractions in the fiducial group. At a median follow-up of 20 months, local recurrence was similar irrespective of fiducial placement (adjusted hazard ratio [aHR] 0.6, 95% CI 0.3-1.3, P = .59). Furthermore, no difference in overall survival was noted between the 2 groups (aHR 0.8, 95% CI 0.3-1.9, P = .65). In patients who eventually underwent surgery post-SBRT, no difference in surgical margins ( P = .40) or lymphovascular invasion ( P = .76) was noted between the 2 groups. No patient developed acute pancreatitis after fiducial placement., Conclusions: Our data suggest that the use of fiducial markers does not negatively affect clinical outcomes in patients with localized pancreatic cancer. Prospective confirmation of our results is still needed., (© 2020 The Authors.)

Purpose: Recent trends in payer and patient preferences increasingly incentivize time-efficient (≤2-week treatment time) prostate cancer treatments., Methods and Materials: National Medicare claims from January 1, 2011, through December 31, 2014, were analyzed to identify newly diagnosed prostate cancers. Three "radical treatment" cohorts were identified (prostatectomy, brachytherapy, and stereotactic body radiation therapy [SBRT]) and matched to an active surveillance (AS) cohort by using inverse probability treatment weighting via propensity score. Total costs at 1 year after biopsy were calculated for each cohort, and treatment-specific costs were estimated by subtracting total 1-year costs in each radical treatment group from those in the AS group., Results: Mean 1-year adjusted costs were highest among patients receiving SBRT ($26,895), lower for prostatectomy ($23,632), and lowest for brachytherapy ($19,980), whereas those for AS were $9687. Costs of radical modalities varied significantly by region, with the Mid-Atlantic and New England regions having the highest cost ranges (>$10,000) and the West South Central and Mountain regions the lowest range in costs (<$2000). Quantification of toxic effects showed that prostatectomy was associated with higher genitourinary incontinence (hazard ratio [HR] = 10.8 compared with AS) and sexual dysfunction (HR = 3.5), whereas the radiation modalities were associated with higher genitourinary irritation/bleeding (brachytherapy HR = 1.7; SBRT HR = 1.5) and gastrointestinal ulcer/stricture/fistula (brachytherapy HR = 2.7; SBRT HR = 3.0). Overall mean toxicity costs were highest among patients treated with prostatectomy ($3500) followed by brachytherapy ($1847), SBRT ($1327), and AS ($1303)., Conclusions: Time-efficient treatment techniques exhibit substantial variability in toxicity and costs. Furthermore, geographic location substantially influenced treatment costs., (Copyright © 2020 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: The role of neoadjuvant short-course radiation therapy (SCRT) in treating rectal adenocarcinoma is a topic of ongoing debate. Growing interest in total neoadjuvant therapy has spurred discussion on the optimal sequence of preoperative SCRT and chemotherapy., Patients and Methods: All patients receiving SCRT (5 Gy × 5 fractions) were identified. Details about preoperative treatments, radiation toxicities, and postoperative complications were collected. Patients were divided into 2 groups: those who underwent surgery within 14 days of completing SCRT and those with a longer delay. Outcomes compared included extent of pathologic response, margin-negative resection rate, acute radiation toxicities, and postoperative complications., Results: Fifty-seven patients with locally advanced or metastatic rectal cancer received SCRT between 2008 and 2018. Thirty-nine of 57 patients underwent definitive pelvic surgery with total mesorectal excision. There were no significant differences in tumor downstaging, radial margin status, or percent tumor viability between patients with immediate surgery versus delayed surgery. The delay group had higher rates of nodal downstaging (64.7% vs. 18.2%; P = .003). There were no differences in total or grade 3+ gastrointestinal radiation toxicity, postoperative complications, reoperation, readmission, and mortality between the 2 groups., Conclusions: Though not yet common in the United States, SCRT has compared favorably with long course chemoradiation in multiple trials. Moreover, it is associated with greater efficiency and less disruption to chemotherapy. Our data show similar response and toxicity outcomes between the immediate and delay groups, suggesting SCRT is well-tolerated regardless of treatment sequence. Recently completed prospective trials may reveal the optimal preoperative treatment sequence., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The effect of surgeon factors on patient-reported quality-of-life outcomes after breast-conserving therapy (BCT) is unknown and may help patients make informed care decisions., Methods: We performed a survey study of women aged ≥ 67 years with non-metastatic breast cancer diagnosed in 2009 and treated with guideline-concordant BCT, to determine the association of surgeon factors with patient-reported outcomes. The treating surgeon was identified using Medicare claims, and surgeon factors were identified via the American Medical Association Physician Masterfile. The primary outcome was patient-reported cosmetic satisfaction measured by the Cancer Surveillance and Outcomes Research Team (CanSORT) Satisfaction with Breast Cosmetic Outcome instrument, while secondary outcomes included BREAST-Q subdomains. All patient, treatment, and surgeon covariables were included in a saturated multivariable linear regression model with backward elimination applied until remaining variables were p < 0.1., Results: Of 1650 women randomly selected to receive the questionnaire, 489 responded, of whom 289 underwent BCT. Median age at diagnosis was 72 years and the time from diagnosis to survey was 6 years. The mean adjusted CanSORT score was higher for patients treated by surgical oncologists than patients treated by non-surgical oncologists (4.01 [95% confidence interval [CI] 3.65-4.38] vs. 3.53 [95% CI 3.28-3.77], p = 0.006). Similarly, mean adjusted BREAST-Q Physical Well-Being (91.97 [95% CI 86.13-97.80] vs. 83.04 [95% CI 80.85-85.22], p = 0.006) and Adverse Radiation Effects (95.28 [95% CI 91.25-99.31] vs. 88.90 [95% CI 86.23-91.57], p = 0.004) scores were better among patients treated by surgical oncologists., Conclusions: Specialized surgical oncology training is associated with improved long-term patient-reported outcomes. These findings underscore the value of specialized training and may be useful to patients choosing their care team.

Purpose: Partial nephrectomy is the preferred definitive treatment for early stage kidney cancer, with tumor ablative techniques or active surveillance reserved for patients not undergoing surgery. Stereotactic body radiation therapy (SBRT) has emerged as a potential noninvasive alternative for patients with early stage kidney cancer not amenable to surgery, with early reports suggesting excellent rates of local control and limited toxicity., Methods and Materials: The national cancer database from 2004 to 2014 was queried for patients who received a diagnosis of T1N0M0 kidney cancer. Treatments were categorized as surgery (partial or total nephrectomy), tumor ablation (cryoablation or thermal ablation), SBRT (radiation therapy in 5 fractions or less to a total biological effective dose [BED 10 ] of 72 or more), or observation. A propensity score was generated by multinomial logistic regression. A Cox proportional hazards model was fit to determine association between overall survival and treatment group with propensity score adjustments for patient, demographic, and treatment characteristics., Results: A total of 165,298 received surgery, 17,196 underwent tumor ablation, 104 underwent SBRT, and 18,241 were observed. Median follow-up was 51 months. On multivariable analysis, surgery, tumor ablation, and SBRT were associated with a decreased risk of death compared with observation, with hazard ratios of 0.25 (95% confidence interval, 0.24-0.26, P < .001), 0.36 (0.35-0.38, P < .001), and 0.56 (0.39-0.79, P < .001), respectively. When stratifying by BED 10 and compared with observation, hazard ratio for risk of death for patients treated with SBRT to a BED 10 ≥100 (n = 62) and a BED 10 <100 (n = 42) was 0.34 (0.19-0.60, P < .001) and 0.90 (0.58-1.4, P = .64), respectively., Conclusions: In this population-based cohort, patients undergoing high-dose SBRT (BED 10 ≥100) for early stage kidney cancer demonstrated longer survival compared with patients undergoing observation. This may be a promising noninvasive treatment option for nonsurgical candidates with prospective efficacy and safety assessments meriting study in future clinical trials., (© 2020 The Authors.)

Introduction: Pelvic reirradiation (re-RT) presents challenges due to concerns for late toxicity to tissues-at-risk including pelvic bone marrow (PBM). We routinely utilize a hyperfractionated, accelerated re-RT for recurrent rectal or anal cancer in the setting of prior radiation. We hypothesized that proton beam radiation (PBR) is uniquely suited to limit doses to pelvic non-target tissues better than photon-based approaches., Materials and Methods: All patients who received hyperfractionated, accelerated PBR re-RT to the pelvis from 2007 to 2017 were identified. Re-RT was delivered twice daily with a 6 h minimum interfraction interval at 1.5 Gray Relative Biological Effectiveness (Gy(RBE)) per fraction to a total dose of 39-45 Gy(RBE). Concurrent chemotherapy was given to all patients. Comparison photon plans were generated for dosimetric analysis. Dosimetric parameters compared using a matched-pair analysis and the Wilcoxon signed-rank test. Survival analysis was performed Kaplan Meier curves., Results: Fifteen patients were identified, with a median prior pelvic RT dose of 50.4 Gy (range 25-80 Gy). Median time between the initial RT and PBRT re-RT was 4.7 years (range 1.0-36.1 years). In comparison to corresponding photon re-RT plans, PBR re-RT plans had lower mean PBM dose, and lower volume of PBM getting 5 Gy, 10 Gy, 20 Gy, and 30 Gy (p < 0.001, p < 0.001, p < 0.001, and p = 0.033, respectively).With median 13.9 months follow-up after PBR re-RT, five patients had developed local recurrences, and four patients had developed distant metastases. One-year overall survival following PBR re-RT was 67.5% and one-year progression free survival was 58.7%. No patients developed acute or late Grade 4 toxicity., Conclusion: PBR re-RT affords improved sparing of PBM compared with photon-based re-RT. Clinically, PBR re-RT is well-tolerated. However, given modest control rates with definitive re-RT without subsequent surgical resection, a multidisciplinary approach should be favored in this setting when feasible., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Purpose: To examine whether the implementation of Affordable Care Act (ACA) reduced the financial burden associated with cancer care among non-elderly cancer survivors., Methods: Using data from the MEPS-Experiences with Cancer Survivorship Survey, we examined whether there was a difference in financial burden associated with cancer care between 2011 (pre-ACA) and 2016 (post-ACA). Two aspects of financial burden were considered: (1) self-reported financial burden, whether having financial difficulties associated with cancer care and (2) high-burden spending, whether total out-of-pocket (OOP) spending incurred in excess of 10% or 20% of family income. Generalized linear regression models were estimated to adjust the OOP expenditures (reported in 2016 US dollar)., Results: Our sample included adults aged 18-64 with a confirmed diagnosis of any cancer in 2011 (n = 655) and in 2016 (n = 490). There was no apparent difference in the prevalence of cancer survivors reporting any financial hardship or being with high-burden spending between 2011 and 2016. The mean OOP decreased by $268 (95% CI, - 384 to - 152) after the ACA. However, we found that the mean premium payments increased by $421 (95% CI, 149 to 692) in the same period., Conclusions: The ACA was associated with reduced OOP for health services but increased premium contributions, resulting in no significant impact on perceived financial burden among non-elderly cancer survivors., Implications for Cancer Survivors: The financial hardship of cancer survivorship points to the need for the development of provisions that help cancer patients reduce both perceived and materialized burden of cancer care under ongoing health reform.

Objective: To assess treatment patterns, outcomes, and costs for women with low-(LIR) and high-intermediate risk endometrial cancer (HIR) who are treated with and without adjuvant radiotherapy., Methods: All patients with stage I endometrioid endometrial cancer who underwent surgery from 2000 to 2011 were identified from the SEER-Medicare database. LIR was defined as G1-2 tumors with <50% myometrial invasion or G3 with no invasion. HIR was defined as G1-2 tumors with ≥50% or G3 with <50% invasion. Patients were categorized according to whether they received adjuvant radiotherapy (vaginal brachytherapy [VBT], external beam radiotherapy [EBRT], or both) or no radiotherapy. Outcomes were analyzed and compared (primary outcome was overall survival)., Results: 10,842 patients met inclusion criteria. In the LIR group (n = 7609), there was no difference in 10-year overall survival between patients who received radiotherapy and those who did not (67% vs 65%, adjusted HR 0.95, 95% CI 0.81-1.11). In the HIR group (n = 3233), patients who underwent radiotherapy had a significant increase in survival (60% vs 47%, aHR 0.75, 95% CI 0.67-0.85). Radiotherapy was associated with increased costs compared to surgery alone ($26,585 vs $16,712, p < .001). Costs for patients receiving VBT, EBRT, and concurrent VBT/EBRT were $24,044, $27,512, and $31,564, respectively (p < .001). Radiotherapy was associated with an increased risk of gastrointestinal (7 vs 4%), genitourinary (2 vs 1%), and hematologic (16 vs 12%) complications (p < .001)., Conclusions: Radiotherapy was associated with improved survival in women with HIR, but not in LIR. It also had increased costs and a higher morbidity risk. Consideration of observation without radiotherapy in LIR may be reasonable., (Copyright © 2018. Published by Elsevier Inc.)

First-order radiomic features, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), are associated with disease progression in early-stage classical Hodgkin lymphoma (HL). We hypothesized that a model incorporating first- and second-order radiomic features would more accurately predict outcome than MTV or TLG alone. We assessed whether radiomic features extracted from baseline PET scans predicted relapsed or refractory disease status in a cohort of 251 patients with stage I-II HL who were managed at a tertiary cancer center. Models were developed and tested using a machine-learning algorithm. Features extracted from mediastinal sites were highly predictive of primary refractory disease. A model incorporating 5 of the most predictive features had an area under the curve (AUC) of 95.2% and total error rate of 1.8%. By comparison, the AUC was 78% for both MTV and TLG and was 65% for maximum standardize uptake value (SUV max ). Furthermore, among the patients with refractory mediastinal disease, our model distinguished those who were successfully salvaged from those who ultimately died of HL. We conclude that our PET radiomic model may improve upfront stratification of early-stage HL patients with mediastinal disease and thus contribute to risk-adapted, individualized management.

Dose-adjusted rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-R-EPOCH) has produced good outcomes in primary mediastinal B-cell lymphoma (PMBCL), but predictors of resistance to this treatment are unclear. We investigated whether [ 18 F]fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) findings could identify patients with PMBCL who would not respond completely to DA-R-EPOCH. We performed a retrospective analysis of 65 patients with newly diagnosed stage I to IV PMBCL treated at 2 tertiary cancer centers who had PET-CT scans available before and after frontline therapy with DA-R-EPOCH. Pretreatment variables assessed included metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Optimal cutoff points for progression-free survival (PFS) were determined by a machine learning approach. Univariate and multivariable models were constructed to assess associations between radiographic variables and PFS. At a median follow-up of 36.6 months (95% confidence interval, 28.1-45.1), 2-year PFS and overall survival rates for the 65 patients were 81.4% and 98.4%, respectively. Machine learning-derived thresholds for baseline MTV and TLG were associated with inferior PFS (elevated MTV: hazard ratio [HR], 11.5; P = .019; elevated TLG: HR, 8.99; P = .005); other pretreatment clinical factors, including International Prognostic Index and bulky (>10 cm) disease, were not. On multivariable analysis, only TLG retained statistical significance ( P = .049). Univariate analysis of posttreatment variables revealed that residual CT tumor volume, maximum standardized uptake value, and Deauville score were associated with PFS; a Deauville score of 5 remained significant on multivariable analysis ( P = .006). A model combining baseline TLG and end-of-therapy Deauville score identified patients at increased risk of progression., (© 2018 by The American Society of Hematology.)

Purpose: We identified the frequency of racial disparities in guideline-concordant cancer care for select common disease sites in the United States and the impact of guideline concordance on mortality disparities., Methods and Materials: Using Surveillance, Epidemiology, and End Results Medicare data, we evaluated patients age >65 years of black or non-Hispanic white race who were diagnosed with stage III breast (n = 3607), stage I (n = 14,605) or III (n = 15,609) non-small cell lung, or stage III prostate (n = 3548) cancer between 2006 and 2011. Chemotherapy, surgery, and radiation therapy (RT) treatments were identified using claims data. Pearson χ 2 was used to test the associations between race and guideline concordance on the basis of National Comprehensive Cancer Network curative treatment guidelines. Mortality risks were modeled using Cox proportional hazards., Results: Black patients were less likely to receive guideline-concordant curative treatment than non-Hispanic white patients for stage III breast cancer postmastectomy RT (53% black, 61% white; P  = .0014), stage I non-small cell lung cancer stereotactic radiation or surgery (61% black, 75% white; P  < .0001), stage III non-small cell lung cancer chemotherapy in addition to RT or surgery (36% black, 41% white; P  = .0001), and stage III prostate cancer RT or prostatectomy (82% black, 95% white; P  < .0001). Disparities in guideline concordance impacted racial mortality disparities. Specifically, hazard ratios that demonstrated elevated all-cause mortality risks in black patients were lowered (and more closely approached hazard ratio of 1.00) after adjusting for guideline concordance. A similar impact for cause-specific mortality was observed., Conclusions: Racial disparities in the receipt of curative cancer therapy impacted racial mortality disparities across multiple cancer sites. Benchmarking adherence to guideline-concordant care could represent an opportunity to stimulate improvements in disparities in cancer treatment and survival.

Purpose: We identified lung dosimetric constraints to assist in predicting the radiation pneumonitis (RP) risk in patients with mediastinal lymphoma and then identified the clinical prognostic factors that were associated with the achievement of key dosimetric constraints., Methods and Materials: In 190 patients who received mediastinal intensity modulated radiation therapy, we used univariate χ 2 and multivariate logistic models to identify the predictors of RP and achievement of lung dose-volume histogram (DVH) constraints and build a predictive nomogram for RP., Results: An increased risk of RP was strongly associated with mean lung dose (MLD) > 13.5 Gy (odds ratio [OR]: 8.13; 95% confidence interval [CI], 3.01-21.93; P  < .001) and the percent of lung volume receiving ≥5 Gy (V5) > 55% (OR: 7.01; 95% CI, 2.94-16.72; P  < .001). Therefore, patients had low RP risk (8%) if both MLD ≤13.5 and V5 ≤55 constraints were achieved, moderate risk (24%) if only MLD was achieved, and the highest risk (48%) if MLD was not achieved. Deep-inspiration breath-hold (DIBH) technique during treatment strongly prognosticated achieving MLD and V5 DVH constraints (OR,3.88; 95% CI, 1.84-8.19; P  < .001). Specifically, 86% of patients who were treated with DIBH versus 63% without DIBH achieved DVH constraints ( P  < .001). This translated into a "number needed to treat" with DIBH of 4 patients to enable 1 additional patient to achieve both constraints. In comparison, the clinical characteristics were marginal prognosticators: DVH constraints were more likely achieved in nonbulky disease (OR: 3.01; 95% CI, 0.89-4.53; P  = .09) and patients who had not previously received salvage chemotherapy (OR, 2.44; 95% CI, 0.98-6.11; P  = .06). Nomogram-predicted risks of RP ranged from 4% to 60% on the basis of MLD and V5, total radiation dose, and use of salvage chemotherapy., Conclusions: Achieving mean lung and V5 DVH constraints is critical to reduce RP risk in patients with lymphoma who receive mediastinal intensity modulated radiation therapy. The use of the DIBH technique is a promising risk-modifying treatment approach in patients with mediastinal lymphoma and especially in patients with a history of nonmodifiable risk factors for RP such as bulky disease and salvage chemotherapy.

Aims: Non-fluoroscopic catheter ablation is becoming routine. In experienced centres, fluoroscopy is rarely required. The use of a traditional catheterization lab (cath lab) may no longer be necessary. We began performing catheter ablations at a paediatric centre outside the traditional cardiac cath lab in 2013. The purpose of this study was to compare procedural features of paediatric catheter ablation performed outside the cath lab to those performed within a cath lab., Methods and Results: We prospectively looked at patients presenting to the paediatric centre with supraventricular tachycardia (SVT) undergoing catheter ablation outside the cath lab in a standard operating room (OR group). We compared retrospectively to a control group matched for age, type, and location of arrhythmia who had ablations in a traditional cath lab (CL group). Catheter visualization was exclusively by electro-anatomic mapping. Fifty-nine patients with SVT underwent catheter ablation in the OR from October 2013 to December 2015. Thirty-three patients had accessory pathways, 29 were manifest, and 13 of those were left sided. Twenty-six had atrioventricular nodal re-entrant tachycardia. Transseptal puncture with transoesophageal echocardiography guidance was used for 10 left-sided pathways, whereas the other 3 had patent foramen ovales. Procedure time did not differ significantly between groups (OR group mean 131 min, range 57-408; CL group mean 152 min, range 68-376; P = 0.12). Acute success was similar in both groups [OR group: 58/59 (98.3%) and CL group: 57/59 (96.6%)]. There were no major complications in either group. There was no fluoroscopy used in either group., Conclusion: Although performing paediatric catheter ablations outside the traditional cath lab is early in our experience, we produced similar outcomes and results without encountering procedural difficulties of performing ablations in a non-conventional setting. Larger multi-centred trials will be essential to determine the feasibility of this practice., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Purpose: Primary cutaneous anaplastic large cell lymphoma (pcALCL) is conventionally treated with radiation therapy (RT) doses ≥30 GGy, but effectiveness of lower doses is unclear. We compared responses after a range of RT doses for pcALCL., Methods and Materials: From 1999 through 2015, 45 lesions in 21 patients met clinicopathologic pcALCL diagnostic criteria and were treated with RT (<20 Gy, 20-29 Gy, or ≥30 Gy dose). Complete clinical (CR) and partial responses (PR) were compared by dose using Fisher exact test. Progression-free and overall survivals were calculated using the Kaplan-Meier method., Results: Forty-two percent of lesions were treated with <20 Gy, 22% with 20 to 29 Gy, and 35% with ≥30 Gy. Within 12 weeks, 100% responded, with 67% CR and 33% PR; by last follow-up, 87% achieved CR and 13% PR (no difference by RT dose; P = .84). Three-year freedom from local relapse was 100%, 86%, and 100% with <20 Gy, 20 to 29 Gy, and ≥30 Gy, respectively ( P = .28). Many patients ultimately demonstrated other cutaneous or systemic relapse, with 55% 3-year and 29% 10-year progression-free survival. Overall survival at 10 years was 59%, with 2 deaths from complications of disease., Conclusions: Low-dose RT offered excellent local control in the setting of the indolent, chronic course of pcALCL in this patient cohort.

Intrathecal chemotherapy with methotrexate, a folate antagonist, is widely used to treat central nervous system malignancies. The mechanisms underlying methotrexate-induced neurotoxicity are unclear but may be related to increased homocysteine levels. Intrathecal methotrexate-induced myelopathy mimicking subacute combined degeneration, with normal B12 levels, has been documented. We examined treatment and magnetic resonance imaging (MRI) characteristics of 13 patients with leukemia who received intrathecal methotrexate and developed urinary and bowel incontinence, ascending motor weakness, and sensory loss with dorsal column hyperintensity on MRI between 2000 and 2016. Cerebrospinal fluid evaluation was negative for leukemia in all patients and positive for elevated protein in 12 patients. Seven of eight patients with available data had reduced serum folate, increased serum homocysteine, or both, implicating methotrexate as the cause of neurotoxicity. Autopsy of one patient revealed loss of myelinated axons in the posterior columns. These findings suggest that methotrexate neurotoxicity may be mediated by folate antagonism. Awareness and a high index of suspicion of these characteristic clinical and radiographic features in patients who develop myelopathy after intrathecal methotrexate may help to avoid additional neurotoxic therapy in such patients., (© 2016 Wiley Periodicals, Inc.)

Background: Plasmablastic lymphoma (PBL) is an aggressive variant of diffuse large B-cell lymphoma. We sought to assess the treatment outcomes after combined-modality therapy for early-stage PBL., Materials and Methods: We retrospectively reviewed the outcomes of 10 consecutive patients diagnosed with stage I-II PBL from February 2001 to December 2013 at a single institution. The baseline clinical characteristics, treatment modalities, overall outcomes, and treatment-related toxicity were assessed., Results: The median age at diagnosis was 50.5 years. All patients had extranodal disease; 2 were positive for human immunodeficiency virus. Seven patients received hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone)-based chemotherapy, 2 received CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), and 1 received dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin). Radiotherapy (RT) was administered after a complete response to chemotherapy in 7 patients and a partial response in 1 patient. At a median follow-up period of 42 months, the estimated 2-year progression-free and overall survival rates were 90% and 100%, respectively., Conclusion: PBL can be successfully treated with aggressive chemotherapy followed by RT. The treatment was well tolerated and can result in long-term survival for patients with limited-stage disease., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Patients with heart failure (HF) and preserved ejection fraction (EF) have been shown to have high mortality rates, comparable to those with reduced EF. Thus, long-term survivors of HF, regardless of ejection fraction, are a select group. Little is known about disease-related quality of life (QOL) and health status in these patients., Hypothesis: Preserved EF in patients with heart failure independently predicts long-term survival, health related quality of life (QOL), or functional status., Methods: The study followed a cohort of 413 patients consecutively hospitalized for HF between March 1996 and September 1998. In July 2005, information was collected about their mortality, health related QOL as defined by disease-specific Kansas City Cardiomyopathy Questionnaire (KCCQ) scores, and functional decline as defined by limitations in Activities of Daily Living (ADL) scores., Results: The primary outcomes were mortality, QOL, and functional decline. At follow-up, 8.1 years after enrollment, overall mortality was 76% (314/413). Adjusted for age, gender, renal insufficiency, diabetes mellitus, hypertension, HF, and respiratory disease, those with decreased ejection fraction (EF < 40%) had higher mortality compared with those with preserved ejection fraction (hazard ratio [HR] 1.42; confidence interval [CI] = 1.13, 1.80, p = 0.003). The KCCQ scores, including Clinical Summary Scores and Symptom Limitation Scores, as well as ADL limitations, were not significantly different in the survivors with preserved or decreased EF., Conclusions: Heart failure patients with preserved EF have a modest survival advantage compared with those with decreased EF, but health related QOL scores and functional decline in survivors are similar regardless of systolic function.

Background: Little is known about the impact of chronic kidney disease (CKD) on health-related quality-of-life outcomes after coronary artery bypass grafting (CABG)., Methods: Our objective was to examine the changes in physical function (PF) and mental health (MH) 6 months after CABG in 1055 patients with and without CKD. The primary end points were mean change in score and status of "improved" or "worsened" in both PF and MH subscales of the Medical Outcomes Trust Short Form 36-Item Health Survey from baseline to 6 months after CABG, stratified by CKD stage (0-5)., Results: Absolute PF and MH scores at baseline and at 6 months varied by renal impairment level. Patients with severe CKD (stages 4-5) had a mean (SD) decrease in PF score at 6 months of 3 (3) compared with increases in the rest of the cohort (P<.001). After adjustment for baseline score, 21% of patients with advanced CKD experienced worsened PF scores, compared with 0% of patients with stages 0 to 2 and stage 3 CKD (P<.001). In contrast to PF scores, patients with and without CKD had similar improvements in mean MH scores at 6 months, and patients with stages 4 to 5 CKD had the highest frequency of those with improved MH scores (77%). After adjustment, no patients experienced worsened MH scores., Conclusions: After 6 months, patients with severe CKD who underwent CABG had improvement in MH but not improvement in PF and may have had worsened PF compared with those without severe CKD. Comparable evidence regarding quality-of-life outcomes in the absence of CABG is needed to more fully inform decision making regarding patients with severe CKD and coronary artery disease.

Chronic kidney disease (CKD) occurs commonly in patients with cardiovascular disease. In addition, CKD is a risk factor for the development and progression of cardiovascular disease. In this advisory, we present recommendations for the detection of CKD in patients with cardiovascular disease. CKD can be reliably detected with the combined use of the Modification of Diet in Renal Disease equation to estimate glomerular filtration rate and a sensitive test to detect microalbuminuria. All patients with cardiovascular disease should be screened for evidence of kidney disease with these two determinations.

Background: For women with ductal carcinoma in situ (DCIS), radiation therapy after conservative surgery lowers the risk of recurrence. However, emerging evidence suggests that radiation therapy confers only a marginal absolute benefit for older women with DCIS. In a cohort of older women with DCIS, we sought to determine whether radiation therapy was associated with a clinically significant benefit., Methods: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database from January 1, 1992, through December 31, 1999, we identified 3409 women aged 66 years or older treated with conservative surgery for DCIS. A proportional hazards model tested whether radiation therapy was associated with a lower risk of a combined outcome, defined as a subsequent ipsilateral in situ or invasive breast cancer reported by SEER and/or a subsequent mastectomy reported by Medicare claims. The 5-year event risk was determined for patients without and with high-risk features, which were defined as at least one of the following: age 66-69 years, tumor larger than 2.5 cm, comedo histology, and/or high grade. All statistical tests were two-sided., Results: Radiation therapy was associated with a lower risk for each component of the combined outcome (hazard ratio = 0.32, 95% confidence interval [CI] = 0.24 to 0.44). For high-risk patients, the 5-year event risk was 13.6% without radiation therapy versus 3.8% with radiation therapy (difference = 9.8%, 95% CI = 6.5 to 13.2; P<.001). For low-risk patients, the 5-year event risk was 8.2% without radiation therapy versus 1.0% with radiation therapy (difference = 7.2%, 95% CI = 3.6 to 10.9; P<.001). Among healthy women aged 66-79 years, the number needed to treat with radiation therapy to prevent one event in 5 years was 11 for high-risk patients and 15-16 for low-risk patients., Conclusion: For older women with DCIS, radiation therapy appears to confer a substantial benefit that remains meaningful even among low-risk patients.

Chronic kidney disease (CKD) occurs commonly in patients with cardiovascular disease. In addition, CKD is a risk factor for the development and progression of cardiovascular disease. In this advisory, we present recommendations for the detection of CKD in patients with cardiovascular disease. CKD can be reliably detected with the combined use of the Modification of Diet in Renal Disease equation to estimate glomerular filtration rate and a sensitive test to detect microalbuminuria. All patients with cardiovascular disease should be screened for evidence of kidney disease with these two determinations.

Purpose: In ductal carcinoma in situ (DCIS) of the breast, conservative surgery plus radiotherapy (CS+RT) decreases risk of recurrence compared with CS alone. Although nearly one third of patients are reported as treated with CS alone, it is unclear whether this potentially "undertreated" group represents high- or low-risk patients. We evaluated national patterns of DCIS treatment from 1996 to 2001 by patient risk profile., Methods and Materials: In a retrospective cohort of DCIS patients from the Surveillance, Epidemiology, and End Results data, patients were risk stratified on the basis of age at diagnosis, tumor grade, tumor size, and comedo histology. Treatment included CS alone, CS+RT, or mastectomy. Patients were followed for the development of ipsilateral invasive or in situ event., Results: Of 14,202 patients, 19% were low-risk, 46% moderate-risk, and 35% high-risk. A total of 28% received CS alone, 40% CS+RT, and 31% mastectomy. Overall, only 17% of high-risk patients but 44% of low-risk patients received CS alone (p < 0.001). In multivariable analysis, older age, smaller tumor size, and treatment in San Francisco/Los Angeles predicted treatment with CS alone (p < 0.01). Yet despite the tendency to receive CS alone, patients in San Francisco/Los Angeles did not experience an increased risk of ipsilateral event (hazard ratio = 0.79; 95% confidence interval, 0.55-1.12)., Conclusion: Patient risk profiles rationally affect treatment choice in DCIS patients, and the vast majority of high-risk patients do not receive CS alone. Additional follow up is needed to determine whether geographic variation in care influences long-term outcomes.

Background: Renal dysfunction predicts increased mortality in cardiovascular patients, but the best renal estimator for quantifying risks is uncertain. We compared admission serum urea nitrogen (SUN) level, creatinine level, Modification of Diet in Renal Disease (MDRD) rate, and Mayo estimated glomerular filtration rate (eGFR) for predicting mortality., Methods: In a retrospective cohort of Medicare patients (aged > or = 65 years) hospitalized for myocardial infarction (n = 44,437) and heart failure (n = 56,652), renal estimators were compared for linearity with 1-year mortality risk, magnitude of risk, and relative importance for predicting risk (percentage variance explained) in proportional hazards models., Results: The SUN level, creatinine level, and Mayo eGFR had linear associations with mortality. These measures predicted steadily increased risk in patients who experienced a myocardial infarction with a SUN level greater than 17 mg/dL (> 6.1 mmol/L), a creatinine level greater than 1.0 mg/dL (> 88.4 micromol/L), and a Mayo eGFR of less than 100 mL/min per 1.73 m2; and in patients who experienced heart failure with a SUN level greater than 16 mg/dL (> 5.7 mmol/L), a creatinine level greater than 1.1 mg/dL (> 97.2 micromol/L), and a Mayo eGFR of 90 mL/min per 1.73 m2 or less. In contrast, the MDRD eGFR had a J-shaped association and failed to identify increased risks in 50.0% of patients who experienced a myocardial infarction (with an MDRD eGFR > 55 mL/min per 1.73 m2) and 60.0% of patients who experienced heart failure (with an MDRD eGFR > 44 mL/min per 1.73 m2). The SUN level and Mayo eGFR had the greatest magnitude of risks. In myocardial infarction and heart failure patients, adjusted mortality increased by 3% and 7%, respectively, per 5-U increase in SUN, and by 3% and 9%, respectively, per 10-U decrease in Mayo eGFR (P<.001), based on models including both renal measures. Of all the measures, SUN had the greatest magnitude of relative importance for predicting mortality., Conclusions: In older cardiovascular patients, SUN- and creatinine-based measures were powerful predictors of postdischarge mortality. Only MDRD eGFR was less adequate in quantifying risks for patients with mild impairment. Novel estimators, such as the Mayo eGFR, may play an important role in outcomes' prognostication for these patients.

Background: Recent clinical trials have questioned the necessity of breast radiation therapy for older women with early breast cancer. However, the effectiveness of radiation therapy for older women in the community setting has not been addressed., Methods: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database from January 1, 1992, through December 31, 1999, to identify 8724 women aged 70 years or older treated with conservative surgery for small, lymph node-negative, estrogen receptor-positive (or unknown receptor status) breast cancer. We used a proportional hazards model to test whether radiation therapy was associated with a lower risk of a combined outcome, defined as a second ipsilateral breast cancer reported by SEER and/or a subsequent mastectomy reported by Medicare claims. All statistical tests were two-sided., Results: Radiation therapy, compared with no radiation therapy, was associated with a lower risk of the combined outcome (hazard ratio = 0.19, 95% confidence interval = 0.14 to 0.28). Radiation therapy was associated with an absolute risk reduction of 4.0 events per 100 women at 5 years (i.e., from 5.1 events without radiation therapy to 1.1 with radiation therapy) and 5.7 events per 100 persons at 8 years (i.e., from 8.0 events without radiation therapy to 2.3 with radiation therapy) (P < .001, log-rank test). Radiation therapy was most likely to benefit those aged 70-79 years without comorbidity (number needed to treat [NNT] to prevent one event = 21 to 22 patients) and was least likely to benefit those aged 80 years or older with moderate to severe comorbidity (NNT = 61 to 125 patients)., Conclusion: For older women with early breast cancer, radiation therapy was associated with a lower risk of a second ipsilateral breast cancer and subsequent mastectomy. Patients aged 70-79 years with minimal comorbidity were the most likely to benefit, and older patients with substantial comorbidity were least likely to benefit.

Objectives: We estimated the prevalence of renal impairment in heart failure (HF) patients and the magnitude of associated mortality risk using a systematic review of published studies., Background: Renal impairment in HF patients is associated with excess mortality, although precise risk estimates are unclear., Methods: A systematic search of MEDLINE (through May 2005) identified 16 studies characterizing the association between renal impairment and mortality in 80,098 hospitalized and non-hospitalized HF patients. All-cause mortality risks associated with any renal impairment (creatinine >1.0 mg/dl, creatinine clearance [CrCl] or estimated glomerular filtration rate [eGFR] <90 ml/min, or cystatin-C >1.03 mg/dl) and moderate to severe impairment (creatinine > or =1.5, CrCl or eGFR <53, or cystatin-C > or =1.56) were estimated using fixed-effects meta-analysis., Results: A total of 63% of patients had any renal impairment, and 29% had moderate to severe impairment. After follow-up > or =1 year, 38% of patients with any renal impairment and 51% with moderate to severe impairment died versus 24% without impairment. Adjusted all-cause mortality was increased for patients with any impairment (hazard ratio [HR] = 1.56; 95% confidence interval [CI] 1.53 to 1.60, p < 0.001) and moderate to severe impairment (HR = 2.31; 95% CI 2.18 to 2.44, p < 0.001). Mortality worsened incrementally across the range of renal function, with 15% (95% CI 14% to 17%) increased risk for every 0.5 mg/dl increase in creatinine and 7% (95% CI 4% to 10%) increased risk for every 10 ml/min decrease in eGFR., Conclusions: Renal impairment is common among HF patients and confers excess mortality. Renal function should be considered in risk stratification and evaluation of therapeutic strategies for HF patients.

Little is known about the extent to which patients are aware of nationally-recommended cholesterol and lipid subfraction targets. The authors interviewed 738 patients hospitalized with coronary artery disease to assess their knowledge of their low-density lipoprotein, high-density lipoprotein, and total cholesterol levels as well as corresponding national targets. Only 8%, 8%, and 43% of patients could recall their low-density lipoprotein, high-density lipoprotein, and total cholesterol values, respectively. Only 5%, 2%, and 50% could correctly name targets for these values. Knowledge of cholesterol targets was particularly poor among women, nonwhites, and patients without any college education. Patients with multiple cardiac risk factors and patients with a previous history of cardiovascular disease were no more knowledgeable about their cholesterol targets than those without these conditions. These findings suggest that current cholesterol education efforts appear inadequate, particularly for women, nonwhites, and patients without any college education.

Background: Recent reports have suggested that anemia is associated with adverse outcomes in patients with heart failure (HF), but were unable to adjust for a broad range of comorbid conditions. As a result, whether anemia is a truly independent predictor of risk or a marker of comorbid illness in these patients is unknown., Methods: We analyzed medical records from the Centers for Medicare & Medicaid Services' National Heart Care Project, a national sample of 50,405 patients 65 years and older admitted to acute care hospitals with a principal discharge diagnosis of HF between April 1, 1998, and March 31, 1999, or between July 1, 2000, and June 30, 2001. Multivariable logistic regression analyses were conducted to test whether hematocrit level was an independent predictor of all-cause mortality and HF-related readmission at 1 year., Results: In unadjusted analysis, lower hematocrit levels were associated with increased 1-year mortality and readmission for HF. Compared with patients with a hematocrit greater than 40% to 44%, those with a hematocrit of 24% or less had a 51% higher risk of death (relative risk [RR], 1.51; 95% confidence interval [CI], 1.35-1.68; P<.001) and a 17% higher risk of HF-related readmission (RR, 1.17; 95% CI, 1.01-1.34; P = .04). However, after adjustment for multiple comorbidities and other clinical factors, the association between lower hematocrit levels and increased 1-year mortality was markedly attenuated, even in those patients with the most severe anemia (hematocrit, < or = 24% vs > 40%-44%: RR, 1.02; 95% CI, 0.86-1.19; P = .85). The association between lower hematocrit values and HF-related readmission persisted after multivariable adjustment (hematocrit, < or = 24% vs > 40%-44%: RR, 1.21; 95% CI, 1.04-1.38; P = .01)., Conclusions: Although anemia is an independent predictor of hospital readmission, its relationship with increased mortality in HF patients is largely explained by the severity of comorbid illness. These findings suggest that anemia may be predominantly a marker rather than a mediator of increased mortality risk in older patients with HF.

Purpose: Three classification and prognostic systems exist for primary cutaneous B-cell lymphoma (PCBCL). Whereas the WHO classification defines its categories based on histology, both the European Organisation for Research and Treatment of Cancer classification and the conventional staging system consider skin site. We sought to incorporate both histology and skin site into a single prognostic index designed to predict survival in patients with PCBCL., Methods: The associations between histology, skin site, and survival were determined using adjusted proportional hazards analysis conducted on 926 patients with PCBCL identified in the Surveillance, Epidemiology, and End Results data, spanning 1973 to 2001., Results: Four primary CBCL prognostic index (CBCL-PI) groups were identified. Group IA included indolent histologies involving any skin site. Group IB included diffuse large B-cell histology involving favorable skin sites (head/neck, arm). Group II included diffuse large B-cell histology involving unfavorable skin sites (trunk, legs, disseminated) or immunoblastic large B-cell histology involving favorable skin sites. Group III included immunoblastic large B-cell histology involving unfavorable skin sites. The adjusted mortality hazards ratios were 1.0, 1.3 (95% CI, 0.99 to 1.7), 2.1 (95% CI, 1.6 to 2.7), and 4.5 (95% CI, 2.8 to 7.2) for groups IA/B to III, respectively. The corresponding 5-year relative survivals were 94%, 86%, 60%, and 34%., Conclusion: The CBCL-PI identifies adverse combinations of histology and skin site, helping to reconcile differences in current classification and prognostic systems for PCBCL.

Background: Renal impairment is an emerging prognostic indicator in heart failure (HF) patients. Despite known racial differences in the progression of both HF and renal disease, it is unclear whether the prognosis for renal impairment in HF patients differs by race. We sought to determine in HF patients the 1-year mortality risks associated with elevated creatinine and impaired estimated glomerular filtration rate (eGFR) and to quantify racial differences in mortality., Methods and Results: We retrospectively evaluated the National Heart Care Project nationally representative cohort of 53,640 Medicare patients hospitalized with HF. Among 5669 black patients, mean creatinine was 1.6+/-0.9 mg/dL, and 54% had an eGFR < or =60, compared with creatinine 1.5+/-0.7 mg/dL and 68% eGFR < or =60 in 47,971 white patients. Higher creatinine predicted increased mortality risk, although the magnitude of risk differed by race (interaction P=0.0001). Every increase in creatinine of 0.5 mg/dL was associated with a >10% increased risk in adjusted mortality for blacks, compared with >15% increased risk in whites (interaction P=0.0001), with the most striking racial disparities at the highest levels of renal impairment. Depressed eGFR showed similar racial differences (interaction P=0.0001)., Conclusions: Impaired renal function predicts increased mortality in elderly HF patients, although risks are more pronounced in whites. Distinct morbidity and mortality burdens in black versus white patients underscore the importance of improving patient risk-stratification, defining optimal therapies, and exploring physiological underpinnings of racial differences.

Purpose: To determine the relationship between postmastectomy radiotherapy (PMRT) and mortality in a population-based cohort of women with T1-2 node-positive breast cancer., Patients and Methods: Using data from the Surveillance, Epidemiology, and End Results program, we identified 18,038 women with T1-2 node-positive invasive breast cancer who were treated with mastectomy between 1988 and 1995. The relationship between PMRT and mortality was determined using proportional hazards multivariate modeling and propensity score matched case-control analysis., Results: Median follow-up was 8.1 years. Only 2,648 women (15%) received PMRT. After adjusting for covariates, PMRT use was not associated with mortality (hazard ratio [HR] = 0.96; 95% CI, 0.90 to 1.03). However, the interaction term for PMRT use and number of involved regional lymph nodes was significant (P = .002), suggesting that, above a certain threshold of involved nodes, a mortality benefit from PMRT may exist. Adjusted analysis stratified by number of involved nodes revealed that patients with seven or more involved nodes treated with PMRT experienced a significant reduction in all-cause (HR = 0.84; 95% CI, 0.76 to 0.93) and cause-specific mortality (HR = 0.86; 95% CI, 0.77 to 0.96). Propensity score matched case-control analysis confirmed that PMRT was associated with reduced mortality only in the subset of patients with seven or more involved nodes (HR = 0.81; 95% CI, 0.73 to 0.91 for all-cause mortality; and HR = 0.82; 95% CI, 0.72 to 0.93 for cause-specific mortality)., Conclusion: For women with T1-2 breast cancer, PMRT is associated with a 15% to 20% relative reduction in mortality for patients with seven or more involved regional lymph nodes.

Renal dysfunction is a common complication for patients with heart failure, but its association with clinical outcomes has not been fully characterized. We evaluated the association of glomerular filtration rate (GFR) with heart failure survival and the effect of digoxin on heart failure outcomes across GFR strata. A secondary analysis from the Digitalis Intervention Group trial was conducted of 6800 outpatients with systolic heart failure. Renal function was categorized as estimated GFR (expressed in ml/min per 1.73 m(2)). All-cause mortality (mean, 3 yr) was inversely proportional to GFR (GFR >60, 31% mortality; GFR 30 to 60, 46% mortality; GFR <30, 62% mortality; P < 0.001). Among patients with a GFR <50, lower GFR were associated with greater adjusted mortality risk (GFR <30: hazard ratio [HR], 2.06, 95% confidence interval [CI], 1.69 to 2.51; GFR 30 to 40: HR, 1.42, 95% CI, 1.22 to 1.67; GFR 40 to 50: HR, 1.22, 95% CI, 1.07 to 1.39; GFR 50 to 60: HR, 1.00, referent). In contrast, participants with GFR 60 to 70 had similar risk (HR, 1.00; 95% CI, 0.88 to 1.14) compared with GFR 50 to 60, and those with GFR >70 had a slightly lower mortality hazard (0.89; 95% CI, 0.78 to 1.00). Linear spline analyses confirmed that GFR = 50 was the appropriate risk threshold; above 50, GFR had no association with mortality, whereas below 50, mortality risk increased sharply with declining GFR (spline coefficient, P < 0.0001). Digoxin efficacy did not differ by level of GFR (P = 0.19 for interaction). Renal dysfunction is strongly associated with mortality in stable outpatients with heart failure, notably in patients with estimated GFR <50 ml/min per 1.73 m(2). The effect of digoxin did not differ by level of renal function.

Background: Despite national efforts to improve cholesterol management for patients with coronary artery disease, many patients are not reaching recommended cholesterol target levels. We sought to determine whether a nurse-based educational intervention, designed to educate patients with confirmed coronary artery disease about personal low-density lipoprotein (LDL) cholesterol target levels and encourage partnership with physicians, could increase adherence with National Cholesterol Education Program target levels (LDL cholesterol level < or =100 mg/dL)., Methods: Patients hospitalized with confirmed coronary artery disease were randomized to undergo a nurse-based educational intervention (375 patients) or usual care (381 patients) for a 12-month period after hospitalization. The primary outcome was the proportion of patients at the LDL cholesterol target level 1 year after hospitalization. The secondary outcome was the proportion of patients with accurate knowledge of LDL cholesterol target levels., Results: The groups were similar at baseline in demographic and clinical characteristics, percent at LDL cholesterol target level (43.9% and 41.1%, respectively), and percent with knowledge of LDL cholesterol target levels (both 5%). The proportion of patients at LDL cholesterol target levels at 1 year did not differ between the intervention (70.2%) and usual care group (67.4%, P =.46). At the conclusion of the trial, patient knowledge about LDL cholesterol target level was higher for the intervention group than the usual care group (19.6% and 6.7%, respectively, P =.001), but this was not associated with improved cholesterol management., Conclusions: Our nurse-based educational intervention did not result in a significant increase in the proportion of patients who reached target LDL cholesterol levels 1 year after hospitalization. Although the intervention improved patient knowledge of LDL cholesterol target levels, overall rates of LDL cholesterol knowledge remained low, and it was not associated with improved cholesterol management.

Purpose: To determine the relationship between the WHO and European Organization for Research and Treatment of Cancer (EORTC) pathologic classifications for primary cutaneous B-cell lymphoma (CBCL) and the implication of this relationship on initial treatment., Patients and Methods: Patients with primary CBCL treated with radiotherapy were identified retrospectively. Initial biopsy specimens were reviewed by two dermatopathologists and classified according to the EORTC and WHO systems. Primary outcomes were recurrence-free and overall survival., Results: Thirty-four patients were identified; initial biopsy specimens were adequate for classification in 32 patients. Four different composite histopathologic subtypes of lymphoma were identified: 53% (17 of 32) follicle center cell by EORTC and diffuse large B-cell by WHO (FCC/DLB), 25% (eight of 32) follicle center cell by EORTC and follicular by WHO (FCC/Fol), 13% (four of 32) marginal zone by EORTC and WHO (MZ/MZ), and 9% (three of 32) large B-cell of the leg by EORTC and diffuse large B-cell by WHO (Leg/DLB). Five-year relapse-free survival ranged from 62% to 73% for FCC/DLB, FCC/Fol, and MZ/MZ but was 33% for Leg/DLB (P =.6). Five-year overall survival was 100% for FCC/DLB, FCC/Fol, and MZ/MZ but was 67% for Leg/DLB (P =.07). At 5 years, 21% of all patients had developed extracutaneous disease., Conclusion: Two-thirds of primary cutaneous FCC lymphomas by EORTC criteria satisfy WHO criteria for DLB lymphoma. Unlike DLB lymphoma presenting in nodal or noncutaneous sites, these lesions are associated with an indolent course and may be treated with local radiotherapy alone.

Context: Black patients hospitalized with heart failure reportedly receive poorer quality of care and have worse outcomes than white patients. Because previous studies have been based on selected patient populations treated more than a decade ago, it is unclear if racial differences in quality of care and outcomes currently exist in the United States., Objective: To evaluate differences in quality of care and patient outcomes between black and white Medicare beneficiaries hospitalized with heart failure., Design: Retrospective analysis of medical record data systematically collected for the National Heart Failure Project., Setting and Patients: Nationwide US sample of 29 732 fee-for-service Medicare beneficiaries hospitalized with heart failure in 1998 and 1999., Main Outcome Measures: Prescription of angiotensin-converting enzyme (ACE) inhibitors, measurement of left ventricular ejection fraction (LVEF), readmission within 1 year of discharge, and mortality within 30 days and 1 year of admission., Results: Black patients and white patients had similar crude rates of LVEF assessment (67.8% black vs 66.6% white; P =.29). Among patients classified as ideal for ACE inhibitor use, black patients had higher crude rates of ACE inhibitor use than white patients (81.0% vs 73.8% white; P<.001) but had similar rates of ACE inhibitor or angiotensin receptor blocker (ARB) use (85.7% black vs 82.5% white; P =.08). After multivariable adjustment, black patients had comparable rates of LVEF assessment (risk ratio [RR], 0.99; 95% confidence interval [CI], 0.95-1.03). Black patients remained more likely to be prescribed ACE inhibitors (RR, 1.22; 95% CI, 1.14-1.28) than were white patients in an adjusted analysis, but there were no significant racial differences in the prescription of ACE inhibitors or ARBs (black vs white, RR, 1.03; 95% CI, 0.97-1.07). Black patients had higher rates of readmission within 1 year of discharge (68.2% vs 63.0%; P<.001) but had lower crude 30-day (6.3% vs 10.7%; P<.001) and 1-year (31.5% vs 40.1%; P<.001) mortality rates than white patients. After multivariable adjustment, black patients had a slightly higher rate of readmission than white patients (RR, 1.09; 95% CI, 1.06-1.13) but remained at lower risk of 30-day mortality (RR, 0.78; 95% CI, 0.68-0.91) and 1-year mortality (RR, 0.93; 95% CI, 0.88-0.98)., Conclusions: Black Medicare patients hospitalized with heart failure received comparable quality of care and had slightly higher rates of readmission but had lower mortality rates up to 1 year after hospitalization than did white patients.

Objectives: We evaluated the six-month clinical trajectory of patients hospitalized for heart failure (HF) with preserved ejection fraction (EF), as the natural history of this condition has not been well established. We compared mortality, hospital readmission, and changes in functional status in patients with preserved versus depressed EF., Background: Although the poor prognosis of HF with depressed EF has been extensively documented, there are only limited and conflicting data concerning clinical outcomes for patients with preserved EF., Methods: We prospectively evaluated 413 patients hospitalized for HF to determine whether EF >or=40% was an independent predictor of mortality, readmission, and the combined outcome of functional decline or death., Results: After six months, 13% of patients with preserved EF died, compared with 21% of patients with depressed EF (p = 0.02). However, the rates of functional decline were similar among those with preserved and depressed EF (30% vs. 23%, respectively; p = 0.14). After adjusting for demographic and clinical covariates, preserved EF was associated with a lower risk of death (hazard ratio [HR] 0.49, 95% confidence interval [CI] 0.26 to 0.90; p = 0.02), but there was no difference in the risk of readmission (HR 1.01, 95% CI 0.72 to 1.43; p = 0.96) or the odds of functional decline or death (OR 1.01, 95% CI 0.59 to 1.72; p = 0.97)., Conclusions: Heart failure with preserved EF confers a considerable burden on patients, with the risk of readmission, disability, and symptoms subsequent to hospital discharge, comparable to that of HF patients with depressed EF.

Introduction: Worsening renal function during hospitalization for heart failure, defined as elevation in creatinine during admission, predicts adverse outcomes. Prior studies define worsening renal function using various creatinine elevations, but the relative value of definitions is unknown., Methods and Results: In a prospective cohort of 412 patients hospitalized for heart failure, we compared a spectrum of worsening renal function definitions (absolute creatinine elevations >/=0.1 to >/=0.5 mg/dL and 25% relative elevation from baseline) and associations with 6-month mortality, readmission, and functional decline. Creatinine elevation >/=0.1 mg/dL occurred in 75% of patients, and elevation >/=0.5 mg/dL occurred in 24% of patients. Risk of death rose with higher creatinine elevations (adjusted hazard ratio [HR] = 0.89, 1.19, 1.67, 1.91, and 2.90 for elevations >/=0.1 to >/=0.5 mg/dL). Maximum sensitivity of any definition for predicting mortality was 75% and maximum specificity was 79%. High creatinine elevation was a more important predictor of death than was a single measure of baseline creatinine., Conclusions: Larger creatinine elevations predict highest risk of death, yet even minor changes in renal function are associated with adverse outcomes. The choice of a "best definition" for worsening renal function has implications for the number of patients identified with this risk factor and the magnitude of risk for mortality.

Physiologic studies have suggested that anemia could adversely affect the cardiovascular condition of patients with heart failure. Yet, the prognostic importance of this treatable condition is not well established by epidemiologic studies. We sought to determine the prognostic value of hematocrit level in a cohort of elderly patients hospitalized with heart failure. We studied a consecutive sample of 2281 patients aged 65 years or older who had been admitted with a principal discharge diagnosis of heart failure. Multivariate Cox proportional hazards regression was conducted to test whether hematocrit level was an independent predictor of 1-year mortality and of hospital readmission. The mean (+/- SD) age of the patients was 79 +/- 8 years; 58% (n = 1324) were women. Their median hematocrit was 38% (25th to 75th percentile, 33% to 42%). Lower hematocrits were associated with a higher mortality. After adjusting for demographic and clinical factors, each 1% lower hematocrit was associated with a 2% greater 1-year mortality (P = 0.007). Compared with patients with a hematocrit >42%, those with a hematocrit < or =27% had a 40% greater 1-year mortality (hazard ratio [HR] = 1.40; 95% confidence interval [CI]: 1.02 to 1.92; P = 0.04). This increased risk was similar to that conferred by traditional risk factors, including a left ventricular ejection fraction < or =20% (HR = 1.50; 95% CI: 1.20 to 1.86). Lower hematocrits were also associated with a greater risk of hospital readmission. Anemia is associated with an increased risk of death and rehospitalization in older patients with heart failure. Whether anemia is a direct cause of worse outcomes, or a marker for other causal factors, is not known.

Purpose: The role of HER-2/neu in squamous cell carcinoma (SCC) of the head and neck is not well defined. The purpose of the current study is to measure the frequency of HER-2/neu expression, to demonstrate HER-2/neu gene amplification in the cases found to be positive for protein overexpression, and to investigate the prognostic significance of overexpression and/or amplification in SCC of the head and neck., Experimental Design: A cohort of 77 patients with SCC of the oral cavity or oropharynx, with stage III or IV disease and uniformly treated with surgical resection and postoperative radiation, served as the primary patient population for the study. Of these, 56 patients had adequate follow-up and paraffin-embedded specimens available for analysis. Median follow-up was 6.1 years. Each of the paraffin-embedded specimens were immunohistochemically stained for HER-2/neu expression and graded for intensity of staining by a pathologist. All cases that demonstrated positive staining by immunohistochemistry were analyzed by fluorescence in situ hybridization (FISH) to assess HER-2/neu amplification status., Results: Five-year survival for the 56 evaluable patients was 40%, with 25% experiencing local relapse, 18% regional relapse, and 25% distant relapse. The percentage of tumors staining positive for HER-2/neu by immunohistochemistry was 17%. There was no statistically significant correlation between HER-2/neu and T stage, N stage, tumor grade, survival, or disease-free survival. HER-2/neu expression did correlate with vascular endothelial growth factor expression. FISH analysis revealed four cases that were amplified for HER-2/neu. Of note, of the 4 amplified cases, 2 suffered regional relapse, 1 suffered distant metastasis, and all 4 expired by 5 years of follow-up., Conclusions: This is the first demonstration of HER-2/neu gene amplification by FISH in SCC of the head and neck. FISH validates a previously contested controversial role for HER-2/neu gene overexpression in SCC of the head and neck. The prognostic significance and clinical implications of HER-2/neu expression and amplification in head and neck cancer will require additional studies.

Objectives: We determined the effect of a targeted education and support intervention on the rate of readmission or death and hospital costs in patients with heart failure (HF)., Background: Disease management programs for patients with HF including medical components may reduce readmissions by 40% or more, but the value of an intervention focused on education and support is not known., Methods: We conducted a prospective, randomized trial of a formal education and support intervention on one-year readmission or mortality and costs of care for patients hospitalized with HF., Results: Among the 88 patients (44 intervention and 44 control) in the study, 25 patients (56.8%) in the intervention group and 36 patients (81.8%) in the control group had at least one readmission or died during one-year follow-up (relative risk = 0.69, 95% confidence interval [CI]: 0.52, 0.92; p = 0.01). The intervention was associated with a 39% decrease in the total number of readmissions (intervention group: 49 readmissions; control group: 80 readmissions, p = 0.06). After adjusting for clinical and demographic characteristics, the intervention group had a significantly lower risk of readmission compared with the control group (hazard ratio = 0.56, 95% CI: 0.32, 0.96; p = 0.03) and hospital readmission costs of $7,515 less per patient., Conclusions: A formal education and support intervention substantially reduced adverse clinical outcomes and costs for patients with HF.