International practice patterns of dyslipidemia management in patients with chronic kidney disease under nephrology care: is it time to review guideline recommendations?

BACKGROUND: In contrast to guidelines related to lipid therapy in other areas, 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend conducting a lipid profile upon diagnosis of chronic kidney disease (CKD) and treating all patients older than 50 years without defining a target for lipid levels. We evaluated multinational practice patterns for lipid management in patients with advanced CKD under nephrology care. METHODS: We analyzed lipid-lowering therapy (LLT), LDL- cholesterol (LDL-C) levels, and nephrologist-specified LDL-C goal upper limits in adult patients with eGFR < 60 ml/min from nephrology clinics in Brazil, France, Germany, and the United States (2014-2019). Models were adjusted for CKD stage, country, cardiovascular risk indicators, sex, and age. RESULTS: LLT treatment differed significantly by country, from 51% in Germany to 61% in the US and France (p = 0.002) for statin monotherapy. For ezetimibe with or without statins, the prevalence was 0.3% in Brazil to 9% in France (< 0.001). Compared with patients not taking lipid-lowering therapy, LDL-C was lower among treated patients (p < 0.0001) and differed significantly by country (p < 0.0001). At the patient level, the LDL-C levels and statin prescription did not vary significantly by CKD stage (p = 0.09 LDL-C and p = 0.24 statin use). Between 7-23% of untreated patients in each country had LDL-C ≥ 160 mg/dL. Only 7-17% of nephrologists believed that LDL-C should be < 70 mg/dL. CONCLUSION: There is substantial variation in practice patterns regarding LLT across countries but not across CKD stages. Treated patients appear to benefit from LDL-C lowering, yet a significant proportion of hyperlipidemia patients under nephrologist care are not receiving treatment.

Etelcalcetide Utilization, Dosing Titration, and Chronic Kidney Disease-Mineral and Bone Disease (CKD-MBD) Marker Responses in US Hemodialysis Patients.

RATIONALE & OBJECTIVE: Clinical trial data have demonstrated the efficacy of etelcalcetide for reducing parathyroid hormone (PTH) levels in hemodialysis (HD) patients. We provide a real-world summary of etelcalcetide utilization, dosing, effectiveness, and discontinuation since its US introduction in April 2017. STUDY DESIGN: New-user design within prospective cohort. SETTING & PARTICIPANTS: 2,596 new users of etelcalcetide from April 2017 through August 2019 in a national sample of adult maintenance HD patients in the US Dialysis Outcomes and Practice Patterns Study (DOPPS). PREDICTORS: Baseline PTH, prior cinacalcet use, initial etelcalcetide dose. OUTCOME: Trajectories of etelcalcetide dose, chronic kidney disease-mineral and bone disease (CKD-MBD) medications, and levels of PTH, serum calcium, and phosphorus in the 12 months after etelcalcetide initiation. ANALYTICAL APPROACH: Cumulative incidence methods for etelcalcetide discontinuation and linear generalized estimating equations for trajectory analyses. RESULTS: By August 2019, etelcalcetide prescriptions increased to 6% of HD patients from their first use in April 2017. Starting etelcalcetide dose was 15 mg/wk in 70% of patients and 7.5 mg/wk in 27% of patients; 49% of new users were prescribed cinacalcet in the prior 3 months. Etelcalcetide discontinuation was 9%, 17%, and 27% by 3, 6, and 12 months after initiation. One year after etelcalcetide initiation, mean PTH levels declined by 40%, from 948 to 566 pg/mL, and the proportion of patients with PTH within target (150-599 pg/mL) increased from 33% to 64% overall, from 0 to 60% among patients with baseline PTH ≥ 600 pg/mL, and from 30% to 63% among patients with prior cinacalcet use. The proportion of patients with serum phosphorus > 5.5 mg/dL decreased from 55% to 45%, while the prevalence of albumin-corrected serum calcium < 7.5 mg/dL remained at 1%-2%. There were increases in use of active vitamin D (from 77% to 87%) and calcium-based phosphate binders (from 41% to 50%) in the 12 months after etelcalcetide initiation. LIMITATIONS: Data are unavailable for provider dosing protocols, dose holds, or reasons for discontinuation. CONCLUSIONS: In the 12 months after etelcalcetide initiation, patients had large and sustained reductions in PTH levels. These results support the utility of etelcalcetide as an effective therapy to achieve the KDIGO-recommended guidelines for CKD-MBD markers in HD patients.

Serum Biomarkers of Iron Stores Are Associated with Increased Risk of All-Cause Mortality and Cardiovascular Events in Nondialysis CKD Patients, with or without Anemia.

BACKGROUND: Approximately 30%-45% of patients with nondialysis CKD have iron deficiency. Iron therapy in CKD has focused primarily on supporting erythropoiesis. In patients with or without anemia, there has not been a comprehensive approach to estimating the association between serum biomarkers of iron stores, and mortality and cardiovascular event risks. METHODS: The study included 5145 patients from Brazil, France, the United States, and Germany enrolled in the Chronic Kidney Disease Outcomes and Practice Patterns Study, with first available transferrin saturation (TSAT) and ferritin levels as exposure variables. We used Cox models to estimate hazard ratios (HRs) for all-cause mortality and major adverse cardiovascular events (MACE), with progressive adjustment for potentially confounding variables. We also used linear spline models to further evaluate functional forms of the exposure-outcome associations. RESULTS: Compared with patients with a TSAT of 26%-35%, those with a TSAT ≤15% had the highest adjusted risks for all-cause mortality and MACE. Spline analysis found the lowest risk at TSAT 40% for all-cause mortality and MACE. Risk of all-cause mortality, but not MACE, was also elevated at TSAT ≥46%. Effect estimates were similar after adjustment for hemoglobin. For ferritin, no directional associations were apparent, except for elevated all-cause mortality at ferritin ≥300 ng/ml. CONCLUSIONS: Iron deficiency, as captured by TSAT, is associated with higher risk of all-cause mortality and MACE in patients with nondialysis CKD, with or without anemia. Interventional studies evaluating the effect on clinical outcomes of iron supplementation and therapies for alternative targets are needed to better inform strategies for administering exogenous iron.

Beta-2 microglobulin and all-cause mortality in the era of high-flux hemodialysis: results from the Dialysis Outcomes and Practice Patterns Study.

BACKGROUND: Beta-2 microglobulin (ß2M) accumulates in hemodialysis (HD) patients, but its consequences are controversial, particularly in the current era of high-flux dialyzers. High-flux HD treatment improves ß2M removal, yet ß2M and other middle molecules may still contribute to adverse events. We investigated patient factors associated with serum ß2M, evaluated trends in ß2M levels and in hospitalizations due to dialysis-related amyloidosis (DRA), and estimated the effect of ß2M on mortality. METHODS: We studied European and Japanese participants in the Dialysis Outcomes and Practice Patterns Study. Analysis of DRA-related hospitalizations spanned 1998-2018 (n = 23 976), and analysis of ß2M and mortality in centers routinely measuring ß2M spanned 2011-18 (n = 5332). We evaluated time trends with linear and Poisson regression and mortality with Cox regression. RESULTS: Median ß2M changed nonsignificantly from 2.71 to 2.65 mg/dL during 2011-18 (P = 0.87). Highest ß2M tertile patients (>2.9 mg/dL) had longer dialysis vintage, higher C-reactive protein and lower urine volume than lowest tertile patients (≤2.3 mg/dL). DRA-related hospitalization rates [95% confidence interval (CI)] decreased from 1998 to 2018 from 3.10 (2.55-3.76) to 0.23 (0.13-0.42) per 100 patient-years. Compared with the lowest ß2M tertile, adjusted mortality hazard ratios (95% CI) were 1.16 (0.94-1.43) and 1.38 (1.13-1.69) for the middle and highest tertiles. Mortality risk increased monotonically with ß2M modeled continuously, with no indication of a threshold. CONCLUSIONS: DRA-related hospitalizations decreased over 10-fold from 1998 to 2018. Serum ß2M remains positively associated with mortality, even in the current high-flux HD era.

Serum biomarkers of iron stores are associated with worse physical health-related quality of life in nondialysis-dependent chronic kidney disease patients with or without anemia.

BACKGROUND: Iron deficiency (ID) is a common condition in nondialysis-dependent chronic kidney disease (NDD-CKD) patients that is associated with poorer clinical outcomes. However, the effect of ID on health-related quality of life (HRQoL) in this population is unknown. We analyzed data from a multinational cohort of NDD-CKD Stages 3-5 patients to test the association between transferrin saturation (TSAT) index and ferritin with HRQoL. METHODS: Patients from Brazil (n = 205), France (n = 2015) and the USA (n = 293) in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps, 2013-2019) were included. We evaluated the association of TSAT and ferritin (and functional and absolute ID, defined as TSAT ≤20% and ferritin ≥300 or <50 ng/mL) on pre-specified HRQoL measures, including the 36-item Kidney Disease Quality of Life physical component summary (PCS) and mental component summary (MCS) as the primary outcomes. Models were adjusted for confounders including hemoglobin (Hb). RESULTS: TSAT ≤15% and ferritin <50 ng/mL and ≥300 ng/mL were associated with worse PCS scores, but not with MCS. Patients with composite TSAT ≤20% and ferritin <50 or ≥300 ng/mL had lower functional status and worse PCS scores than those with a TSAT of 20-30% and ferritin 50-299 ng/mL. Patients with a lower TSAT were less likely to perform intense physical activity. Adjustment for Hb only slightly attenuated the observed effects. CONCLUSIONS: Low TSAT levels, as well as both low TSAT with low ferritin and low TSAT with high ferritin, are associated with worse physical HRQoL in NDD-CKD patients, even after accounting for Hb level. Interventional studies of iron therapy on HRQoL among NDD-CKD individuals are needed to confirm these findings.

Associations of Hemoglobin Levels With Health-Related Quality of Life, Physical Activity, and Clinical Outcomes in Persons With Stage 3-5 Nondialysis CKD.

OBJECTIVE: Conflicting findings and knowledge gaps exist regarding links between anemia, physical activity, health-related quality of life (HRQOL), chronic kidney disease (CKD) progression, and mortality in moderate-to-advanced CKD. Using the CKD Outcomes and Practice Patterns Study, we report associations of hemoglobin (Hgb) with HRQOL and physical activity, and associations of Hgb and physical activity with CKD progression and mortality in stage 3-5 nondialysis (ND)-CKD patients. DESIGN AND METHODS: Prospectively collected data were analyzed from 2,121 ND-CKD stage 3-5 patients, aged ≥18 years, at 43 nephrologist-run US and Brazil CKD Outcomes and Practice Patterns Study-participating clinics. Cross-sectional associations were assessed of Hgb levels with HRQOL and physical activity levels (from validated Kidney Disease Quality of Life Instrument and Rapid Assessment of Physical Activity surveys). CKD progression (first of ≥40% estimated glomerular filtration rate [eGFR] decline, eGFR<10 mL/min/1.73 m2, or end-stage kidney disease) and all-cause mortality with Hgb and physical activity levels were also evaluated. Linear, logistic, and Cox regression analyses were adjusted for country, demographics, smoking, eGFR, serum albumin, very high proteinuria, and 13 comorbidities. RESULTS: HRQOL was worse, with severe anemia (Hgb<10 g/dL), but also evident for mild/moderate anemia (Hgb 10-12 g/dL), relative to Hgb>12 g/dL. Odds of being highly physically active were substantially greater at Hgb>10.5 g/dL. Lower Hgb was strongly associated with greater CKD progression and mortality, even after extensive adjustment. Physical inactivity was strongly associated with greater mortality and weakly associated with CKD progression. Possible residual confounding is a limitation. CONCLUSION: This multicenter international study provides real-world observational evidence for greater HRQOL, physical activity, lower CKD progression, and greater survival in ND-CKD patients with Hgb levels >12 g/dL, exceeding current treatment guideline recommendations. These findings help inform future studies aimed at understanding the impact of new anemia therapies and physical activity regimens on improving particular dimensions of ND-CKD patient well-being and clinical outcomes.

Cardiac Dose in Locally Advanced Lung Cancer: Results From a Statewide Consortium.

PURPOSE: The heart has been identified as a potential significant organ at risk in patients with locally advanced non-small cell lung cancer treated with radiation. Practice patterns and radiation dose delivered to the heart in routine practice in academic and community settings are unknown. METHODS AND MATERIALS: Between 2012 and 2017, 746 patients with stage III non-small cell lung cancer were treated with radiation within the statewide Michigan Radiation Oncology Quality Consortium (MROQC). Cardiac radiation dose was characterized, including mean and those exceeding historical or recently proposed Radiation Therapy Oncology Group and NRG Oncology constraints. Sites were surveyed to determine dose constraints used in practice. Patient-, anatomic-, and treatment-related associations with cardiac dose were analyzed using multivariable regression analysis and inverse probability weighting. RESULTS: Thirty-eight percent of patients had a left-sided primary, and 80% had N2 or N3 disease. Median prescription was 60 Gy (interquartile range, 60-66 Gy). Twenty-two percent of patients were prescribed 60 Gy in 2012, which increased to 62% by 2017 (P < .001). Median mean heart dose was 12 Gy (interquartile range, 5-19 Gy). The volume receiving 30 Gy (V30 Gy) exceeded 50% in 5% of patients, and V40 Gy was >35% in 3% of cases. No heart dose constraint was uniformly applied. Intensity modulated radiation therapy (IMRT) usage increased from 33% in 2012 to 86% in 2017 (P < .001) and was significantly associated with more complex cases (larger planning target volume, higher stage, and preexisting cardiac disease). In multivariable regression analysis, IMRT was associated with a lower percent of the heart receiving V30 Gy (absolute reduction = 3.0%; 95% confidence interval, 0.5%-5.4%) and V50 Gy (absolute reduction = 3.6%; 95% confidence interval, 2.4%-4.8%) but not mean dose. In inverse probability weighting analysis, IMRT was associated with 29% to 48% relative reduction in percent of the heart receiving V40-V60 Gy without increasing lung or esophageal dose or compromising planning target volume coverage. CONCLUSIONS: Within MROQC, historical cardiac constraints were met in most cases, yet 1 in 4 patients received a mean heart dose exceeding 20 Gy. Future work is required to standardize heart dose constraints and to develop treatment approaches that allow for constraints to be met without compromising other planning goals.

A simulation study to assess the potential impact of developing normal tissue complication probability models with accumulated dose.

PURPOSE: This study aimed to analyze the potential clinical impact of the differences between planned and accumulated doses on the development and use of normal tissue complication probability (NTCP) models. METHODS AND MATERIALS: Thirty patients who were previously treated with stereotactic body radiation therapy for liver cancer and for whom the accumulated dose was computed were assessed retrospectively. The linear quadratic equivalent dose at 2 Gy per fraction and generalized equivalent uniform dose were calculated for planned and accumulated doses. Stomach and duodenal Lyman-Kutcher-Burman NTCP models (α/ß = 2.5; n = .09) were developed on the basis of planned and accumulated generalized equivalent uniform doses and the differences between the models assessed. In addition, the error in determining the probability of toxicity on the basis of the planned dose was evaluated by comparing planned doses in the NTCP model that were created from accumulated doses. RESULTS: The standard, planned-dose NTCP model overestimates toxicity risk for both the duodenal and stomach models at doses that are below approximately 20 Gy (6 fractions) and underestimates toxicity risk for doses above approximately 20 Gy (6 fractions). Building NTCP models with accumulated rather than planned doses changes the predicted risk by up to 16% (mean: 6%; standard deviation: 7%) for duodenal toxicity and 6% (mean: 2%; standard deviation: 2%) for stomach toxicity. For a protocol that plans a 10% iso-toxicity risk to the duodenum, a 15.7 Gy (6 fractions) maximum dose constraint would be necessary when using standard NTCP models on the basis of a planned dose and a 17.6 Gy (6 fractions) maximum dose would be allowed when using NTCP models on the basis of accumulated doses. CONCLUSIONS: Assuming that accumulated dose is a more accurate representation of the true delivered dose than the planned dose, this simulation study indicates the need for prospective clinical trials to evaluate the impact of building NTCP models on the basis of accumulated doses.

Changes in prostate orientation due to removal of a Foley catheter.

PURPOSE: Investigate the impact on prostate orientation caused by use and removal of a Foley catheter, and the dosimetric impact on men prospectively treated with prostate stereotactic body radiotherapy (SBRT). METHODS: Twenty-two men underwent a CT simulation with a Foley in place (FCT), followed immediately by a second treatment planning simulation without the Foley (TPCT). The change in prostate orientation was determined by rigid registration of three implanted transponders between FCT and TPCT and compared to measured orientation changes during treatment. The impact on treatment planning and delivery was investigated by analyzing the measured rotations during treatment relative to both CT scans, and introducing rotations of ±15° in the treatment plan to determine the maximum impact of allowed rotations. RESULTS: Removing the Foley caused a statistically significant prostate rotation (P < 0.0028) compared to normal biological motion in 60% of patients. The largest change in rotation due to removing a Foley occurs about the left-right axis (tilt) which has a standard deviation two to five times larger than changes in rotation about the Sup-Inf (roll) and Ant-Post (yaw) axes. The change in tilt due to removing a Foley for prone and supine patients was -1.1° ± 6.0° and 0.3° ± 7.4°, showing no strong directional bias. The average tilt during treatment was -1.6° ± 7.1° compared to the TPCT and would have been -2.0° ± 7.1° had the FCT been used as the reference. The TPCT was a better or equivalent representation of prostate tilt in 82% of patients, vs 50% had the FCT been used for treatment planning. However, 92.7% of fractions would still have been within the ±15° rotation limit if only the FCT were used for treatment planning. When rotated ±15°, urethra V105% = 38.85Gy  < 20% was exceeded in 27% of the instances, and prostate (CTV) coverage was maintained above D95%  > 37 Gy in all but one instance. CONCLUSIONS: Removing a Foley catheter can cause large prostate rotations. There does not appear to be a clear dosimetric benefit to obtaining the CT scan with a Foley catheter to define the urethra given the changes in urethral position from removing the Foley catheter. If urethral sparing is desired without the use of a Foley, utilization of an MRI to define the urethra may be necessary, or a pseudo-urethral planning organ at risk volume (PRV) may be used to limit dosimetric hot spots.

Does drug-induced sleep endoscopy predict surgical success in transoral robotic multilevel surgery in obstructive sleep apnea?

OBJECTIVES/HYPOTHESIS: The aim of this study was to determine if drug-induced sleep endoscopy (DISE) was predictive of success for patients undergoing transoral robotic surgery (TORS) and multilevel procedures for sleep apnea. STUDY DESIGN: Retrospective case series of patients who underwent TORS surgery for sleep apnea METHODS: Before and after polysomnograms were analyzed to assess improvement, success, and cure. Improvement was defined as any decrease in apnea-hypopnea index (AHI), success as an AHI <20 with a decrease >50%, and cure as an AHI <5. DISE videos were scored using the NOHL (nose, oropharynx, hypopharynx, larynx) and VOTE (velum, oropharynx, tongue, epiglottis) classification systems. RESULTS: One hundred one patients were available for analysis. Eighty-seven percent of patients had an improvement in their AHI. Fifty-one percent met criteria for success, whereas 17% were cured. The degree of collapse at individual NOHL and VOTE subsites as well as total additive scores did not predict improvement, success, or cure. Patients with no oropharyngeal lateral collapse in the VOTE classification system were more likely to improve following surgery (P = .001); however, this effect did not hold for success or cure. Multivariate analysis of DISE variables was not predictive of success. CONCLUSIONS: In obstructive sleep apnea patients, there is a 51% success rate and a 17% cure rate. DISE, as scored by the NOHL and VOTE system, did not readily identify patients who would benefit most from surgery. Patients with lateral oropharyngeal collapse may be poorer candidates. Prospective, larger studies are required to further evaluate the use of DISE in predicting success following TORS. LEVEL OF EVIDENCE: 4 Laryngoscope, 127:971-976, 2017.

Tumor Biomarkers in Spindle Cell Variant Squamous Cell Carcinoma of the Head and Neck.

OBJECTIVE: To determine biomarkers of recurrence and survival in patients with spindle cell variant squamous cell carcinoma (SpSCC) of the head and neck. STUDY DESIGN: Retrospective case control study. SETTING: Tertiary academic center. SUBJECTS AND METHODS: Thirty-two SpSCC patients (mean age, 68.8) between 1987 and 2009 were identified and reviewed. A tissue microarray (TMA) was constructed from tumor specimens. Tumor biomarkers under study included p16, epidermal growth factor receptor (EGFR), p53, EZH2, cyclin D1, CD104, HGFa, p21, and cMET. An additional TMA was constructed from patients with non-SpSCC oral cavity squamous cell carcinoma for comparative purposes. The main outcomes were overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS). RESULTS: In the SpSCC cohort, tumors positive for cMet had worse OS (P < .001). Patients positive for cMet (P = .007), cyclin D1 (P = .019), and p16 (P = .004) had worse DSS. Recurrence-free survival was also worse in patients with tumors positive for cMet (P = .037), cyclin D1 (P = .012), and p16 (P < .001). Compared with the oral cavity cohort, there was a significantly larger proportion of patients in the SpSCC group with tumors staining positive for cMet and a lower proportion of tumors positive for cyclin D1. CONCLUSION: cMet, cyclin D1, and p16 are predictive tumor biomarkers for risk of recurrence and worse DSS in patients with SpSCC.

Conditional survival in advanced colorectal cancer and surgery.

BACKGROUND: Recent data show patients with advanced colorectal cancer (CRC) are surviving longer. What is unknown is how specific treatment modalities affect long-term survival. Conditional survival, or survival prognosis based on time already survived, is becoming an acceptable means of estimating prognosis for long-term survivors. We evaluated the impact of cancer-directed surgery on long-term survival in patients with advanced CRC. METHODS: We used Surveillance, Epidemiology, and End Results data to identify 64,956 patients with advanced (Stage IV) CRC diagnosed from 2000-2009. Conditional survival estimates by stage, age, and cancer-directed surgery were obtained based on Cox proportional hazards regression model of disease-specific survival. RESULTS: A total of 64,956 (20.1%) patients had advanced disease at the time of diagnosis. The proportion of those patients who underwent cancer-directed surgery was 65.1% (n = 42,176). Cancer-directed surgery for patients with advanced stage disease was associated with a significant improvement in traditional survival estimates compared to patients who did not undergo surgery (hazard ratio = 2.22 [95% confidence interval, 2.17-2.27]). Conditional survival estimates show improvement in conditional 5-y disease-specific survival across all age groups, demonstrating sustained survival benefits for selected patients with advanced CRC. CONCLUSIONS: Five-year disease-specific conditional survival improves dramatically over time for selected patients with advanced CRC who undergo cancer-directed surgery. This information is important in determining long-term prognosis and will help inform treatment planning for advanced CRC.

Implications of age and conditional survival estimates for patients with melanoma.

Overall cancer incidence is decreasing, whereas melanoma cases are increasing. Conditional survival estimates offer a more accurate prognosis for patients the farther they are from time of diagnosis. The effect of age and stage on a melanoma patient's conditional survival estimate is unknown. Surveillance, Epidemiology, and End Results data were utilized to identify newly diagnosed cutaneous melanoma patients (N=95 041), from 1998 to 2005, with up to 12 years of follow-up. Estimates of disease-specific survival by stage and age were determined by Cox regression analysis and transformed to estimated conditional 5-year survival. Localized melanoma patients have an excellent 5-year survival at diagnosis and over subsequent years. For patients with localized and regional disease, an age effect is present for disease-specific mortality when comparing older patients (70-79 years) with younger patients (<30 years): hazard ratio (HR) for mortality 3.79 [95% confidence interval (CI) 3.01-4.84] and HR 2.36 (95% CI 1.93-2.91), respectively. No age effect difference is observed in disease-specific survival for advanced disease: HR 1.14 (95% CI 0.87-1.53). Over time, conditional survival estimates improve for older patients with localized and regional disease. This improvement is not seen in distant disease, neither is the age gradient. Disease-specific mortality and conditional survival for patients with localized and regional melanomas are initially impacted by older age, with effects dissipating over time. Age does not affect survival in patients with advanced disease. Understanding the conditional 5-year disease-specific survival of melanoma based on age and stage can help patients and physicians, informing decision-making about treatment and surveillance.

Trends in imaging after diagnosis of thyroid cancer.

BACKGROUND: The largest growth noted among differentiated thyroid cancer (DTC) diagnosis is in low-risk cancers. Trends in imaging after the diagnosis of DTC are understudied. Hypothesizing a reduction in imaging use due to rising low-risk disease, the authors evaluated postdiagnosis imaging patterns over time and patient characteristics that are associated with the likelihood of imaging. METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare database, the authors identified patients diagnosed with localized, regional, or distant DTC between 1991 and 2009. Medicare claims were reviewed for use of neck ultrasound, iodine-131 (I-131) scan, or positron emission tomography (PET) scan within 3 years after diagnosis. Trends in imaging use were evaluated using regression analyses. Multivariable logistic regression was used to estimate the likelihood of imaging based on patient characteristics. RESULTS: A total of 23,669 patients were included. Compared with patients diagnosed between 1991 and 2000, those diagnosed between 2001 and 2009 were more likely to have localized disease (P<.001) and tumors measuring <1 cm (P<.001). Use of neck ultrasound and I-131 scans increased in patients with localized disease (P ≤.001 and P = .003, respectively), regional disease (P<.001 and P<.001, respectively), and distant metastasis (P = .001 and P = .015, respectively). Patients diagnosed after 2000 were more likely to undergo neck ultrasound (odds ratio, 2.15; 95% confidence interval, 2.02-2.28) and I-131 scan (odds ratio, 1.44; 95% confidence interval, 1.35-1.54). Compared with 1996 through 2004, PET scan use from 2005 to 2009 increased 32.4-fold (P≤.001) in patients with localized disease, 13.1-fold (P<.001) in patients with regional disease, and 33.4-fold (P<.001) in patients with distant DTC. CONCLUSIONS: Despite an increase in the diagnosis of low-risk disease, the use of postdiagnosis imaging increased among patients with all stages of disease. The largest growth observed was in the use of PET after 2004.

Conditional survival in patients with thyroid cancer.

BACKGROUND: Thyroid cancer is an increasingly common malignancy. Although likelihood of survival from well-differentiated thyroid cancer can vary by disease severity, it is not known how patients' life expectancies change the farther they are from time of diagnosis. METHODS: Using data from the Surveillance, Epidemiology, End Results (SEER) registry, we selected patients diagnosed with well-differentiated thyroid cancer (N=43,392) between 1998 and 2005. Patients were followed for up to 12 years. Conditional survival estimates by SEER stage and age were obtained based on Cox proportional hazards regression model of disease-specific survival. RESULTS: Patients with localized thyroid cancer have excellent conditional 5-year survival, irrespective of where they are in their survivorship phase. Patients with regional thyroid cancer have relatively stable conditional 5-year survival, whereas for patients with distant thyroid cancer there is gradual improvement the farther from time of diagnosis. Age and gender influence conditional survival. Similarly, age has a strong effect on disease-specific survival for patients with thyroid cancer with localized (hazard ratio [HR] 88.7 [95% confidence interval {CI} 26.3-552), comparing age ≥80 with <30 years), regional (HR 105 [95% CI 52.6-250]), and distant disease [HR 86.8 (95% CI 32.5-354)]. Male gender is also associated with a significantly worse disease-specific survival among patients with regional disease (HR 1.56 [95% CI 1.31-1.85]) but not among patients with localized or distant disease. CONCLUSION: Cancer stage, gender, age at diagnosis, and length of time already survived can influence conditional survival for patients with thyroid cancer. Understanding the conditional 5-year disease-specific survival of well-differentiated thyroid cancer is key to creating treatment plans and tailoring surveillance.

Tree-based model for thyroid cancer prognostication.

BACKGROUND: Death is uncommon in thyroid cancer patients, and the factors important in predicting survival remain inadequately studied. The objective of this study was to assess prognostic effects of patient, tumor, and treatment factors and to determine prognostic groups for thyroid cancer survival. METHODS: Using data from the Surveillance, Epidemiology, and End Results Program (SEER), we evaluated overall and disease-specific survival (DSS) in 43 392 well-differentiated thyroid cancer patients diagnosed from 1998 through 2005. Multivariable analyses were performed using Cox proportional hazards regression, survival trees, and random survival forest. Similar analyses were performed using National Cancer Data Base data, with overall survival (OS) evaluated in 131 484 thyroid cancer patients diagnosed from 1998 through 2005. Relative importance of factors important to survival was assessed based on the random survival forest analyses. RESULTS: Using survival tree analyses, we identified 4 distinct prognostic groups based on DSS (P < .0001). The 5-year DSS of these prognostic groups was 100%, 98%, 91%, 64%, whereas the 10-year survival was 100%, 96%, 85%, and 50%. Based on random survival forest analyses, the most important factors for DSS were SEER stage and age at diagnosis. For OS, important prognostic factors were similar, except age at diagnosis demonstrated marked importance relative to SEER stage. Similar results for OS were found using National Cancer Data Base data. CONCLUSION: This study identifies distinct prognostic groups for thyroid cancer and illustrates the importance of patient age to both disease-specific and OS. These findings have implications for patient education and thyroid cancer treatment.