Daniel G. Muenz

Disease severity and radioactive iodine use for thyroid cancer.

CONTEXT Although variation in radioactive iodine (RAI) use for thyroid cancer has been demonstrated, the role of region and nonclinical correlates of use within risk groups has not been investigated. OBJECTIVE The objective of the study was to determine the correlates of RAI use within risk groups. DESIGN/SETTING/PATIENTS Use of RAI was evaluated across 9 US regions in 85 948 patients with well-differentiated thyroid cancer diagnosed between 2004 and 2008 at 986 hospitals associated with the US National Cancer Database. Cancers were then categorized as low risk (tumor size ≤ 1 cm and American Joint Committee on Cancer stage I disease), medium risk (neither low nor high-risk), and high risk (American Joint Committee on Cancer stage III or IV). Within each risk stratum, the role of region and nonclinical correlates of RAI use were evaluated using hierarchical logistic regression. MAIN OUTCOME MEASURE Use of RAI was measured. RESULTS Rates of RAI use varied across geographic regions from 49% to 66%. Regional differences persisted after controlling for patient and hospital characteristics and evaluating less vs more intensive regions within low-risk [odds ratio (OR) 0.36 (95% confidence interval [CI] 0.25-0.53)], medium-risk [OR 0.23 (95% CI 0.16-0.34)], and high-risk cancers [OR 0.30 (95% CI 0.19-0.49)]. Patterns of RAI use were similar in medium- and high-risk patients. The most nonclinical correlates of use were in low-risk patients. CONCLUSION Similar treatment patterns for the heterogeneous medium-risk thyroid cancer patients compared with the high-risk patients suggest more intensive management in patients with medium-risk disease. The large number of nonclinical correlates of RAI use, including region, imply controversy over indications for RAI.

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.

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.

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.

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

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.

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.

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.

Trends in Imaging after Thyroid Cancer Diagnosis

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.

Modeling adverse event counts in phase I clinical trials of a cytotoxic agent

Background/Aims The goal of phase I clinical trials for cytotoxic agents is to find the maximum dose with an acceptable risk of severe toxicity. The most common designs for these dose-finding trials use a binary outcome indicating whether a patient had a dose-limiting toxicity. However, a patient may experience multiple toxicities, with each toxicity assigned an ordinal severity score. The binary response is then obtained by dichotomizing a patient’s richer set of data. We contribute to the growing literature on new models to exploit this richer toxicity data, with the goal of improving the efficiency in estimating the maximum tolerated dose. Methods We develop three new, related models that make use of the total number of dose-limiting and low-level toxicities a patient experiences. We use these models to estimate the probability of having at least one dose-limiting toxicity as a function of dose. In a simulation study, we evaluate how often our models select the true maximum tolerated dose, and we compare our models with the continual reassessment method, which uses binary data. Results Across a variety of simulation settings, we find that our models compare well against the continual reassessment method in terms of selecting the true optimal dose. In particular, one of our models which uses dose-limiting and low-level toxicity counts beats or ties the other models, including the continual reassessment method, in all scenarios except the one in which the true optimal dose is the highest dose available. We also find that our models, when not selecting the true optimal dose, tend to err by picking lower, safer doses, while the continual reassessment method errs more toward toxic doses. Conclusion Using dose-limiting and low-level toxicity counts, which are easily obtained from data already routinely collected, is a promising way to improve the efficiency in finding the true maximum tolerated dose in phase I trials.

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/β = 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.