Thomas M. Churilla

Causes of death among cancer patients

Background The purpose of our study was to characterize the causes of death among cancer patients as a function of objectives: (i) calendar year, (ii) patient age, and (iii) time after diagnosis. Patients and methods US death certificate data in Surveillance, Epidemiology, and End Results Stat 8.2.1 were used to categorize cancer patient death as being due to index-cancer, nonindex-cancer, and noncancer cause from 1973 to 2012. In addition, data were characterized with standardized mortality ratios (SMRs), which provide the relative risk of death compared with all persons. Results The greatest relative decrease in index-cancer death (generally from > 60% to < 30%) was among those with cancers of the testis, kidney, bladder, endometrium, breast, cervix, prostate, ovary, anus, colorectum, melanoma, and lymphoma. Index-cancer deaths were stable (typically >40%) among patients with cancers of the liver, pancreas, esophagus, and lung, and brain. Noncancer causes of death were highest in patients with cancers of the colorectum, bladder, kidney, endometrium, breast, prostate, testis; >40% of deaths from heart disease. The highest SMRs were from nonbacterial infections, particularly among <50-year olds (e.g. SMR >1,000 for lymphomas, P < 0.001). The highest SMRs were typically within the first year after cancer diagnosis (SMRs 10-10,000, P < 0.001). Prostate cancer patients had increasing SMRs from Alzheimers disease, as did testicular patients from suicide. Conclusion The risk of death from index- and nonindex-cancers varies widely among primary sites. Risk of noncancer deaths now surpasses that of cancer deaths, particularly for young patients in the year after diagnosis.

Contemporary use trends and survival outcomes in patients undergoing radical cystectomy or bladder‐preservation therapy for muscle‐invasive bladder cancer

The current study was performed to examine temporal trends and compare overall survival (OS) in patients undergoing radical cystectomy (RC) or bladder‐preservation therapy (BPT) for muscle‐invasive urothelial carcinoma of the bladder.

Disparities in the management and outcome of cervical cancer in the United States according to health insurance status

INTRODUCTION Our study sought to characterize the presentation, local management and outcomes of invasive cervical cancer with regard to patient insurance status. METHODS We queried the NCI-SEER database for invasive cervical cancer cases in patients aged 18-64 from 2007 to 2011. We analyzed clinical and socioeconomic data with regard insurance status (insured, Medicaid, or uninsured). We tested for associations between patient insurance status and treatment with definitive surgery for FIGO IA2-IB1 patients, and treatment with suboptimal radiation therapy (RT) for FIGO IB2-IVA patients (other than combination external beam and brachytherapy). We evaluated overall and cause specific survival according to insurance status. RESULTS 11,714 cases were analyzed: 60% insured, 31% Medicaid, and 9% uninsured. FIGO III/IV stage at presentation was more frequent with Medicaid (40%) and uninsured (42%) compared to insured patients (28%) (p<0.001). For FIGO IA2-IB1 patients, receipt of definitive surgery was inversely associated with uninsured status (OR [95%CI]=0.65 [0.47-0.90], p<0.001) in univariable analysis; however the relationship lost significance after multivariable adjustment. For FIGO IB2-IVA patients, the use of suboptimal RT was associated with uninsured status (OR [95%CI]=1.33 [1.07-1.65], p=0.011) in adjusted analyses. Among all patients, overall mortality was increased with Medicaid (HR [95%CI]=1.16 [1.05-1.28], p=0.003) and uninsured status (HR [95%CI]=1.17 [1.01-1.34], p=0.031) in multivariable analysis. Cancer specific mortality survival trended towards significance in multivariable analyses for both Medicaid (HR [95%CI]=1.11 [1.00-1.24] and uninsured status (HR [95%CI]=1.14 [0.98-1.33]). CONCLUSIONS Disparities in cervical cancer treatment with regard to insurance status are apparent in a recent cohort of American patients. Later stage at presentation and differences in management partially account for the inferior prognostic outcomes associated with Medicaid and uninsured status.

Whole brain radiotherapy after stereotactic radiosurgery or surgical resection among patients with one to three brain metastases and favorable prognoses: a secondary analysis of EORTC 22952-26001

Background The absence of a survival benefit for whole brain radiotherapy (WBRT) among randomized trials has been attributed to a competing risk of death from extracranial disease. We re-analyzed EORTC 22952 to assess the impact of WBRT on survival for patients with controlled extracranial disease or favorable prognoses. Patients and methods We utilized Cox regression, landmark analysis, and the Kaplan-Meier method to evaluate the impact of WBRT on survival accounting for (i) extracranial progression as a time-dependent covariate in all patients and (ii) diagnosis-specific graded prognostic assessment (GPA) score in patients with primary non-small-cell lung cancer (NSCLC). Results A total of 329 patients treated per-protocol were included for analysis with a median follow up of 26 months. One hundred and fifteen (35%) patients had no extracranial progression; 70 (21%) patients had progression <90 days, 65 (20%) between 90 and 180 days, and 79 (24%) patients >180 days from randomization. There was no difference in the model-based risk of death in the WBRT group before [hazard ratio (HR) (95% CI)=0.70 (0.45-1.11), P = 0.133), or after [HR (95% CI)=1.20 (0.89-1.61), P = 0.214] extracranial progression. Among 177 patients with NSCLC, 175 had data available for GPA calculation. There was no significant survival benefit to WBRT among NSCLC patients with favorable GPA scores [HR (95% CI)=1.10 (0.68-1.79)] or unfavorable GPA scores [HR (95% CI)=1.11 (0.71-1.76)]. Conclusions Among patients with limited extracranial disease and one to three brain metastases at enrollment, we found no significant survival benefit to WBRT among NSCLC patients with favorable GPA scores or patients with any histology and controlled extracranial disease status. This exploratory analysis of phase III data supports the practice of omitting WBRT for patients with limited brain metastases undergoing SRS and close surveillance. Clinical Trials Number NCT00002899.

Bladder Preservation Therapy: A Review of the Literature and Future Directions

Trimodal bladder preservation therapy (ie, transurethral resection followed by chemoradiotherapy) may be an acceptable treatment alternative to radical cystectomy with urinary diversion in the carefully selected patient with muscle invasive bladder cancer. Although no head-to-head randomized controlled trials have been performed, large retrospective cohort reviews and observational data analyses suggest comparable oncologic outcomes in select patients with the additional benefit of maximizing quality of life and maintaining the patients native bladder. In this review, we discuss the evolution and clinical outcomes of bladder preservation therapy, highlighting its role in the contemporary management of muscle invasive bladder cancer.

Risk of radiation pneumonitis in patients receiving taxane-based trimodality therapy for locally advanced esophageal cancer

PURPOSE There are limited data regarding clinical and treatment factors associated with radiation pneumonitis (RP) in patients receiving taxane-based trimodality therapy for esophageal cancer. The purpose of this study was to identify predictors of RP in patients undergoing trimodality therapy. METHODS AND MATERIALS We retrospectively reviewed patients undergoing chemoradiation followed by esophagectomy between 2006 and 2011. The association between clinical and dosimetric factors with RP was assessed using χ2 test and Mann-Whitney U test. Multivariable regression was used to assess the relationship between grade 2+ RP and clinical/dosimetric factors. Receiver operator curves were generated to identify threshold doses for RP. RESULTS A total of 139 patients were included; 19 (13.7%) patients experienced grade 2+ RP. Patients with upper/middle thoracic tumors (P = .038) and receiving higher radiation doses (P = .038) were more likely to develop grade 2+ RP. There was no association between taxane-based therapy and grade 2+ RP (P = .728). The percent volume of lung receiving 5 Gy (V5; P < .001), 10 Gy (P < .001), 20 Gy (V20; P < .001), and 30 Gy (P < .001) was associated with an increased risk of grade 2+ RP. On multivariable regression, the lung V5 (odds ratio, 1.101; 95% confidence interval, 1.1014-1.195) and V20 (odds ratio, 1.149; 95% confidence interval, 1.1015-1.301) remained associated with grade 2+ RP. A V5 ≤65% and V20 ≤25% were identified as optimal thresholds for increased grade 2+ RP. CONCLUSIONS Dosimetric parameters are strong predictors of symptomatic RP in patients undergoing trimodality therapy for esophageal cancer. Mitigating the risk of RP in these patients should be an important consideration during treatment planning.

Disparities in the Local Management of Breast Cancer in the US according to Health Insurance Status

Although standard practice guidelines for breast cancer are clear, the interplay between insurance and practice patterns for the US is poorly defined. This study was performed to test for associations between patient insurance status and presentation of breast cancer as well as local therapy patterns in the US, via a large national dataset. We queried the NCI Surveillance, Epidemiology, and End Results data base for breast cancer cases diagnosed from 2007 to 2011 in women aged 18–64 with nonmetastatic ductal/lobular cancers, treated surgically. We tested for associations between insurance status (insured/Medicaid/uninsured) and choice of surgical procedure (mastectomy/breast conserving surgery [BCS]), omission of radiotherapy (RT) following BCS, and administration of post‐mastectomy radiation (PMRT). There were 129,565 patients with localized breast cancer analyzed. The health insurance classification included insured (84.5%), Medicaid (11.5%), uninsured (2.1%) and unknown (1.9%). Medicaid or uninsured status was associated with large, node positive tumors, black race, and low income. The BCS rate varied by insurance status: insured (52.2%), uninsured (47.7%), and Medicaid (45.2%), p < 0.001. In multivariable analysis, Medicaid insurance remained significantly associated with receipt of mastectomy (OR [95% CI] = 1.07 [1.03–1.11]), while RT was more frequently omitted after BCS in both Medicaid (OR [95% CI] = 1.14 [1.07–1.21]) and uninsured (OR [95% CI] = 1.29 [1.14–1.47]) patients. Insurance status was associated with significant variations in breast cancer care in the US. Although patient choice cannot be determined from this dataset, departure from standard of care is associated with specific types of insurance coverage. Further investigation into the reasons for these departures is strongly suggested.

Evaluation of prediction strategy and care coordination for COPD readmissions

ABSTRACT Objectives: Factors that influence the likelihood of readmission for chronic obstructive pulmonary disease (COPD) patients and the impact of posthospital care coordination remain uncertain. LACE index (L = length of stay, A = Acuity of admission; C = Charlson comorbidity index; E = No. of emergency department (ED) visits in last 6 months) is a validated tool for predicting 30-days readmissions for general medicine patients. We aimed to identify variables predictive of COPD readmissions including LACE index and determine the impact of a novel care management process on 30-day all-cause readmission rate. Methods: In a case-control design, potential readmission predictors including LACE index were analyzed using multivariable logistic regression for 461 COPD patients between January-October 2013. Patients with a high LACE index at discharge began receiving care coordination in July 2013. We tested for association between readmission and receipt of care coordination between July-October 2013. Care coordination consists of a telephone call from the care manager who: 1) reviews discharge instructions and medication reconciliation; 2) emphasizes importance of medication adherence; 3) makes a follow-up appointment with primary care physician within 1–2 weeks and; 4) makes an emergency back-up plan. Results: COPD readmission rate was 16.5%. An adjusted LACE index of ≥ 13 was not associated with readmission (p = 0.186). Significant predictors included female gender (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.29–0.91, p = 0.021); discharge to skilled nursing facility (OR 3.03, 95% CI 1.36–6.75, p = 0.007); 4–6 comorbid illnesses (OR 9.21, 95% CI 1.17–76.62, p = 0.035) and ≥ 4 ED visits in previous 6 months (OR 6.40, 95% CI 1.25–32.87, p = 0.026). Out of 119 patients discharged between July-October 2013, 41% received the care coordination. The readmission rate in the intervention group was 14.3% compared to 18.6% in controls (p = 0.62). Conclusions: Factors influencing COPD readmissions are complex and poorly understood. LACE index did not predict 30-days all-cause COPD readmissions. Posthospital care coordination for transition of care from hospital to the community showed a 4.3% reduction in the 30-days all-cause readmission rate which did not reach statistical significance (p = 0.62).

The role of adjuvant radiation in lymph node positive endometrial adenocarcinoma

OBJECTIVES The purpose of this study was to examine the impact of adjuvant radiation on overall survival (OS) and cancer specific survival (CSS) in patients with lymph node (LN) positive endometrial cancer. METHODS We analyzed all women diagnosed with FIGO stage IIIC endometrial adenocarcinoma in the Surveillance, Epidemiology, and End Results database from 2004 to 2012 (n=2177). Patients not undergoing surgery or with missing treatment information were excluded. Chi-squared tests were used to compare predictors of treatment received. Cox proportional hazards model and Kaplan-Meier method were used to assess OS and CSS. RESULTS The median age was 60 (27-84) and the median follow-up was 31months (2-107). Adjuvant radiation was administered to 1248 (60.3%) patients. A total of 1363 (65.9%) patients had pelvic LN involvement while 658 (31.8%) had para-aortic involvement. The 3-year actuarial OS for patients with and without radiation was 80.5% and 67.6%, respectively (p<0.001). The 3-year actuarial CSS for patients with and without radiation was 83.4% and 73%, respectively (p<0.001). On multivariable analysis, receipt of radiotherapy remained associated with OS (HR 0.61 95% CI 0.51-0.74) and CSS (HR 0.65, 95% CI 0.53-0.80). After propensity matching, radiotherapy continued to be associated with an improved OS (HR 0.65 95% CI 0.54-0.78) and CSS (HR 0.65 95% CI 0.53-0.81). The addition of brachytherapy was not associated with OS or CSS. CONCLUSIONS In this large population registry analysis, adjuvant radiation was associated with improved OS and CSS in patients with LN positive endometrial cancer. Prospective data is needed to confirm these findings.

ASTRO APEx® and RO-ILS™ are applicable to medical malpractice in radiation oncology

AIM To analyze malpractice trials in radiation oncology and assess how ASTRO APEx® and RO-ILS™ apply to such cases. METHODS The Westlaw database was reviewed using PICOS/PRISMA methods. Fishers exact and Mann-Whitney U tests were used to find factors associated with outcomes. RESULTS Of 34 cases identified, external beam was used in 26 (77%). The most common factors behind malpractice were excessive toxicity (80%) and lack of informed consent (66%). ASTRO APEx pillars and ROI-LS had applicability to all but one case. Factors favoring the defendant included statute of limitations (odds ratio: 8.1; 95% CI: 1.3-50); those favoring the plaintiff included patient death (odds ratio: 0.7; 95% CI: 0.54-0.94). CONCLUSION APEx and RO-ILS are applicable to malpractice trials in radiation oncology.