Observer preference of artificial intelligence-generated versus clinical prostate contours for ultrasound-based high dose rate brachytherapy.

BACKGROUND: For trans-rectal ultrasound (TRUS)-based high dose rate (HDR) prostate brachytherapy, prostate contouring can be challenging due to artifacts from implanted needles, bleeding, and calcifications. PURPOSE: To evaluate the geometric accuracy and observer preference of an artificial intelligence (AI) algorithm for generating prostate contours on TRUS images with implanted needles. METHODS: We conducted a retrospective study of 150 patients, who underwent HDR brachytherapy. These patients were randomly divided into training (104), validation (26) and testing (20) sets. An AI algorithm was trained/validated utilizing the TRUS image and reference (clinical) contours. The algorithm then provided contours for the test set. For evaluation, we calculated the Dice coefficient between AI and reference prostate contours. We then presented AI and reference contours to eight clinician observers, and asked observers to select their preference. Observers were blinded to the source of contours. We calculated the percentage of cases in which observers preferred AI contours. Lastly, we evaluate whether the presence of AI contours improved the geometric accuracy of prostate contours provided by five resident observers for a 10-patient subset. RESULTS: The median Dice coefficient between AI and reference contours was 0.92 (IQR: 0.90-0.94). Observers preferred AI contours for a median of 57.5% (IQR: 47.5, 65.0) of the test cases. For resident observers, the presence of AI contours was associated with a 0.107 (95% CI: 0.086, 0.128; p < 0.001) improvement in Dice coefficient for the 10-patient subset. CONCLUSION: The AI algorithm provided high-quality prostate contours on TRUS with implanted needles. Further prospective study is needed to better understand how to incorporate AI prostate contours into the TRUS-based HDR brachytherapy workflow.

Premetastatic shifts of endogenous and exogenous mutational processes support consolidative therapy in EGFR-driven lung adenocarcinoma.

The progression of cancer is an evolutionary process that is challenging to assess between sampling timepoints. However, investigation of cancer evolution over specific time periods is crucial to the elucidation of key events such as the acquisition of therapeutic resistance and subsequent fatal metastatic spread of therapy-resistant cell populations. Here we apply mutational signature analyses within clinically annotated cancer chronograms to detect and describe the shifting mutational processes caused by both endogenous (e.g. mutator gene mutation) and exogenous (e.g. mutagenic therapeutics) factors between tumor sampling timepoints. In one patient, we find that cisplatin therapy can introduce mutations that confer genetic resistance to subsequent targeted therapy with Erlotinib. In another patient, we trace detection of defective mismatch-repair associated mutational signature SBS3 to the emergence of known driver mutation CTNNB1 S37C. In both of these patients, metastatic lineages emerged from a single ancestral lineage that arose during therapy-a finding that argues for the consideration of local consolidative therapy over other therapeutic approaches in EGFR-positive non-small cell lung cancer. Broadly, these results demonstrate the utility of phylogenetic analysis that incorporates clinical time course and mutational signature deconvolution to inform therapeutic decision making and retrospective assessment of disease etiology.

Did quality of life for older cancer survivors improve with the turn of the century in the United States?

OBJECTIVES: Although survival after a cancer diagnosis has improved considerably over the past 20 years, little is known about trends in health-related quality-of-life (HRQOL) for older prostate, breast, and lung cancer survivors. METHODS: Using a population-based registry with longitudinal patient reported outcomes (the National Cancer Institute Surveillance, Epidemiology and End Results database linked to Medicare Health Outcomes Survey), we analyzed Medicare Advantage patients diagnosed with cancer during 1998-2011, who completed surveys regarding HRQOL through 2013. 'Early Era' patients were treated during 1998-2003; 'Late Era' patients were treated during 2006-2011. After propensity score matching, post-diagnosis changes in health utility (HU), Physical Component Summary (PCS) and Mental Component Summary (MCS) scores were calculated and compared between the two eras. RESULT: We identified 208 older patients with prostate, 276 with breast and 76 with lung cancer who were treated in the 'Early Era' and matched to equal numbers in the 'Late Era'. Mean age of patients in early and late era was 72 and 73 years, respectively. The mean post-diagnosis decline in health utility for patients treated in the 'Late Era' was not significantly different from the 'Early Era' for any cancer (Prostate [early vs. late]: -0.06 vs. -0.03, p = .09; Breast: -0.03 vs. -0.04, p = .65; Lung: -0.07 vs. -0.07, p = .95); nor for Physical Component Summary or Mental Component Summary scores. CONCLUSION: Older patients treated for prostate, breast or lung cancer in the later era reported similar outcomes of changes in HRQOL compared to earlier era patients.

Response to hyperfractionated accelerated radiotherapy in chemotherapy-refractory non-Hodgkin lymphoma.

Patients with chemotherapy-refractory non-Hodgkin lymphoma (NHL) have a poor prognosis with a median overall survival (OS) of only 10 months. To investigate the role of radiotherapy (RT) in such patients, we conducted a retrospective review of 17 patients with biopsy-proven refractory NHL who received hyperfractionated accelerated RT between 2000 and 2017. Forty-seven percent had stages I and II and 53% had stages III and IV disease. Majority (59%) had diffuse large B-cell lymphoma. One-year local control rate was 82%. Fifty-nine percent proceeded to hematopoietic stem cell transplantation (HSCT). At a median follow-up time of 8.8 months (range: 13 days to 17.4 years), 10 were alive with five in remission. Six patients were long-term survivors with a median OS of 8.1 years. Hyperfractionated accelerated RT in chemotherapy-refractory NHL provides durable local disease control in the majority of cases. Combined with HSCT, the RT regimen may also provide long-term disease remission in a subset of patients.

Outcomes of HPV-Associated Squamous Cell Carcinoma of the Head and Neck: Impact of Race and Socioeconomic Status.

BACKGROUND: Socioeconomic factors affecting outcomes of HPV-associated squamous cell carcinoma of the head and neck (SCCHN) are poorly characterized. METHODS: A custom SEER database identified adult patients with primary nonmetastatic SCCHN and known HPV status diagnosed in 2013 through 2014. Multivariable logistic regression defined associations between patient characteristics and HPV status, with adjusted odds ratios (aORs) and 95% confidence intervals reported. Fine-Gray competing risks regression estimated adjusted hazard ratios (aHRs) and 95% confidence intervals for cancer-specific mortality (CSM), including a disease subsite * HPV status * race interaction term. RESULTS: A total of 4,735 patients with nonmetastatic SCCHN and known HPV status were identified. HPV-associated SCCHN was positively associated with an oropharyngeal primary, male sex, and higher education, and negatively associated with uninsured status, single marital status, and nonwhite race (P≤.01 for all). For HPV-positive oropharyngeal SCCHN, white race was associated with lower CSM (aHR, 0.55; 95% CI, 0.34-0.88; P=.01) and uninsured status was associated with higher CSM (aHR, 3.12; 95% CI, 1.19-8.13; P=.02). These associations were not observed in HPV-negative or nonoropharynx SCCHN. Accordingly, there was a statistically significant disease subsite * HPV status * race interaction (Pinteraction<.001). CONCLUSIONS: Nonwhite race and uninsured status were associated with worse CSM in HPV-positive oropharyngeal SCCHN, whereas no such associations were observed in HPV-negative or nonoropharyngeal SCCHN. These results suggest that despite having clinically favorable disease, nonwhite patients with HPV-positive oropharyngeal SCCHN have worse outcomes than their white peers. Further work is needed to understand and reduce socioeconomic disparities in SCCHN.

Early Impact of the Affordable Care Act and Medicaid Expansion on Racial and Socioeconomic Disparities in Cancer Care.

OBJECTIVES: We sought to evaluate sociodemographic disparities in insurance coverage among nonelderly adults with a common cancer after Affordable Care Act (ACA) implementation. PATIENTS AND METHODS: In total, 109,182 patients aged 18 to 64 years diagnosed with a common cancer (lung, breast, or prostate cancer) were identified from 2010 to 2014. Multivariable logistic regressions analyzed associations between ACA implementation and uninsured rates on the basis of state approach to Medicaid expansion, stratified by race (black, white), and income (stratified at 138% Federal Poverty Line). RESULTS: Uninsured rates declined after ACA implementation, with the greatest rate reductions associated with traditional Medicaid expansion (Pinteraction <0.001). Racial disparities in insurance coverage were eliminated with traditional Medicaid expansion where the uninsured rate went from 10.0% to 0.95% among black patients (adjusted odds ratio [AOR]pre-aca 1.52 to AORpost-aca 0.47) but persisted with other state approaches (AORpre-aca 1.15 to AORpost-aca 1.12) (Pinteraction =0.002). Furthermore, socioeconomic coverage gaps were eliminated with traditional Medicaid expansion, where the uninsured rate went from 8.4% to 1.4% among low-income (≤138% Federal Poverty Line) patients, but not with other state approaches (Pinteraction <0.001). CONCLUSIONS: Traditional Medicaid expansion was associated with the elimination of racial and socioeconomic insurance coverage gaps. These results highlight the potential benefits and challenges of the ACA and its provisions, and could instruct ongoing policy.

An Update to Changing Patterns of Anal Carcinoma in the United States.

OBJECTIVES: Approximately 8,300 new cases of anal carcinoma will be diagnosed in the United States in 2019. Anal squamous cell carcinoma (SCC) accounts for about 70% of all anal cancers. As cancer prevention and treatments have evolved over time, medical management of human immunodeficiency virus has improved, and sexual behaviors have changed, anal carcinoma incidence rates (IRs) may have also changed. METHODS: The 9 oldest Surveillance, Epidemiology, and End Results registries were used to identify and determine IR of carcinoma in situ (CIS) and invasive SCC for 9757 patients below 65 years diagnosed with anal SCC/CIS from 1973 to 2014. Joinpoint regression models identified time points at which incidence trends changed. RESULTS: The incidence of CIS decreased since 2010 (age-adjusted IR annual percent change [APC]: -5.65, 95% CI: -10.0 to -1.1), especially for men (APC: -8.30, 95% CI: -12.6 to -3.8). In contrast, the incidence of SCC increased since 2007 (APC: 2.59, 95% CI: 0.1-5.2). During 2010-2014, men were more likely to present with CIS (incidence rate ratio [IRR]: 3.234, 95% CI: 3.000-3.489) but less likely to present with localized (IRR: 0.827, 95% CI: 0.754-0.906), regional (IRR: 0.603, 95% CI: 0.537-0.676), and distant SCC (IRR: 0.751, 95% CI: 0.615-0.915) compared with women. CONCLUSIONS: The previously observed rise in anal SCC/CIS incidence slowed in 2010, largely due to a decline in CIS rates. Patients were more likely to present with CIS than SCC at any stage. Future studies are necessary to determine if this decline in CIS precedes a decline in invasive SCC.

Conservative management of low-risk prostate cancer among young versus older men in the United States: Trends and outcomes from a novel national database.

BACKGROUND: Management for men aged ≤55 years with low-risk prostate cancer (LRPC) is debated given quality-of-life implications with definitive treatment versus the potential missed opportunity for cure with conservative management. The objective of this study was to define rates of conservative management for LRPC and associated short-term outcomes in young versus older men in the United States. METHODS: The nonpublic Surveillance, Epidemiology, and End Results Prostate with Active Surveillance/Watchful Waiting (AS/WW) Database identified 50,302 men who were diagnosed with LRPC from 2010 through 2015. AS/WW rates in the United States were stratified by age (≤55 vs ≥56 years). Prostate cancer-specific mortality and overall mortality were defined by initial management type (AS/WW vs definitive treatment [referent]) and age. RESULTS: AS/WW utilization increased from 8.61% (2010) to 34.56% (2015) among men aged ≤55 years (P for trend <0.001) and from 15.99% to 43.81% among men aged ≥56 years (P for trend <.001). Among patients who had ≤2 positive biopsy cores, AS/WW rates increased from 12.90% to 48.78% for men aged ≤55 years and from 21.85% to 58.01% for men aged ≥56 years. Among patients who had ≥3 positive biopsy cores, AS/WW rates increased from 3.89% to 22.45% for men aged ≤55 years and from 10.05% to 28.49% for men aged ≥56 years (all P for trend <.001). Five-year prostate cancer-specific mortality rates were <0.30% across age and initial management type subgroups. CONCLUSIONS: AS/WW rates quadrupled for patients aged ≤55 years from 2010 to 2015, with favorable short-term outcomes. These findings demonstrate the short-term safety and increasing acceptance of AS/WW for both younger and older patients. However, there are still higher absolute rates of AS/WW in older patients (P < .001), suggesting some national ambivalence toward AS/WW in younger patients.

Cardiac Complications Related to Spine Surgery: Timing, Risk Factors, and Clinical Effect.

INTRODUCTION: Large cohort studies evaluating cardiac complications in patients undergoing spine surgery are lacking. The purpose of this study was to determine the incidence, timing, risk factors, and effect of cardiac complications in spine surgery by using a national database, the American College of Surgeons National Surgical Quality Improvement Program. METHODS: Patients who underwent spine surgery in the 2005 to 2012 National Surgical Quality Improvement Program database were identified. The primary outcome was an occurrence of cardiac arrest or myocardial infarction during the operation or the 30-day postoperative period. Risk factors for development of cardiac complications were identified using multivariate regression. The postoperative length of stay, 30-day readmission, and mortality were compared between patients who did and did not experience a cardiac complication. RESULTS: A total of 30,339 patients who underwent spine surgery were identified. The incidence of cardiac complications was 0.34% (95% confidence interval [CI], 0.27% to 0.40%). Of the cases in which a cardiac complication developed, 30% were diagnosed after discharge. Risk factors for the development of cardiac complications were greater age (most notably ≥80 years, relative risk [RR] = 5.53; 95% CI = 2.28 to 13.43; P < 0.001), insulin-dependent diabetes (RR = 2.58; 95% CI = 1.51 to 4.41; P = 0.002), preoperative anemia (RR = 2.46; 95% CI = 1.62 to 3.76; P < 0.001), and history of cardiac disorders and treatments (RR = 1.88; 95% CI = 1.16 to 3.07; P = 0.011). Development of a cardiac complication before discharge was associated with a greater length of stay (7.9 versus 2.6 days; P < 0.001), and a cardiac complication after discharge was associated with increased 30-day readmission (RR = 12.32; 95% CI = 8.17 to 18.59; P < 0.001). Development of a cardiac complication any time during the operation or 30-day postoperative period was associated with increased mortality (RR = 113.83; 95% CI = 58.72 to 220.68; P < 0.001). DISCUSSION: Perioperative cardiac complications were diagnosed in approximately 1 in 300 patients undergoing spine surgery. High-risk patients should be medically optimized and closely monitored through the perioperative period. LEVEL OF EVIDENCE: Level III.

Prostate cancer outcomes for men aged younger than 65 years with Medicaid versus private insurance.

BACKGROUND: In the current national debate regarding private insurance versus Medicaid expansion, understanding how insurance is associated with racial disparities in prostate cancer (CaP) outcomes has broad policy implications. In the current study, the authors examined the association between insurance status, race, and CaP outcomes. METHODS: The Surveillance, Epidemiology, and End Results program identified 155,524 men aged < 65 years who were diagnosed with CaP from 2007 through 2014. The association between insurance and stage of disease at the time of presentation was examined. Among men with localized CaP, the associations between insurance and receipt of therapy and prostate cancer-specific mortality (PCSM) were determined. RESULTS: Compared with private insurance, men with Medicaid were more likely to present with metastatic disease (adjusted odds ratio [AOR], 4.27; 95% confidence interval [95% CI], 4.01-4.55), were less likely to receive definitive treatment (AOR, 0.67; 95% CI, 0.62-0.71), and had increased PCSM (adjusted hazard ratio, 1.83; 95% CI, 1.50-2.24), regardless of race. Significant interactions between race and insurance status indicated that insurance had more than an additive association with race. Among privately insured patients, disparities in PCSM (AOR, 1.2; 95% CI, 1.03-1.40 [P = .019]) and presentation with metastatic disease (AOR, 1.13; 95% CI, 1.06-1.21 [P<.001]) were observed. No disparities were observed among patients with Medicaid insurance with regard to PCSM (AOR, 0.79; 95% CI, 0.52-1.20 [P = .272]) and metastatic disease (AOR, 0.91; 95% CI, 0.80-1.03 [P = .139]). CONCLUSIONS: Racial disparities in the outcomes of patients with CaP were observed in privately insured cohorts, whereas these disparities appeared to be reduced among patients with Medicaid insurance. However, outcomes need to be improved overall. Whether the equality in outcomes for Medicaid is due to white and African American patients doing "equally poorly" or "equally well" is unclear. Cancer 2018;124:752-9. © 2017 American Cancer Society.

National sociodemographic disparities in the treatment of high-risk prostate cancer: Do academic cancer centers perform better than community cancer centers?

BACKGROUND: Most major cancer organizations seek to reduce sociodemographic disparities in high-risk cancers partly by increasing access to theoretically high-quality, academic-oriented cancer care. The objective of this study was to determine whether academic centers have less sociodemographic treatment disparities than community centers using high-risk prostate cancer as a test case. METHODS: The National Cancer Data Base was used to identify 138,019 patients who were diagnosed with nonmetastatic, high-risk prostate cancer from 2004 to 2012. Multivariable logistic analysis was used to identify independent determinants of definitive therapy. The Gray test and multivariable Cox regression were used to analyze the timing of therapy. All analyses were stratified by academic versus community cancer center. RESULTS: Compared with white or privately insured patients, black, Hispanic, and uninsured patients with prostate cancer were less likely to receive definitive therapy at both community centers (adjusted odds ratio: 0.60 [95% confidence interval (CI), 0.56-0.64], 0.69 [95% CI, 0.61-0.78], and 0.25 [95% CI, 0.22-0.30], respectively) and academic cancer centers (adjusted odds ratio: 0.50 [95% CI, 0.46-0.54], 0.56 [95% CI, 0.50-0.64], and 0.31 [95% CI, 0.28-0.36], respectively). Among patients who received definitive therapy, black, Hispanic, and uninsured patients were more likely to experience treatment delays at both community centers (≥15, ≥ 10, and ≥19 days, respectively; all Gray P < .001) and academic centers (≥19, ≥ 11, and ≥18 days, respectively); treatment delays were observed among the aforementioned groups even after multivariable Cox regression analysis (P < .001 for all adjusted hazard ratios). CONCLUSIONS: Nationally, academic cancer centers demonstrate similarly high rates of sociodemographic disparities in cancer treatment patterns as community cancer centers. Making community centers conform to academic center standards may not necessarily reduce treatment disparities. Cancer 2016;122:3371-3377. © 2016 American Cancer Society.