PSA Stratification for Predicting Advanced Prostate Cancer Events in Men Approaching Age-Limits for Recommended Screening.

PURPOSE: To quantify the ability of various PSA values in predicting the likelihood of developing metastatic or fatal prostate cancer in older men. MATERIALS/METHODS: We used a random sample of patients in the United States Veterans Health Administration to identify 80,706 men who had received PSA testing between ages 70 to 75. Our primary endpoint was time to development of either metastatic prostate cancer or death from prostate cancer. We used cumulative/dynamic modeling to account for competing events (death from non-prostate cancer causes) in studying both the discriminative ability of PSA as well as for positive predictive value and negative predictive value at three time points. RESULTS: PSA demonstrated time-dependent predictive discrimination, with receiver operating characteristic area under the curve at 5, 10, and 14 years decreasing from 0.83 to 0.77 to 0.73, respectively, but without statistically significant difference when stratified by race. At PSA thresholds between 1 and 8 ng/mL, the positive predictive value of developing advanced prostate cancer was significantly greater in Black than White patients. For instance, at a PSA > 3, at 5, 10, and 14 years, White patients had 2.4%, 2.9%, and 3.7% risk of an event, whereas Black patients had 4.3%, 6.5%, and 8.3% risk. CONCLUSIONS: In men aged 70 to 75 deciding whether to cease PSA testing with borderline-elevated PSA values, the risk of developing metastatic or fatal prostate cancer is quantifiable and relatively low. Risk assessment in this setting must account for the higher incidence of prostate cancer in Black men.

Association Between Primary Care Use Prior to Cancer Diagnosis and Subsequent Cancer Mortality in the Veterans Affairs Health System.

Importance: Primary care physicians (PCPs) are significant contributors of early cancer detection, yet few studies have investigated whether consistent primary care translates to improved downstream outcomes. Objective: To evaluate the association of prediagnostic primary care use with metastatic disease at diagnosis and cancer-specific mortality (CSM). Design, Setting, and Participants: This cohort study used databases with primary care and referral linkage from multiple Veterans' Affairs centers from 2004 to 2017 and had a 68-month median follow-up. Analysis was completed between July 2021 and September 2022. Participants included veterans older than 39 years who had been diagnosed with 1 of 12 cancers. Inclusion criteria included known clinical staging, survival follow-up, cause of death, and receiving care at the Veterans Affairs health system (VA). Exposures: Prediagnostic PCP use, measured in the 5 years prior to diagnosis. PCP visits were binned into none (0 visits), some (1-4 visits), and annual (5 visits). Main Outcomes and Measures: Metastatic disease at diagnosis, cancer-specific mortality (CSM) for entire cohort and stratified by tumor subtype. Results: Among 245 425 patients representing 12 tumor subtypes, mean age was 65.8 (9.3) years, and the cohort skewed male (97.6%), and White (76.1%), with higher levels of comorbidity (58.6% with Charlson Comorbidity Index scores ≥2). Compared with no prior visit, some PCP use was associated with 26% decreased odds of metastatic disease at diagnosis (odds ratio [OR], 0.74; 95% CI, 0.71-0.76; P < .001) and 12% reduced risk of CSM (subdistribution hazard ratio [SHR], 0.88; 95% CI, 0.86-0.89; P < .001). Annual PCP use was associated with 39% decreased odds of metastatic disease (OR, 0.61; 95% CI, 0.59-0.63; P < .001) and 21% reduced risk of CSM (SHR, 0.79; 95% CI, 0.77-0.81; P < .001). Among tumor subtypes, prostate cancer had the largest effect size for prior PCP use on metastatic disease at diagnosis (OR for annual use, 0.32; 95% CI, 0.30-0.35; P < .001) and CSM (SHRfor annual use, 0.51; 95% CI, 0.48-0.55; P < .001). Conclusions and Relevance: In this cohort study, increased primary care use before cancer diagnosis was associated with significant decreases in metastatic disease at diagnosis and cancer-related death, with potentially the greatest difference from annual use. PCPs play a vital role in cancer prevention, and additional resources should be allocated to assist these physicians.

Association Between Prostate-Specific Antigen Screening and Prostate Cancer Mortality Among Non-Hispanic Black and Non-Hispanic White US Veterans.

Importance: Black men have higher prostate cancer incidence and mortality than non-Hispanic White men. However, Black men have been underrepresented in clinical trials of prostate-specific antigen (PSA) screening; thus, there is a lack of data to guide screening recommendations for this population. Objective: To assess whether PSA screening is associated with reduced risk of prostate cancer-specific mortality (PCSM) among non-Hispanic Black men. Design, Setting, and Participants: This retrospective cohort study used data from the US Veterans Health Administration Informatics and Computing Infrastructure for men aged 55 to 69 years who self-identified as non-Hispanic Black or non-Hispanic White and were diagnosed with intermediate-, high-, or very high-risk prostate cancer from January 1, 2004, to December 31, 2017. Data were analyzed from August 2021 to March 2022. Exposures: Prostate-specific antigen screening rate, defined as the percentage of years in which PSA screening was conducted during the 5 years before diagnosis of prostate cancer. Main Outcomes and Measures: The primary outcome was risk of PCSM among Black men and White men. The association between PSA screening and risk of PCSM was assessed using Fine-Gray regression analysis. Risk of PCSM was also assessed categorically among patients classified as having no prior PSA screening, some screening (less than annual), or annual screening in the 5 years before diagnosis. Results: The study included 45 834 veterans (mean [SD] age, 62.7 [3.8] years), of whom 14 310 (31%) were non-Hispanic Black men and 31 524 (69%) were non-Hispanic White men. The PSA screening rate was associated with a lower risk of PCSM among Black men (subdistribution hazard ratio [sHR], 0.56; 95% CI, 0.41-0.76; P = .001) and White men (sHR, 0.58; 95% CI, 0.46-0.75; P = .001). On subset analysis, annual screening (vs some screening) was associated with a significant reduction in risk of PCSM among Black men (sHR, 0.65; 95% CI, 0.46-0.92; P = .02) but not among White men (sHR, 0.91; 95% CI, 0.74-1.11; P = .35). Conclusions and Relevance: In this cohort study, PSA screening was associated with reduced risk of PCSM among non-Hispanic Black men and non-Hispanic White men. Annual screening was associated with reduced risk of PCSM among Black men but not among White men, suggesting that annual screening may be particularly important for Black men. Further research is needed to identify appropriate populations and protocols to maximize the benefits of PSA screening.

Evaluating High-Dimensional Machine Learning Models to Predict Hospital Mortality Among Older Patients With Cancer.

PURPOSE: Older hospitalized cancer patients face high risks of hospital mortality. Improved risk stratification could help identify high-risk patients who may benefit from future interventions, although we lack validated tools to predict in-hospital mortality for patients with cancer. We evaluated the ability of a high-dimensional machine learning prediction model to predict inpatient mortality and compared the performance of this model to existing prediction indices. METHODS: We identified patients with cancer older than 75 years from the National Emergency Department Sample between 2016 and 2018. We constructed a high-dimensional predictive model called Cancer Frailty Assessment Tool (cFAST), which used an extreme gradient boosting algorithm to predict in-hospital mortality. cFAST model inputs included patient demographic, hospital variables, and diagnosis codes. Model performance was assessed with an area under the curve (AUC) from receiver operating characteristic curves, with an AUC of 1.0 indicating perfect prediction. We compared model performance to existing indices including the Modified 5-Item Frailty Index, Charlson comorbidity index, and Hospital Frailty Risk Score. RESULTS: We identified 2,723,330 weighted emergency department visits among older patients with cancer, of whom 144,653 (5.3%) died in the hospital. Our cFAST model included 240 features and demonstrated an AUC of 0.92. Comparator models including the Modified 5-Item Frailty Index, Charlson comorbidity index, and Hospital Frailty Risk Score achieved AUCs of 0.58, 0.62, and 0.71, respectively. Predictive features of the cFAST model included acute conditions (respiratory failure and shock), chronic conditions (lipidemia and hypertension), patient demographics (age and sex), and cancer and treatment characteristics (metastasis and palliative care). CONCLUSION: High-dimensional machine learning models enabled accurate prediction of in-hospital mortality among older patients with cancer, outperforming existing prediction indices. These models show promise in identifying patients at risk of severe adverse outcomes, although additional validation and research studying clinical implementation of these tools is needed.

Outcomes by time to definitive chemoradiation treatment for patients with muscle-invasive bladder cancer.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has raised concerns about delaying treatment for localized cancer and its impact on long-term outcomes. OBJECTIVE: We aimed to investigate the impact of time to chemoradiation (CRT) on recurrence and survival outcomes for patients with muscle-invasive bladder cancer (MIBC). METHODS: In the national Veterans Affairs' database, we identified patients with urothelial histology, MIBC (T2-4a/N0-3/M0) diagnosed between 2000 to 2018 and treated with definitive CRT. Time to treatment was defined as the number of days between date of diagnosis and start date of CRT. The cohort was stratified into < 90 (early) or ≥ 90 days (delayed) groups. Endpoints of locoregional failure (LRF), distant failure (DF), overall survival (OS), and bladder cancer-specific survival (BCS) were evaluated in multivariable Cox and Fine-Gray models. RESULTS: 305 patients with MIBC underwent CRT - 190 (62.3%) received early CRT, 115 (37.7%) received delayed CRT. Multivariable analysis (including success of transurethral resection of bladder tumor and type of chemotherapy) revealed no difference in recurrence between groups - LRF HR 1.12 (95%CI 0.76-1.67, P = 0.56) and DF HR 1.03 (95%CI 0.70-1.53, P = 0.88). Similarly, there were no differences in survival outcomes. The lack of association was maintained at both earlier and later time cutoffs (60-120 days). CONCLUSIONS: Our findings suggest that a short-term delay in definitive therapy may not affect long-term outcomes for patients with MIBC undergoing CRT. This study does not endorse delays in therapy, but rather provides information to aid patients and clinicians navigate the unique challenges of MIBC care in both pandemic and non-pandemic times.

Treatment Discontinuation in Patients With Muscle-Invasive Bladder Cancer Undergoing Chemoradiation.

PURPOSE: Chemoradiation (CRT) is a definitive treatment option for muscle-invasive bladder cancer (MIBC). Despite its effectiveness, CRT is underused, in part owing to concerns of tolerability and the need for integrated multidisciplinary care. We investigated factors associated with and the impact of treatment discontinuation in patients with MIBC treated with CRT. METHODS AND MATERIALS: In the US Veterans Affairs' national database, we identified patients with urothelial histology, MIBC (T2-4a/N0-3/M0) diagnosed between 2000 and 2018 and treated with definitive-intent CRT. The primary endpoint of discontinued radiation was evaluated in a multivariable logistic regression. Secondary endpoints of 30-day and 90-day mortality, overall mortality, and nonbladder cancer mortality were evaluated in multivariable models. RESULTS: Of 369 veterans with MIBC who underwent CRT, 30 patients (8.1%) did not complete radiation. The most common reasons for treatment discontinuation included comorbidities or infections necessitating hospital admission (63.3%) and treatment intolerance or declining performance status (26.7%). In multivariable logistic regression, variables associated with radiation discontinuation were creatinine clearance ≤ 50 (odds ratio [OR], 3.93; 95% CI, 1.63-9.50; P = .002), incomplete transurethral resection of bladder tumor (TURBT) (OR, 3.16; 95% CI, 1.15-8.63; P = .02), and nonpreferred chemotherapy (OR, 3.31; 95% CI, 1.31-8.36; P = .01). In the cohort that discontinued radiation, 30-day mortality was 33.3% and 90-day mortality was 50.0%, with the majority of deaths attributed to nonbladder cancer causes. No patient or tumor variables were associated with either endpoint. In the cohort that completed radiation, 30-day mortality was 2.7% and 90-day mortality was 6.8%. In multivariable analysis, radiation discontinuation was associated with worse overall mortality (hazard ratio [HR], 2.48; 95% CI, 1.36-4.50; P = .003) and worse nonbladder cancer mortality (HR, 2.32; 95% CI, 1.24-4.34; P = .008). CONCLUSIONS: With a low rate of treatment discontinuation, CRT is an effective and feasible treatment option for the typically elderly and comorbid population of patients with MIBC. In addition to identified predictors of treatment discontinuation (poor renal function, incomplete TURBT, etc.), further research is required to develop evidence-based guidelines for optimal patient selection.

Patterns of Failure After Definitive Treatment of T4a Larynx Cancer.

OBJECTIVE: Recurrence is known to predict laryngeal squamous cell cancer (LSCC) survival. Recurrence patterns in T4a LSCC are poorly characterized and represent a possible explanation for observed survival discrepancies by treatment rendered. STUDY DESIGN: Retrospective database review. SETTING: Veterans Affairs national database. METHODS: Patients with T4a LSCC between 2000 and 2017 were identified and stratified by treatment (chemoradiotherapy [CRT] vs total laryngectomy + neck dissection + adjuvant therapy [surgical]). Primary outcomes were locoregional and distant recurrence. Secondary outcomes of overall mortality, larynx cancer mortality, and noncancer mortality were evaluated in Cox and Fine-Gray models. RESULTS: A total of 1043 patients had comparable baseline demographics: 438 in the CRT group and 605 in the surgical group. Patients undergoing CRT had higher proportions of node positivity (64.6% vs 53.1%, P < .001). Locoregional and distant recurrence were less common in the surgical group (23.0% vs 37.2%, P < .001; 6.8% vs 13.3%, P < .001, respectively); however, distant metastatic rates did not differ within the N0 subgroup (P = .722). On multivariable regression, surgery demonstrated favorable locoregional recurrence (hazard ratio [HR], 0.49; 95% CI, 0.39-0.62; P < .001), distant recurrence (HR, 0.47; 95% CI, 0.31-0.71; P < .001), overall mortality (HR, 0.75; 95% CI, 0.64-0.87; P < .001), and larynx cancer mortality (HR, 0.69; 95% CI, 0.56-0.85; P < .001). CONCLUSION: T4a LSCC survival discrepancies between surgical and nonsurgical treatment are influenced by varying recurrence behaviors. Surgery was associated with superior disease control and improved survival. Beyond the known benefit in locoregional control with surgery, there may be a protective effect on distant recurrence that depends on regional disease burden.

Frailty Index as a Predictor of Readmission in Patients With Head and Neck Cancer.

OBJECTIVE: To evaluate the predictive utility of the Hospital Frailty Risk Score (HFRS), a stratification tool based on the ICD-10 (International Classification of Disease, Tenth Revision), and other risk factors for 30-day readmissions and mortality in a nationally representative cohort. STUDY DESIGN: Retrospective database review. SETTING: Nationwide Readmissions Database (2017). METHODS: Patients with head and neck cancer who underwent major surgical procedures were identified from the 2017 Nationwide Readmissions Database, representing 116 medical centers nationwide. Bivariate and multivariable logistic regression methods were used to identify factors associated with unplanned 30-day readmission, 30-day readmission mortality, and increased length of hospital stay. RESULTS: A total of 14,420 patients underwent major head and neck cancer surgery. Unplanned readmission occurred in 11% of patients. The most common reasons for unplanned readmission were procedural complications (26.5%), sepsis (7.3%), and respiratory failure (3.9%). Elevated frailty index (HFRS ≥5) was identified in 22% of patients. Frailty was associated with higher 30-day readmission rates (18.0% vs 9.5%, P < .01), which held on multivariate modeling (odds ratio [OR], 1.59 [95% CI, 1.37-1.85]). Frail patients spent more days in the hospital (8.2 vs 6.8, P = .02) and incurred more charges across hospital stays ($275,000 vs $188,000, P < .01). Patients >75 years old (OR, 1.26 [1.03-1.55]) and patients with electrolyte abnormalities (OR, 1.25 [1.07-1.46] were significantly more likely to be readmitted. CONCLUSION: In this head and neck cancer surgical population, HFRS significantly predicted unplanned readmission. HFRS is a potential risk stratification tool and should be compared with other methods and explored in other cancer populations. Beyond the challenge of identifying at-risk patients, future work should explore potential interventions aimed at mitigating readmission.

Evaluating Prostate-Specific Antigen Screening for Young African American Men With Cancer.

BACKGROUND: Despite higher risks associated with prostate cancer, young African American men are poorly represented in prostate-specific antigen (PSA) trials, which limits proper evidence-based guidance. We evaluated the impact of PSA screening, alongside primary care provider utilization, on prostate cancer outcomes for these patients. METHODS: We identified African American men aged 40-55 years, diagnosed with prostate cancer between 2004 and 2017 within the Veterans Health Administration. Inverse probability of treatment-weighted propensity scores were used in multivariable models to assess PSA screening on PSA levels higher than 20, Gleason score of 8 or higher, and metastatic disease at diagnosis. Lead-time adjusted Fine-Gray regression evaluated PSA screening on prostate cancer-specific mortality (PCSM), with noncancer death as competing events. All statistical tests were 2-sided. RESULTS: The cohort included 4726 patients. Mean age was 51.8 years, with 84-month median follow-up. There were 1057 (22.4%) with no PSA screening prior to diagnosis. Compared with no screening, PSA screening was associated with statistically significantly reduced odds of PSA levels higher than 20 (odds ratio [OR] = 0.56, 95% confidence interval [CI] = 0.49 to 0.63; P < .001), Gleason score of 8 or higher (OR = 0.78, 95% CI = 0.69 to 0.88; P < .001), and metastatic disease at diagnosis (OR = 0.50, 95% CI = 0.39 to 0.64; P < .001), and decreased PCSM (subdistribution hazard ratio = 0.52, 95% CI = 0.36 to 0.76; P < .001). Primary care provider visits displayed similar effects. CONCLUSIONS: Among young African American men diagnosed with prostate cancer, PSA screening was associated with statistically significantly lower risk of PSA levels higher than 20, Gleason score of 8 or higher, and metastatic disease at diagnosis and statistically significantly reduced risk of PCSM. However, the retrospective design limits precise estimation of screening effects. Prospective studies are needed to validate these findings.

Association of Health-Care System and Survival in African American and Non-Hispanic White Patients With Bladder Cancer.

BACKGROUND: African American patients with bladder cancer have inferior outcomes compared with non-Hispanic White (White) patients. We hypothesize that access to health care is a primary determinant of this disparity. We compared outcomes by race for patients with bladder cancer receiving care within the predominant hybrid-payer health-care model of the United States captured in the Surveillance, Epidemiology, and End Results (SEER) database with those receiving care within the equal-access model of the Veterans' Health Administration (VHA). METHODS: African American and White patients diagnosed with bladder cancer were identified in SEER and VHA. Stage at presentation, bladder cancer-specific mortality (BCM), and overall survival (OS) were compared by race within each health-care system. RESULTS: The SEER cohort included 122 449 patients (93.7% White, 6.3% African American). The VHA cohort included 36 322 patients (91.0% White, 9.0% African American). In both cohorts, African American patients were more likely to present with muscle-invasive disease and metastases, but the differences between races were statistically significantly smaller in VHA. In SEER multivariable models, African American patients had worse BCM (hazard ratio [HR] = 1.22, 95% confidence interval [CI] = 1.15 to 1.29) and OS (HR = 1.26, 95% CI = 1.20 to 1.31). In contrast within the VHA, African American patients had similar BCM (HR = 0.97, 95% CI = 0.88 to 1.07) and OS (HR = 0.99, 95% CI = 0.93 to 1.05). CONCLUSIONS: In this study of contrasting health-care models, receiving medical care in an equal-access system was associated with reduced differences in stage at presentation and eliminated disparities in survival outcomes for African American patients with bladder cancer. Our findings highlight the importance of reducing financial barriers to care to notably improve health equity and oncologic outcomes for African American patients.

Impact of underlying malignancy on emergency department utilization and outcomes.

PURPOSE: Cancer patients frequently utilize the emergency department (ED) for a variety of diagnoses both related to and unrelated to their cancer, yet ED outcomes for cancer patients are not well documented. This study sought to define risks and identify predictors for inpatient admission and hospital mortality among cancer patients presenting to the ED. PATIENTS AND METHODS: We utilized the National Emergency Department Sample to identify patients with and without a diagnosis of cancer presenting to the ED between January 2016 and December 2018. We used multivariable mixed-effects logistic regression models to assess the influence of cancer on outcomes of hospital admission after the ED visit and hospital mortality for the whole patient cohort and individual presenting diagnoses. RESULTS: There were 340 million weighted ED visits, of which 8.3 million (2.3%) were associated with a cancer diagnosis. Compared to non-cancer patients, patients with cancer had an increased risk of inpatient admission (64.7% vs. 14.8%; p < 0.0001) and hospital mortality (4.6% vs. 0.5%; p < 0.0001). For each of the top 15 presenting diagnoses, cancer patients had increased risks of hospitalization (odds ratio [OR] range 2.0-13.2) or death (OR range 2.1-14.4). Although our dataset does not contain reliable estimation of stage, cancer site was the most robust individual predictor associated with the risk of hospitalization or death compared to other clinical or system-related factors. CONCLUSIONS: Cancer patients in the ED have high risks for hospital admission and death when compared to patients without cancer. Cancer patients represent a distinct population and may benefit from cancer-specific risk stratification or focused interventions to improve outcomes.

Pancreatic Cancer-Related Mutational Burden Is Not Increased in a Patient Cohort With Clinically Severe Chronic Pancreatitis.

INTRODUCTION: Chronic pancreatitis is associated with an increased risk of developing pancreatic cancer, and patients with inherited forms of pancreatitis are at greatest risk. We investigated whether clinical severity of pancreatitis could also be an indicator of cancer risk independent of etiology by performing targeted DNA sequencing to assess the mutational burden in 55 cancer-associated genes. METHODS: Using picodroplet digital polymerase chain reaction and next-generation sequencing, we reported the genomic profiles of pancreases from severe clinical cases of chronic pancreatitis that necessitated palliative total pancreatectomy with islet autotransplantation. RESULTS: We assessed 57 tissue samples from 39 patients with genetic and idiopathic etiologies and found that despite the clinical severity of disease, there was no corresponding increase in mutational burden. The average allele frequency of somatic variants was 1.19% (range 1.00%-5.97%), and distinct regions from the same patient displayed genomic heterogeneity, suggesting that these variants are subclonal. Few oncogenic KRAS mutations were discovered (7% of all samples), although we detected evidence of frequent cancer-related variants in other genes such as TP53, CDKN2A, and SMAD4. Of note, tissue samples with oncogenic KRAS mutations and samples from patients with PRSS1 mutations harbored an increased total number of somatic variants, suggesting that these patients may have increased genomic instability and could be at an increased risk of developing pancreatic cancer. DISCUSSION: Overall, we showed that even in those patients with chronic pancreatitis severe enough to warrant total pancreatectomy with islet autotransplantation, pancreatic cancer-related mutational burden is not appreciably increased.

Hypofractionated radiation therapy as palliative management for symptomatic and local control of advanced thoracic malignancies.

BACKGROUND: Radiation therapy plays an important role for symptom palliation for intrathoracic malignancies ineligible for curative-intent therapy. Limited data exists regarding the role of stereotactic body radiation therapy (SBRT) versus conformal radiation in intrathoracic tumors for palliation. We report the efficacy of hypofractionated RT (or palliative SBRT) in the symptom management and durable control of lung and non-lung intrathoracic tumors. METHODS: We performed a retrospective review of ninety-two thoracic lesions across 76 patients who completed palliative SBRT with doses ranging 25-50 Gy in 5-10 fractions between 2009 and 2019. Symptoms (cough, chest pain, hemoptysis, shortness of breath) were assessed at consult and 1-6 months follow-up. Local control was evaluated using follow-up CT imaging via RECIST criteria. Descriptive statistics were used to evaluate symptom palliation and Kaplan-Meier method to analyze local control. RESULTS: Of primary lung (Cohort P) lesions, 40% showed stable symptoms, 30% never developed symptoms, and 19% showed symptom relief. CT imaging 1-6 months post-SBRT showed 91% with partial response (PR) or stable disease (SD) in Cohort P and 87% with PR or SD in metastatic (Cohort M) lesions. In patients with initial PR/SD, local control until death was achieved in 71% of Cohort P and 84% of Cohort M. Of our symptomatic patients (Cohort S), 98% showed no symptom progression post-radiotherapy. All patients with hemoptysis at presentation achieved hemostasis post-radiotherapy. CONCLUSIONS: Palliative SBRT has the advantage of higher biologic dose without protracted course for patients with limited prognosis. Patients showed significant symptom palliation and long-term local control. Palliative SBRT represents a reasonable treatment modality for incurable thoracic malignancies.

Prognostic Utility of Pretreatment Neutrophil-Lymphocyte Ratio in Advanced Larynx Cancer.

PURPOSE: Neutrophil-lymphocyte ratio has been explored as a prognosticator in several cancer types, but its association with larynx cancer outcomes is not well known. We aimed to identify an optimal NLR cutoff point and examine the prognostic utility of this biomarker in patients with locoregionally advanced larynx cancer treated with curative intent. METHODS: In the Veterans Affairs' (VA) national database, we identified patients with locoregionally advanced (T3-4N0-3M0) laryngeal squamous cell carcinoma diagnosed between 2000 and 2017 and treated with curative intent. NLR cutoff points were calculated using Contal/O'Quigley's method. Outcomes of larynx cancer-specific survival (CSS), overall survival (OS), and non-larynx cancer survival (NCS) were evaluated in multivariable Cox and Fine-Gray models. RESULTS: In 1047 patients, the optimal pretreatment NLR cutoff was identified as 4.17 - 722 patients with NLR ⩽ 4.17, 325 patients with NLR > 4.17. The elevated NLR cohort had a higher proportion of T4 disease (39.4% vs 28.4%), node positive disease (52.3% vs 43.1%), and surgical treatment (43.7% vs 35.2%). In multivariable analysis, NLR > 4.17 was independently associated with worse OS (HR 1.31, 95% CI 1.12-1.54, P = .001) and worse CSS (HR 1.46, 95% CI 1.17-1.83, P < .001), but not with NCS (HR 0.94, 95% CI 0.75-1.18, P = .58). CONCLUSION: In locoregionally advanced larynx cancer treated with curative intent, we identified elevated NLR to be associated with inferior OS and CSS. Further prospective studies are needed to investigate pretreatment NLR and our identified 4.17 cutoff as a potential larynx cancer-specific marker for this high risk population.

Evaluating the clinical trends and benefits of low-dose computed tomography in lung cancer patients.

BACKGROUND: Despite guideline recommendations, utilization of low-dose computed tomography (LDCT) for lung cancer screening remains low. The driving factors behind these low rates and the real-world effect of LDCT utilization on lung cancer outcomes remain limited. METHODS: We identified patients diagnosed with non-small cell lung cancer (NSCLC) from 2015 to 2017 within the Veterans Health Administration. Multivariable logistic regression assessed the influence of LDCT screening on stage at diagnosis. Lead time correction using published LDCT lead times was performed. Cancer-specific mortality (CSM) was evaluated using Fine-Gray regression with non-cancer death as a competing risk. A lasso machine learning model identified important predictors for receiving LDCT screening. RESULTS: Among 4664 patients, mean age was 67.8 with 58-month median follow-up, 95% CI = [7-71], and 118 patients received ≥1 screening LDCT before NSCLC diagnosis. From 2015 to 2017, LDCT screening increased (0.1%-6.6%, mean = 1.3%). Compared with no screening, patients with ≥1 LDCT were more than twice as likely to present with stage I disease at diagnosis (odds ratio [OR] 2.16 [95% CI 1.46-3.20]) and less than half as likely to present with stage IV (OR 0.38 [CI 0.21-0.70]). Screened patients had lower risk of CSM even after adjusting for LDCT lead time (subdistribution hazard ratio 0.60 [CI 0.42-0.85]). The machine learning model achieved an area under curve of 0.87 and identified diagnosis year and region as the most important predictors for receiving LDCT. White, non-Hispanic patients were more likely to receive LDCT screening, whereas minority, older, female, and unemployed patients were less likely. CONCLUSIONS: Utilization of LDCT screening is increasing, although remains low. Consistent with randomized data, LDCT-screened patients were diagnosed at earlier stages and had lower CSM. LDCT availability appeared to be the main predictor of utilization. Providing access to more patients, including those in diverse racial and socioeconomic groups, should be a priority.

Salvage Following Transoral Laser Microsurgery for Early Glottic Cancer in National Veteran Database.

OBJECTIVES: Transoral laser microsurgery (TLM) is commonly utilized for early glottic cancer and offers favorable oncologic and functional outcomes. However, the survival implications of salvage therapy for recurrent or persistent disease have not been definitively characterized. STUDY DESIGN: Retrospective, national database cohort study. METHODS: Data were extracted from Veterans Health Affairs (VHA) Informatics and Computing Infrastructure (VINCI) concerning the TLM-based management of T1-T2 glottic squamous cell carcinoma patients between 2000 and 2017. Patients were characterized as either requiring TLM-only, or in cases of persistent or recurrent local disease, TLM plus change in treatment modality (radiotherapy, chemoradiotherapy, or open surgery). Predictors of overall survival (OS), cancer-specific survival (CSS), and salvage-free survival were evaluated via Cox and Fine-Gray models. RESULTS: About 553 patients (70.9% T1a, 13.4% T1b, 15.7% T2) were included, with a median follow-up time of 74.5 months. The need for non-TLM salvage increased along with more advanced disease (11.7% T1a, 29.7% T1b, 32.2% T2). Compared to patients with T1a disease, those with T1b and T2 tumors initially treated with TLM had a significantly higher probability of receiving non-TLM salvage (T1b: HR 2.70, 95% CI: 1.61-4.54; T2: HR 3.02, 95% CI: 1.88-4.84). In a multivariable model, receipt of non-TLM salvage was not a significant predictor of either OS (HR = 0.91, 95% CI: 0.62-1.33, P = .624) or CSS (HR 1.21 95% CI 0.51-2.86, P = .667). CONCLUSION: The majority of patients with early glottic cancer that are managed with TLM do not require additional salvage therapy. When non-TLM salvage was required, there was no decrement in OS or CSS. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2766-2772, 2021.

Association of race and health care system with disease stage and survival in veterans with larynx cancer.

BACKGROUND: Black patients with laryngeal squamous cell carcinoma (LSCC) historically have inferior outcomes in comparison with White patients. The authors investigated these racial disparities within the Veterans Health Administration (VHA), an equal-access system, and within the Surveillance, Epidemiology, and End Results (SEER) program, which is representative of the US hybrid-payer system. METHODS: Patients with invasive (T1 or greater) LSCC were included from SEER (2004-2015) and the VHA (2000-2017). The primary outcomes of overall survival (OS) and larynx cancer-specific survival (LCS) were evaluated in Cox and Fine-Gray models. RESULTS: In the SEER cohort (7122 patients: 82.6% White and 17.4% Black), Black patients were more likely to present with advanced disease and had inferior OS (hazard ratio [HR], 1.37; 95% CI, 1.26-1.50; P < .0001) in a multivariable analysis. Black LCS was worse in a univariable analysis (HR, 1.42; 95% CI, 1.27-1.58; P < .0001), but this effect was attenuated by 83% when the authors controlled for the TNM category and was found to be insignificant in a multivariable analysis (HR, 1.05; 95% CI, 0.93-1.18; P = .42). In the VHA cohort (9248 patients: 79.7% White and 20.3% Black), the 2 racial cohorts presented with similar tumor characteristics and similar OS (HR, 0.95; 95% CI, 0.89-1.02; P = .14). Black LCS was similar in univariable (HR, 1.10; 95% CI, 1.00-1.22; P = .05) and multivariable analyses (HR, 1.02; 95% CI, 0.92-1.14; P = .67). CONCLUSIONS: Black patients with LSCC had a tumor burden at diagnosis and survival outcomes comparable to those of White patients within the VHA; this was counter to what was observed in the SEER analysis and prior national trends. This study's findings point toward the notable role of health care access in contributing to racial health disparities in the realm of larynx cancer.

Clinical Data Prediction Model to Identify Patients With Early-Stage Pancreatic Cancer.

PURPOSE: Pancreatic cancer is an aggressive malignancy with patients often experiencing nonspecific symptoms before diagnosis. This study evaluates a machine learning approach to help identify patients with early-stage pancreatic cancer from clinical data within electronic health records (EHRs). MATERIALS AND METHODS: From the Optum deidentified EHR data set, we identified early-stage (n = 3,322) and late-stage (n = 25,908) pancreatic cancer cases over 40 years of age diagnosed between 2009 and 2017. Patients with early-stage pancreatic cancer were matched to noncancer controls (1:16 match). We constructed a prediction model using eXtreme Gradient Boosting (XGBoost) to identify early-stage patients on the basis of 18,220 features within the EHR including diagnoses, procedures, information within clinical notes, and medications. Model accuracy was assessed with sensitivity, specificity, positive predictive value, and the area under the curve. RESULTS: The final predictive model included 582 predictive features from the EHR, including 248 (42.5%) physician note elements, 146 (25.0%) procedure codes, 91 (15.6%) diagnosis codes, 89 (15.3%) medications, and 9 (1.5%) demographic features. The final model area under the curve was 0.84. Choosing a model cut point with a sensitivity of 60% and specificity of 90% would enable early detection of 58% late-stage patients with a median of 24 months before their actual diagnosis. CONCLUSION: Prediction models using EHR data show promise in the early detection of pancreatic cancer. Although widespread use of this approach on an unselected population would produce high rates of false-positive tests, this technique may be rapidly impactful if deployed among high-risk patients or paired with other imaging or biomarker screening tools.

Palliative Radiotherapy Versus Esophageal Stent Placement in the Management of Patients With Metastatic Esophageal Cancer.

BACKGROUND: Patients with advanced esophageal cancer often experience pain and dysphagia, yet the optimal palliative management remains unclear. This retrospective study evaluated outcomes and adverse effects of palliative radiotherapy (RT) compared with esophageal stenting among a cohort of U.S. veterans with metastatic esophageal cancer. PATIENTS AND METHODS: We identified 1,957 veterans in the United States with metastatic esophageal cancer who received palliative RT to the esophagus or esophageal stenting, and assessed the risks of severe adverse effects, including esophageal fistula formation, perforation, obstruction, hemorrhage, and esophagitis. We determined palliative efficacy by evaluating pain and dysphagia scores before and after intervention. Multivariable analyses were used to control for potential confounding factors. RESULTS: In our cohort, 1,593 patients underwent RT and 364 underwent esophageal stenting. The cumulative incidence of any severe adverse effect at 6 months was higher among patients who received stents compared with those who received RT (21.7% vs 12.4%; P<.0010). In multivariable analysis, patients who received stents had an increased risk of any severe adverse effect, including fistula, perforation, and hemorrhage (all P<.0500). Multivariable analysis also showed that, compared with stenting, RT was associated with more rapid and durable pain relief (P<.0010) with no difference in relief of dysphagia over time when accounting for pretreatment dysphagia scores (P=.1029). CONCLUSIONS: Compared with esophageal stenting, RT was associated with a decreased risk of adverse effects, greater pain relief, and equivalent relief of moderate to severe dysphagia over time. Unmeasured patient- or tumor-related factors could have influenced the choice of intervention, thereby impacting our study outcomes. To our knowledge, this is the largest study to date analyzing the comparative risks and benefits of palliative RT and esophageal stenting among patients with metastatic esophageal cancer.