Guideline-concordant Treatment Research Articles

The Relative Survival Impact of Guideline-Concordant Clinical Staging and Stage-Appropriate Treatment of Potentially Curable Non-Small Cell Lung Cancer

Lung cancer management guidelines strive to improve outcomes. Theoretically, thorough staging promotes optimal treatment selection. We examined the association between guideline-concordant invasive mediastinal nodal staging, guideline-concordant treatment, and non-small cell lung cancer survival. What is the current practice of invasive mediastinal nodal staging for patients with lung cancer in a structured multidisciplinary care environment? Is guideline-concordant staging associated with guideline-concordant treatment? How do they relate to survival? We evaluated patients with nonmetastatic non-small cell lung cancer diagnosed from 2014 through 2019 in the Multidisciplinary Thoracic Oncology Program of the Baptist Cancer Center, Memphis, Tennessee. We examined patterns of mediastinal nodal staging and stage-stratified treatment, grouping patients into cohorts with guideline-concordant staging alone, guideline-concordant treatment alone, both, or neither. We evaluated overall survival with Kaplan-Meier curves and Cox proportional hazards models. Of 882 patients, 456 (52%) received any invasive mediastinal staging. Seventy-four percent received guideline-concordant staging; guideline-discordant staging decreased from 34%in 2014 to 18%in 2019 (P< .0001). Recipients of guideline-concordant staging were more likely to receive guideline-concordant treatment (83%vs66%; P< .0001). Sixty-one percent received both guideline-concordant invasive mediastinal staging and guideline-concordant treatment; 13%received guideline-concordant staging alone; 17%received guideline-concordant treatment alone; and 9%received neither. Survival was greatest in patients who received both (adjusted hazard ratio [aHR], 0.41; 95%CI, 0.26-0.63), followed by those who received guideline-concordant treatment alone (aHR, 0.60; 95%CI, 0.36-0.99), and those who received guideline-concordant staging alone (aHR, 0.64; 95%CI, 0.37-1.09) compared with neither (P< .0001, log-rank test). Levels of guideline-concordant staging were high, were rising, and were associated with guideline-concordant treatment selection in this multidisciplinary care cohort. Guideline-concordant staging and guideline-concordant treatment were complementary in their association with improved survival, supporting the connection between these two processes and lung cancer outcomes.

Abstract PO-191: Contributions of tumor characteristics, treatment, and access to care factors on racial disparities in endometrial cancer survival

Abstract Background: Among women with endometrial cancer (EC), well-established mortality disparities between White and Black women have continued to widen over time. Hispanic, American Indian/Alaska Native (AI/AN) women, and women broadly categorized as Asian or Pacific Islander have not been the focus of many prior studies of racial disparities in EC survival. We examined racial disparities in survival and assessed the contributions of demographic, tumor, treatment, access to care, and health status factors on racial disparities in survival among women with EC. Methods: Participants were diagnosed between 2004 and 2015 with stages 1A through 4B, endometroid and non-endometroid EC in the National Cancer Database (NCDB). Race was categorized as non-Hispanic white (NHW), non-Hispanic black (NHB), Hispanic, Asian, Native-Hawaiian/Pacific Islander (NH/PI), and AI/AN. We used a series of Cox regression models to estimate the relative contribution of prognostic factors to excess risk of mortality. We examined the following classes of prognostic factors: age at diagnosis, tumor characteristics (stage and histology), guideline-concordant treatment, access to care (insurance status, facility type, treatment delay), and Charlson comorbidity. Each class of factors was added individually to a baseline race-only model, and we estimated the percentage contribution of each class on changes in the hazard ratio (HR) for race using the equation: (HR0 – HRn)/(HR0 – 1), in which HR0 is from the race-only model and HRn is the HR for race categories from the model with the variables of interest. Asian women comprised the reference category in all models as mortality was lowest in this group. Changes in HRs are described as percentages. Results: Our study population included 208,112 women with EC. In the race-only model, overall HRs relative to Asians were 2.49 (95% CI, 2.32-2.67), 1.41 (95% CI, 1.18-1.69), 1.29 (95% CI, 1.20-1.38), 1.18 (95% CI, 0.97-1.43), and 1.09 (95% CI, 1.01-1.18) for NHB, NH/PI, NHW, AI/AN, and Hispanic women, respectively. Age at diagnosis was the most influential variable among NHW and NH/PI women, describing 93.1% and 75.6% of the survival disparity, respectively. Tumor characteristics were the most influential contributor for NHB women (40.9%), while among Hispanic and AI/AN women, access to care (77.8%) and comorbidities (50%) were responsible for the largest attenuation in HRs, respectively. Guideline-concordant treatment was linked with a small attenuation in HRs among NHB (2.7%), NHW (3.4%), and NH/PI (7.3%). Conclusions: Contributors to racial disparities in EC survival vary by race/ethnicity. Some factors, like age, are non-modifiable and represent poor intervention targets. Conversely, other factors, like high stage, comorbidities, and low access to care, are challenging but modifiable problems that implicate the larger societal context. Our preliminary findings suggest that interventions for reducing EC survival disparities will require a tailored approach for the particular group of women for whom we are trying to intervene. Citation Format: Jordyn A. Brown, Jennifer A. Sinnott, Kemi M. Doll, Macarius M. Donneyong, Tasleem J. Padamsee, Elyse Llamocca, David E. Cohn, Casey Cosgrove, Ashley S. Felix. Contributions of tumor characteristics, treatment, and access to care factors on racial disparities in endometrial cancer survival [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-191.

Sputum Proteomics in Nontuberculous Mycobacterial Lung Disease

Nontuberculous mycobacterial (NTM) infections are difficult to diagnose and treat. Biomarkers to identify patients with active infection or at risk of disease progression would have clinical utility. Sputum is the most frequently used matrix for the diagnosis of NTM lung disease. Can sputum proteomics be used to identify NTM-associated inflammatory profiles in sputum? Patients with NTM lung disease and a matched cohort of patients with COPD, bronchiectasis (BE), and cystic fibrosis (CF) without NTM lung disease were enrolled from two hospitals in the United Kingdom. Liquid chromatography-tandem mass spectrometry was used to identify proteomic biomarkers associated with underlying diagnosis (COPD, BE, and CF), the presence of NTM lung disease defined according to American Thoracic Society/Infectious Diseases Society of America criteria, and severity of NTM. A subset of patients receiving guideline-concordant NTM treatment were studied to identify protein changes associated with treatment response. This study analyzed 95 sputum samples from 55 subjects (BE, n= 21; COPD, n= 19; CF, n= 15). Underlying disease and infection with Pseudomonas aeruginosa were the strongest drivers of sputum protein profiles. Comparing protein abundance in COPD, BE, and CF found that 12 proteins were upregulated in CF compared with COPD, including MPO, AZU1, CTSG, CAT, and RNASE3, with 21 proteins downregulated, including SCGB1A1, IGFBP2, SFTPB, GC, and CFD. Across CF, BE, and COPD, NTM infection (n= 15) was not associated with statistically significant differences in sputum protein profiles compared with those without NTM. Two proteins associated with iron chelation were significantly downregulated in severe NTM disease. NTM treatment was associated with heterogeneous changes in the sputum protein profile. Patients with NTM and a decrease in immune response proteins had a subjective symptomatic improvement. Sputum proteomics identified candidate biomarkers of NTM severity and treatment response. However, underlying lung disease and typical bacterial pathogens such as P aeruginosa are also key determinants of the sputum proteomic profile.

Practice patterns and real-life outcomes for patients with acute promyelocytic leukemia in the United States

Acute promyelocytic leukemia (APL) is associated with a favorable long-term prognosis if appropriate treatment is initiated promptly. Outcomes in clinical trials and population-based registries vary; potential explanations include a delay in treatment and lower adherence to guideline-recommended therapy in real-world practice. We used the Vizient Clinical Data Base to describe demographic characteristics, baseline clinical characteristics, and treatment patterns in patients newly diagnosed with APL during the study period of April 2017 to March 2020. Baseline white blood cell count was used to assign risk status and assess treatment concordance with National Comprehensive Cancer Network guidelines. Logistic regression models examined adjusted associations between patient, hospital, disease characteristics, and adverse outcomes (in-hospital death or discharge to hospice). Among 1464 patients with APL, 205 (14.0%) experienced an adverse outcome. A substantial subset (20.6%) of patients did not receive guideline-concordant regimens. Odds of adverse outcomes increased with failure to receive guideline-concordant treatment (odds ratio [OR], 2.31; 95% confidence interval [CI], 1.43-3.75; P = .001), high-risk disease (OR, 2.48; 95% CI, 1.53-4.00; P < .001), and increasing age (≥60 years: OR, 11.13; 95% CI, 4.55-27.22; P < .001). Higher hospital acute myeloid leukemia (AML) patient volume was associated with lower odds of adverse outcome (OR, 0.44; 95% CI, 0.20-0.99 [for ≤50 vs >200 AML patients per year]; P = .046). In conclusion, in this large database analysis, 14.0% of patients newly diagnosed with APL died or were discharged to hospice. A substantial proportion of patients did not receive guideline-concordant therapy, potentially contributing to adverse outcomes.

MA15.05 Rates of Guideline-Concordant Surgery and Adjuvant Chemotherapy Among Patients in The U.S. ALCHEMIST Study (Alliance)

The standard of care for resectable non-small cell lung cancer (NSCLC) includes anatomic surgical resection with adequate lymph node dissection and adjuvant chemotherapy for appropriate patients. Historically, many patients with early-stage NSCLC have not received such guideline-concordant therapy. Longstanding disparities have also existed in the delivery of quality cancer care by sociodemographic factors such as race and ethnicity. This could impact interpretation of adjuvant therapy trials. In this descriptive analysis, we examined rates of guideline-concordant treatment among patients enrolled in ALCHEMIST, a large U.S.-wide screening trial to facilitate enrollment to targeted adjuvant treatment trials for resectable NSCLC, enrolling at 754 sites. Patients who enrolled in ALCHEMIST (Alliance A151216) from August 18, 2014-April 1, 2019 who did not enroll in a therapeutic adjuvant therapy clinical trial were included; these patients had stage IB-IIIA disease (AJCC 7th edition), with tumors at least 4 cm in size and/or positive lymph nodes. Four outcomes are reported: whether patients (1) had adequate lymph node dissection per National Comprehensive Cancer Network criteria (≥ one N1 nodal station plus ≥ three N2 nodal stations); (2) received any adjuvant chemotherapy; (3) received any cisplatin-based adjuvant chemotherapy; and (4) received at least 4 cycles of adjuvant chemotherapy. Associations between these binary outcomes and sociodemographic variables were explored using unadjusted modified Poisson regression models accounting for trial site-level correlation. 2,834 patients were analyzed; 53.4% had adequate lymph node dissection; 57.1% received any adjuvant chemotherapy; 34.1% received any cisplatin-based adjuvant chemotherapy; and 43.7% received at least four cycles of adjuvant platinum-based chemotherapy. The distribution of treatment by key clinical and demographic characteristics is provided in Table 1; adjuvant chemotherapy was delivered more often to patients who were younger, had more advanced stage, had non-squamous NSCLC, and did not have EGFR-mutant tumors. Rates were similar across categories of race and ethnicity. Many patients with early-stage NSCLC did not receive adequate lymph node dissection or adjuvant chemotherapy despite indications for such treatment, even among patients who consented for testing to inform eligibility for an adjuvant therapy clinical trial. No substantial disparities in treatment were observed by race or ethnicity in this clinical trial cohort, contrary to historical patterns in population-based cohorts. Efforts are needed to optimize utilization of therapies with proven benefit for early-stage NSCLC. These results may inform the generalizability of clinical trials of novel therapies in the adjuvant setting. Support: U10CA180821, U10CA180882; U10CA180820 (ECOG-ACRIN); https://acknowledgments.alliancefound.org; Clinicaltrials.gov Identifier: NCT02194738

Efficacy and validity of guideline-concordant treatment according to the JRS guidelines for the managements of pneumonia in adults updated in 2017 for nursing and healthcare-associated pneumonia. A propensity-matching score analysis

IntroductionPatients with nursing and healthcare-associated pneumonia (NHCAP) commonly receive empiric antibiotic therapy according to the guideline's recommendation corresponding to the patient's deteriorated conditions. However, it is unclear whether guideline-concordant treatment (GCT) could be effective or not. Patients and methodsTo evaluate the efficacy and validity of GCT according to the current guideline for pneumonia, we conducted this retrospective study. NHCAP patients who were admitted to our institute between 2014 and 2017 were enrolled. Based on the initial antibiotic treatment, these patients were divided into two groups, the GCT group (n = 83) and the non-GCT group (n = 146). Propensity score matching (PSM) was used to balance the baseline characteristics and potential confounders between the two groups. After PSM, patients’ characteristics, microbial profiles, and clinical outcomes were evaluated. ResultsBoth groups were well-balanced after PSM, and 78 patients were selected from each group. There were no differences in patients’ characteristics or microbial profiles between the two groups. As for outcomes, there were no differences in 30-day, in-hospital mortality rate, duration of antibiotic treatment, or admission. The severity of pneumonia was more severe in patients with the GCT group than those with the non-GCT group. Anti-pseudomonal agents as initial treatment were more frequently seen in patients with the GCT group than those in the non-GCT group. ConclusionUnlike previous studies, GCT's recommendation for management of pneumonia by the JRS in 2017 would appear to be valid and does not increase the mortality rate.

The impact of delayed surgical treatment of suspected stage I ovarian cancer: lessons for a pandemic

Objectives: During the COVID-19 pandemic, the Society of Gynecologic Oncology and other medical societies provided guidelines about acceptable delays in oncologic treatments for patients with a suspected malignancy. The objective of this study was to characterize the association between timing of treatment and survival and to evaluate how extended delays to guideline-concordant treatment for suspected stage I high grade serous ovarian cancer might impact survival. Methods: Using the National Cancer Data Base (2004-2015), patients surgically treated for clinical stage I high grade serous ovarian cancer were identified. Patients receiving surgery within 14 days of diagnosis were compared to those receiving surgery 2-4 months after diagnosis. The groups were propensity matched with 2:1 matching to balance baseline characteristics. Survival outcomes of the two cohorts were assessed using Kaplan-Meier analysis, the log-rank test, and multivariable Cox proportional hazards analysis. Results: During the study period, 10,957 patients underwent guideline-concordant surgery for stage I high-grade serous ovarian cancer within 14 days of diagnosis (early) and 171 patients underwent surgery 2-4 months following diagnosis (delayed). Between patients in the early versus delayed treatment groups, the delayed group was more likely to be Black (5.3% vs 11.8%, p=0.003) and have a smaller tumor size (8.0 vs. 6.2 cm, p Download : Download high-res image (81KB) Download : Download full-size image Conclusions: In this national analysis, extended delay of treatment for stage I high grade serous ovarian cancer was associated with similar survival outcomes when compared to timely treatment in pre-match and post-match cohorts. In the setting of the COVID-19 pandemic, where hospital resources may be limited, delays in surgery are concerning and prompt oncologic treatment is preferred; however, at least based on these retrospective data, delays in surgery for presumed stage I ovarian cancer may not be associated with significantly worse survival.

Survival Impact of an Enhanced Multidisciplinary Thoracic Oncology Conference in a Regional Community Health Care System

IntroductionWe compared NSCLC treatment and survival within and outside a multidisciplinary model of care from a large community health care system. MethodsWe implemented a rigorously benchmarked “enhanced” Multidisciplinary Thoracic Oncology Conference (eMTOC) and used Tumor Registry data (2011–2017) to evaluate guideline-concordant care. Because eMTOC was located in metropolitan Memphis, we separated non-MTOC patient by metropolitan and regional location. We categorized National Comprehensive Cancer Network guideline-concordant treatment as “preferred,” or “appropriate” (allowable under certain circumstances). We compared demographic and clinical characteristics across cohorts using chi-square tests and survival using Cox regression, adjusted for multiple testing. We also performed propensity-matched and adjusted survival analyses. ResultsOf 6259 patients, 14% were in eMTOC, 55% metropolitan non-MTOC, and 31% regional non-MTOC cohorts. eMTOC had the highest rates of African Americans (34% versus 28% versus 22%), stages I to IIIB (63 versus 40 versus 50), urban residents (81 versus 78 versus 20), stage-preferred treatment (66 versus 57 versus 48), guideline-concordant treatment (78 versus 70 versus 63), and lowest percentage of nontreatment (6 versus 21 versus 28); all p values were less than 0.001. Compared with eMTOC, hazard for death was higher in metropolitan (1.5, 95% confidence interval: 1.4–1.7) and regional (1.7, 1.5–1.9) non-MTOC; hazards were higher in regional non-MTOC versus metropolitan (1.1, 1.0–1.2); all p values were less than 0.05 after adjustment. Results were generally similar after propensity analysis with and without adjusting for guideline-concordant treatment. ConclusionsMultidisciplinary NSCLC care planning was associated with significantly higher rates of guideline-concordant care and survival, providing evidence for rigorous implementation of this model of care.

Comparison of Multimodal Therapies and Outcomes Among Patients With High-Risk Prostate Cancer With Adverse Clinicopathologic Features

The optimal management strategy for high-risk prostate cancer and additional adverse clinicopathologic features remains unknown. To compare clinical outcomes among patients with high-risk prostate cancer after definitive treatment. This retrospective cohort study included patients with high-risk prostate cancer (as defined by the National Comprehensive Cancer Network [NCCN]) and at least 1 adverse clinicopathologic feature (defined as any primary Gleason pattern 5 on biopsy, clinical T3b-4 disease, ≥50% cores with biopsy results positive for prostate cancer, or NCCN ≥2 high-risk features) treated between 2000 and 2014 at 16 tertiary centers. Data were analyzed in November 2020. Radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy (ADT), or EBRT plus brachytherapy boost (BT) with ADT. Guideline-concordant multimodal treatment was defined as RP with appropriate use of multimodal therapy (optimal RP), EBRT with at least 2 years of ADT (optimal EBRT), or EBRT with BT with at least 1 year ADT (optimal EBRT with BT). The primary outcome was prostate cancer-specific mortality; distant metastasis was a secondary outcome. Differences were evaluated using inverse probability of treatment weight-adjusted Fine-Gray competing risk regression models. A total of 6004 men (median [interquartile range] age, 66.4 [60.9-71.8] years) with high-risk prostate cancer were analyzed, including 3175 patients (52.9%) who underwent RP, 1830 patients (30.5%) who underwent EBRT alone, and 999 patients (16.6%) who underwent EBRT with BT. Compared with RP, treatment with EBRT with BT (subdistribution hazard ratio [sHR] 0.78, [95% CI, 0.63-0.97]; P = .03) or with EBRT alone (sHR, 0.70 [95% CI, 0.53-0.92]; P = .01) was associated with significantly improved prostate cancer-specific mortality; there was no difference in prostate cancer-specific mortality between EBRT with BT and EBRT alone (sHR, 0.89 [95% CI, 0.67-1.18]; P = .43). No significant differences in prostate cancer-specific mortality were found across treatment cohorts among 2940 patients who received guideline-concordant multimodality treatment (eg, optimal EBRT alone vs optimal RP: sHR, 0.76 [95% CI, 0.52-1.09]; P = .14). However, treatment with EBRT alone or EBRT with BT was consistently associated with lower rates of distant metastasis compared with treatment with RP (eg, EBRT vs RP: sHR, 0.50 [95% CI, 0.44-0.58]; P < .001). These findings suggest that among patients with high-risk prostate cancer and additional unfavorable clinicopathologic features receiving guideline-concordant multimodal therapy, prostate cancer-specific mortality outcomes were equivalent among those treated with RP, EBRT, and EBRT with BT, although distant metastasis outcomes were more favorable among patients treated with EBRT and EBRT with BT. Optimal multimodality treatment is critical for improving outcomes in patients with high-risk prostate cancer.

The impact of socioeconomic status on survival in stage III colon cancer patients: A retrospective cohort study using the SEER census-tract dataset.

BackgroundThe impact of socioeconomic status (SES) has been described for screening and accessing treatment for colon cancer. However, little is known about the “downstream” effect in patients who receive guideline‐concordant treatment. This study assessed the impact of SES on cancer‐specific survival (CSS) and overall survival (OS) for stage III colon cancer patients.MethodsThe SEER Census Tract‐Level SES Dataset from 2004 to 2015 was used to identify stage III colon adenocarcinoma patients who received curative‐intent surgery and adjuvant chemotherapy. The predictor variable was census tract SES. SES was analyzed as quintiles. The outcome variables were OR and CSS. Statistical analysis included chi square tests for association, Kaplan–Meier, Cox, Fine and Gray regression for survival analysis.ResultsIn total, 27,222 patients met inclusion criteria. Lower SES was associated with younger age, Black or Hispanic race/ethnicity, Medicaid/uninsured, higher T stage, and lower grade tumors. CSS at the 25th percentile was 54 months for the lowest SES quintile and 80 for the highest. Median OS was 113 months for the lowest SES quintile and not reached for highest. The 5‐year CSS rate was 72.4% for the lowest SES quintile compared to 78.9% in the highest (p < 0.001). The 5‐year OS rate was 66.5% for the lowest SES quintile and 74.6% in the highest (p < 0.001).ConclusionThis is the first study to evaluate CSS and OS in an incidence‐based cohort of stage III colon cancer patients using a granular, standardized measure of SES. Despite receipt of guideline‐based treatment, SES was associated with disparities in CSS and OS.

Association of guideline-concordant initial systemic treatment with clinical and economic outcomes among older women with metastatic breast cancer in the United States

PurposeWe examined guideline-concordant initial systemic treatment among women with metastatic breast cancer, its predictors, and if guideline-concordant treatment was associated with mortality, healthcare utilization and Medicare expenditures. MethodsThis retrospective observational cohort study was conducted using the Surveillance, Epidemiology, End Results-Medicare linked database. Women aged 66–90 years diagnosed with metastatic breast cancer during 2010–2013 (N = 1282) were included. The National Comprehensive Cancer Network treatment guidelines were used to determine the guideline-concordant initial systemic treatment following cancer diagnosis. A logistic regression analysis was conducted to examine significant predictors of guideline-concordant treatment. Generalized linear regressions were used to examine the association between guideline-concordant treatment and healthcare utilization and average monthly Medicare expenditures. ResultsAbout 74% of the study cohort received guideline-concordant initial systemic treatment. Women who received guideline-concordant treatment were significantly more likely to be comparatively younger (p < 0.05), were married/partnered (p = 0.0038), had HER2 positive tumors, and had good performance status. Adjusted hazards ratios for all-cause (2.364, p < 0.0001) and breast-cancer specific mortality (2.179, p < 0.0001) were higher for women who did not receive guideline-concordant treatment. Rates of healthcare utilization were also higher for women not receiving guideline-concordant treatment. Average monthly Medicare expenditures were 100.4% higher (95% confidence interval: $77.3%–126.5%) for women who did not receive guideline-concordant treatment compared to those who received guideline-concordant treatment (p < 0.0001). ConclusionOne fourth of the study cohort did not receive guideline-concordant initial systemic treatment. Guideline-concordant initial treatment was associated with reduced mortality, and lower healthcare utilization and Medicare expenditures in women with metastatic breast cancer.

PCN147 Impact of Guideline-Concordant Treatment on Survival Among Older Women with Advanced Ovarian Cancer

We examined the impact of adherence to the National Comprehensive Cancer Network (NCCN) treatment guidelines among women with advanced-stage ovarian cancer on overall survival. A retrospective observational cohort study was conducted using Surveillance, Epidemiology, and End Results (SEER) – Medicare linked database. Women aged 66 to 90 years who were diagnosed with stage II or higher epithelial ovarian cancer during 2011-2015 were included. Guideline-concordant primary cancer treatment was defined as receipt of both surgery and chemotherapy per the NCCN guidelines. Kaplan-Meier analysis was used to compare overall survival rates. Multivariable Cox proportional hazards model was used to identify if receipt of guideline-concordant treatment impacted overall survival Out of a total of 3,276 patients with ovarian cancer who met inclusion criteria, 56.6% received guideline-concordant treatment. The median survival time for women who received guideline-concordant treatment was 36.1 months (95% Confidence Interval (CI): 33.8-39.5 months) compared with 12.5 months for non-guideline concordant treatment (95%CI:11.6-13.5 months) group. In the Cox regression model, women who did not receive guideline-concordant treatment had higher hazards of dying from any cause when compared with women who received guideline-concordant treatment (Adjusted Hazards Ratio (AHR): 2.766; p < 0.0001). Receipt of non-guideline concordant cancer treatment is associated with poorer survival among elderly women with advanced ovarian cancer. Adoption of optimal treatment strategies (both surgery and chemotherapy) is crucial for improved survival rates in this vulnerable group.

PCN149 Guideline-Concordant Cancer Treatment Among Older Women with Advanced Ovarian Cancer: A SEER-Medicare Analysis

We determined adherence to the National Comprehensive Cancer Network (NCCN) cancer treatment guidelines among older women with advanced epithelial ovarian cancer and identified significant predictors of guideline-concordant treatment.

National Utilization of Imatinib in the Management of Resected Gastrointestinal Stromal Tumors.

Imatinib decreases recurrence risk and improves overall survival (OS) in localized gastrointestinal stromal tumors (GISTs); however, the extent to which patients receive appropriate treatment in the US has not been well characterized. Patients with non-metastatic, resectable GIST were included in this study (National Cancer Database, 2010-2015). Those with a low-risk of recurrence were classified as receiving overtreatment or guideline-concordant treatment, while those with a high-risk of recurrence were classified as receiving undertreatment or guideline-concordant treatment. Multivariable logistic regression was used to determine factors associated with non-concordant treatment. The association between non-concordant treatment and OS was evaluated using multivariable Cox regression and propensity score matching. Among 3088 patients with high-risk GIST, 41% were undertreated, and among 3908 patients with low-risk GIST, 18.8% were overtreated. For patients with high-risk GIST, age >60years, African American race, and treatment at a community or comprehensive cancer program were associated with undertreatment. Among low-risk patients, small bowel primary, tumor size >2cm, and tumors with >1 mitotic figure per 50 high-power fields were more likely to be overtreated. After propensity score matching, guideline-concordant therapy was associated with an 8.8% improvement in 5-year OS (81.9% vs. 73.1%, p=0.002) for those with high-risk GIST and decreased risk of death (hazard ratio 0.63, 95% confidence interval 0.47-0.84). There was no statistically significant difference in survival for patients with low-risk GIST with the addition of imatinib overtreatment (overtreatment 93.9% vs. 89.6%, p=0.053). Nearly 30% of GIST patients do not receive guideline-concordant treatment and future work is needed to understand the factors driving non-concordant treatment.

Prospective cohort of real-world, curative-intent breast cancer treatment patterns in Malawi.

e18736 Background: Despite increasing availability of curative-intent breast cancer treatment in concordance with the National Comprehensive Cancer Network (NCCN) Harmonized Guidelines for Sub-Saharan Africa (SSA), few descriptions of their application in SSA are available. Our aim was to describe patterns of curative-intent treatment including neoadjuvant (NAC) and/or adjuvant chemotherapy (AdC) and surgery (S) by stage and HIV status, and the association between guideline-concordant treatment completion and overall survival (OS). Methods: We enrolled newly diagnosed breast cancer patients in a prospective cohort study at Kamuzu Central Hospital in Malawi from Dec 2016 – Oct 2018. Unadjusted odds ratios (OR) with 95% CI were calculated to identify factors associated with completion of guideline-concordant treatment, defined as S and at least 4 cycles of NAC or AdC. A logistic regression model was performed using variables with p&lt;0.1. Survival analysis was performed with Kaplan Meier methods and log-rank test. Results: 67 non-metastatic patients were included. 12 (18%) were HIV+; 13 (19%) were Stage II and 54 (81%) Stage III. 46 (69%) began treatment with NAC, of which 39 (85%) were Stage III and 7 (15%) Stage II. 12 (18%) began treatment with S+AdC, of which 5 (42%) were Stage II and 7 (58%) were Stage III. 2 (3%) Stage III patients were treated with palliative chemotherapy (PC). 7 (10%) never received treatment. Overall, 41 (61%) underwent S. In bivariate analysis, factors associated with failure to complete treatment were HIV+ (OR 0.25 CI (0.06-0.99), Stage III (OR 0.10 CI (0.01-0.89) and ER/PR-/HER2+ (OR 0.07 CI (0.01-0.49). In adjusted analysis, ER/PR-/HER2+ (OR 0.12 (0.01-0.97) was associated with failure to complete treatment. HIV+ patients received less NAC than HIV- (2.5 vs 4 cycles; p=0.07) and similar AdC as HIV- (6 vs 6 cycles; p=0.7). Median OS for those who began treatment with NAC was shorter than with S+AdC (28.5 vs 40 months; p=0.01). Median OS for HIV+ vs HIV- who received NAC was 19.7 vs 32.7 months (p=0.10) and received S+AdC was unreached vs 37.1 months (p=0.27). Conclusions: When applying NCCN Harmonized Guidelines for SSA to Malawi, most patients received NAC for curative breast cancer treatment and had significantly shorter OS compared to those receiving upfront S+AdC. Stage III, HIV+, and ER/PR-/HER2+ patients were less likely to complete guideline-concordant treatment which may reflect advanced disease or poor treatment tolerability. Further study is needed to identify barriers to guideline-concordant treatment and inform interventions to improve breast cancer treatment outcomes in Malawi and SSA.[Table: see text]

Patients with early-stage (T1-2N0) adenosquamous lung cancer have worse long-term survival compared to patients with early-stage lung adenocarcinoma or squamous cell histology.

8550 Background: Survival outcomes for patients with adenosquamous carcinoma of the lung are not well understood by virtue of reduced prevalence. The objective of this study is to compare the long-term survival among patients with adenocarcinoma, squamous cell carcinoma and adenosquamous carcinoma of the lung. Methods: Overall survival of all patients with adenosquamous carcinoma, squamous cell carcinoma, and adenocarcinoma who received guideline-concordant treatment for T1-2N0M0 from 2004-2017 in the National Cancer Data Base was assessed using Kaplan-Meier analysis, multivariable Cox proportional hazard analysis, and propensity score-matched analysis. Results: Among patients who met study criteria (N = 88,983), there were 2,469 (2.77%) patients with adenosquamous, 60,148 (67.59%) with adenocarcinoma and 26,366 (29.63%) with squamous cell carcinoma histology. In patients who had T1-T2 N0 M0 disease, adenosquamous carcinoma was associated with significantly worse 5-year overall survival (58.9% [95%CI:56.6%-61.1%]) when compared with adenocarcinoma (72.4% [95% CI:72.0%-72.8%]) and squamous cell carcinoma (62.6% [95% CI:61.9%-63.3%]). In multivariable Cox proportional hazards analysis, adenocarcinoma (HR 0.81 [95% CI:0.76-0.87], p &lt; 0.001) and squamous cell carcinoma (HR 0.86 [95% CI:0.80-0.92], p &lt; 0.001) continued to be associated with significantly better survival when compared to adenosquamous carcinoma histology. A propensity score-matched analysis of 1,854 adenocarcinoma and 1,854 adenosquamous patients who were well matched by 17 common prognostic covariates (including tumor size and comorbidities) found that adenosquamous histology (57.2% [95% CI:54.7%-59.6%]) was associated with worse survival when compared to adenocarcinoma (63.0% [95% CI:60.6%-65.4%]). An additional propensity score-matched analysis of 1,852 squamous cell carcinoma and 1,852 adenosquamous patients matched by the same covariates demonstrated that adenosquamous carcinoma (57.1% [95%CI:54.6%-59.6%]) was associated with worse survival when compared with squamous cell carcinoma (64.0% [95% CI:61.5%-66.4%]). Conclusions: Early stage adenosquamous carcinoma of the lung is associated with worse overall survival compared to its individual histologic components of adenocarcinoma or squamous cell carcinoma. These observations in both the unmatched and propensity matched patient cohorts invoke consideration of multimodality therapy for these early tumors.

Factors associated with appropriate treatment of acute-onset severe obstetrical hypertension

The American College of Obstetricians and Gynecologists recommends that pregnant patients receive expeditious treatment with first-line antihypertensive agents within 1 hour of confirmed severe hypertension to reduce the risk for maternal stroke. However, it is unknown how often this guideline is followed and what factors influence a patient's likelihood of receiving guideline-concordant care. We aimed to identify factors associated with receiving guideline-concordant treatment for an obstetrical hypertensive emergency. We present a case-control study of all pregnant and postpartum patients who had persistent severe hypertension (≥2 systolic blood pressures ≥160 mm Hg or diastolic blood pressure ≥110 mm Hg, or both within 1 hour of each other) during their delivery hospitalization at a tertiary hospital from October 1, 2013, to August 31, 2020. Data were extracted from the hospital electronic medical records using standard definitions and billing and diagnosis codes. We defined receipt of the recommended treatment as administration of a first-line antihypertensive agent (intravenous labetalol, intravenous hydralazine, or immediate-release oral nifedipine) within 60 minutes of the first or second severe-range blood pressure measurement during their delivery hospitalization. Delayed treatment was defined as the administration of a first-line agent >60 minutes after the second elevated blood pressure measurement. Patients were considered untreated if a first-line agent was never administered. Maternal sociodemographic, clinical and pregnancy factors, and time and day of the week of the hypertensive emergency were compared among patients who received the recommended treatment, those who received delayed treatment, and those who were untreated. Bivariate analyses were performed, and multinomial and multivariable logistic regression models were used to adjust for potential confounders. Of the 39,918 deliveries in the cohort, 1987 (5.0%) were complicated by severe, persistent obstetrical hypertension. Of these patients, 532 (26.8%) received the recommended treatment, 356 (17.9%) received delayed treatment, and 1099 (55.3%) did not receive any first-line antihypertensive therapy. The multinomial regression models that were used to compare these 3 groups indicated that patients who received the recommended treatment were more likely to be Black (adjusted odds ratio, 1.85; 95% confidence interval, 1.36-2.51), Hispanic (adjusted odds ratio, 1.77; 95% confidence interval, 1.28-2.52), or pregnant and at <37 weeks of gestation (adjusted odds ratio, 6.65; 95% confidence interval, 5.08-8.72). Treatment was less likely if the severe obstetrical hypertension emergency occurred overnight (7:00 PM to 6:59 AM) (adjusted odds ratio, 0.79; 95% confidence interval, 0.64-0.97) or during the postpartum period (adjusted odds ratio, 0.66; 95% confidence interval, 0.51-0.86). Approximately half of obstetrical patients with at least 2 documented severely elevated blood pressure measurements did not receive the recommended antihypertensive treatment. Of those who did receive treatment, about 40% had delayed treatment. Black and Hispanic race and preterm gestation were associated with an increased likelihood of receiving the recommended treatment when compared with White race and term pregnancies. Patients whose severe obstetrical hypertension emergency occurred overnight and those who were postpartum were less likely to receive any first-line antihypertensive treatment. Overall, patients without sociodemographic and clinical risk factors for severe obstetrical hypertension or other pregnancy complications were less likely to be treated. However, treatment improved significantly over time with the implementation of targeted quality measures and specific institutional policies based on the American College of Obstetricians and Gynecologists' latest severe obstetrical hypertension management guidelines.

The impact of race, comorbid conditions and obesity on survival endpoints in women with high grade endometrial carcinoma

ObjectiveTo estimate overall survival, disease-specific survival, and progression-free survival among high grade endometrial carcinoma cases and to determine factors impacting survival for non-Hispanic white and non-Hispanic black women. MethodsWe identified high grade endometrial carcinoma cases among non-Hispanic white and non-Hispanic black women from ongoing institutional studies, and determined eligibility through medical record and pathologic review. We estimated effects of demographic and clinical variables on survival outcomes using Kaplan Meier methods and Cox proportional hazards modelling. ResultsNon-Hispanic Black women with BMI <25.0 had poorest overall survival compared to non-Hispanic white women with BMI <25.0 (HR 3.03; 95% CI [1.35, 6.81]), followed by non-Hispanic black women with BMI 25.0+ (HR 2.43; 95% CI [1.28, 4.60]). A similar pattern emerged for disease-specific survival. Non-Hispanic black women also had poorer progression-free survival than non-Hispanic white women (HR 1.40; 95% CI [1.01, 1.93]). Other significant factors impacting survival outcomes included receipt of National Cancer Center Network (NCCN) guideline-concordant treatment (GCT), earlier stage at diagnosis, and fewer comorbid conditions. ConclusionsBMI and race interact and modify the association with high grade endometrial carcinoma survival. Other potentially modifiable factors, such as reducing comorbidities and increasing access to GCT will potentially improve survival after diagnosis of high grade endometrial carcinomas. A better understanding of the molecular drivers of these high grade carcinomas may lead to targeted therapies that reduce morbidity and mortality associated with these aggressive tumors.

Differential outcomes of residual disease in surgically-resected non-small cell lung cancer and the importance of guideline-concordant adjuvant therapy.

BackgroundPositive mediastinal lymph nodes, a marker for systemic disease, and positive margins, a marker for local disease, following resection of non-small cell lung cancer (NSCLC) are forms of residual disease. The objective of this study is to compare survival of patients with residual disease and to study the effect of receipt of guideline vs. non-guideline concordant care.MethodsThe National Cancer Database (NCDB) was used to identify patients who underwent treatment naïve surgical resection with clinical stage T1-3N0-1M0 NSCLC between 2006–2016 and had pN2 disease, positive surgical margins, or both. Concordant care was determined based on form of chemotherapy and radiation, dosage, volume, modality, and duration. Kaplan-Meier survival curves and log-rank tests were used to compare five-year survival. Multivariable analysis using Cox proportional hazards modeling identified factors that contributed to worse overall survival.ResultsThere were 8,189 patients included: pN2 (5,416), positive margins (2,386), and both (387). Five-year survival rates for all patients were pN2 (35.8%), positive margins (33.9%), and both (22.9%) (P<0.0001). On multivariable analysis, positive margins were an independent predictor of better survival relative to pN2 disease (HR =0.729, CI: 0.676, 0.787, P<0.0001). Receipt of non-guideline concordant treatment was an independent predictor of worse survival compared to receipt of guideline-concordant treatment (HR =1.61, CI: 1.504, 1.725, P<0.0001).ConclusionsIn upfront surgical patients, guideline-concordant treatment in the setting of residual disease is associated with better overall survival compared with non-guideline concordant treatment. Pathologic N2 disease is associated with a lower survival rate than positive resection margins, possibly reflecting the systemic nature of pN2 disease.

Current prescribing practices and guideline concordance for the treatment of uncomplicated urinary tract infections in women

Uncomplicated urinary tract infections are one of the most common bacterial infections in the United States. Clinical practice guidelines from the Infectious Diseases Society of America recommend nitrofurantoin, trimethoprim-sulfamethoxazole, and Fosfomycin as first-line antibiotic treatments and discourage the use of fluoroquinolone antibiotic agents. US Food and Drug Administration released several black box warnings about fluoroquinolones over the past decade owing to antibiotic resistance and a high burden of adverse events. Historically, uncomplicated urinary tract infections have high rates of guideline-discordant treatment with past studies noting substantial use of fluoroquinolones, directly contradicting clinical practice guidelines. This study aimed to assess the current concordance of physician prescribing practices with Infectious Diseases Society of America guidelines for the treatment of uncomplicated urinary tract infections in women and identify patient and physician predictors of guideline concordance. A retrospective observational secondary analysis was conducted using a series of cross-sectional data extracted from the IQVIA (Plymouth Meeting, Pennsylvania) National Disease and Therapeutic Index from 2015 to 2019. An estimated 44.9 million women with uncomplicated urinary tract infections at the age of 18 to 75 years were treated as outpatients. This population was selected to lack relevant comorbidities or urological abnormalities so that it matched the Infectious Diseases Society of America guidelines. The proportion of prescriptions for each antibiotic drug class were reported with 95% confidence intervals and compared with the Infectious Diseases Society of America guidelines. Patient and physician characteristics were included in a multivariate logistic regression model to identify independent predictors of antibiotic selection and thereby guideline concordance. Of the visits that resulted in antibiotic treatment, the overall concordance rate was 58.4% (26.2 million visits of 44.9 million visits) and increased from 48.2% (3.9 million visits of 8.1 million visits) in 2015 to 64.6% (6.3 million visits of 9.8 million visits) in 2019. The most commonly prescribed antibiotic agents were fluoroquinolones (36.4%, 16.3 million visits of 44.9 million visits), nitrofurantoin (31.8%, 14.3 million visits of 44.9 million visits), and trimethoprim-sulfamethoxazole (26.3%, 11.8 million visits of 44.9 million visits). From 2015 to 2019, fluoroquinolone use decreased whereas nitrofurantoin and beta-lactam use increased. Based on the logistic regression, patients aged 18 to 29 years (odds ratio, 1.60; 95% confidence interval, 1.36-1.88; P<.001) and 30 to 44 years (odds ratio, 1.21; 95% confidence interval, 1.03-1.42; P=.020) had a statistically significantly higher likelihood of receiving guideline-concordant treatment than patients aged 45 to 75 years (reference group). Obstetricians-gynecologists (odds ratio, 3.56; 95% confidence interval, 2.91-4.37; P<.001) and urologists (odds ratio, 3.51; 95% confidence interval, 2.45-5.13; P<.001) had a statistically significantly higher likelihood of concordant treatment than all other specialties combined (reference group). Guideline discordance continues in the treatment of uncomplicated urinary tract infections with the overuse of fluoroquinolones and the underuse of first-line antibiotic agents. Although improving, continued misuse of antibiotic agents may contribute to the growing rates of antibiotic resistance. Actions such as educating physicians about antibiotic resistance and clinical practice guidelines and providing feedback on prescription habits are needed to increase guideline concordance and therefore reduce the use of fluoroquinolones, especially for physicians in family and internal medicine.