Hospital Designations and Their Impact on Guideline-Concordant Care and Survival in Pancreatic Cancer. Do They Matter?

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) requires complex multidisciplinary care. European evidence suggests potential benefit from regionalization, however, data characterizing the ideal setting in the United States are sparse. Our study compares the significance of four hospital designations on guideline-concordant care (GCC) and overall survival (OS). PATIENTS AND METHODS: The Texas Cancer Registry was queried for 17,071 patients with PDAC treated between 2004 and 2015. Clinical data were correlated with hospital designations: NCI designated (NCI), high volume (HV), safety net (SNH), and American College of Surgeons Commission on Cancer accredited (ACS). Univariable (UVA) and multivariable (MVA) logistic regression were used to assess associations with GCC [on the basis of National Comprehensive Cancer Network (NCCN) recommendations]. Cox regression analysis assessed survival. RESULTS: Only 43% of patients received GCC. NCI had the largest associated risk reduction (HR 0.61, CI 0.58-0.65), followed by HV (HR 0.87, CI 0.83-0.90) and ACS (HR 0.91, CI 0.87-0.95). GCC was associated with a survival benefit in the full (HR 0.75, CI 0.69-0.81) and resected cohort (HR 0.74, CI 0.68-0.80). NCI (OR 1.52, CI 1.37-1.70), HV (OR 1.14, CI 1.05-1.23), and SNH (OR 0.78, CI 0.68-0.91) all correlated with receipt of GCC. For resected patients, ACS (OR 0.63, CI 0.50-0.79) and SNH (OR 0.50, CI 0.33-0.75) correlate with GCC. CONCLUSIONS: A total of 43% of patients received GCC. Treatment at NCI and HV correlated with improved GCC and survival. Including GCC as a metric in accreditation standards could impact survival for patients with PDAC.

Addition of Postoperative Radiation Therapy After Preoperative Chemotherapy and Surgery in Patients With Locally Advanced Endometrial Cancer Is Associated With Improved Outcomes.

Purpose: Our purpose was to examine outcomes of patients with locally advanced endometrial cancer who undergo neoadjuvant chemotherapy followed by surgery (PreCT) with/without postoperative adjuvant radiation therapy. A secondary analysis of down staging and margin clearance was made with reference to those receiving upfront surgery and then adjuvant chemotherapy (PostCT). Methods and Materials: The National Cancer Database was queried for FIGO (The International Federation of Gynecology and Obstetrics) stage III/IV locally advanced endometrial cancer cases who underwent definitive surgery from 2010 to 2016 and received chemotherapy as part of their treatment. Cases were classified into 2 cohorts: preoperative chemotherapy +/- postoperative chemotherapy cohort (PreCT) and postoperative chemotherapy cohort (PostCT) for reference for margin assessment. Cases who received preoperative radiation therapy were excluded while those who received postoperative radiation were included in the analysis. Primary endpoints were overall survival (OS), surgical margin status, rate of downstaging, and effect of adjuvant radiation therapy on OS among the PreCT cohort. Univariable (UVA) and multivariable (MVA) Cox regression analyses were performed. Results: A total of 13,369 cases were identified with 1059 in PreCT and 12,310 in PostCT cohorts. PreCT had lower OS than PostCT (UVA: hazard ratio [HR], 2.18; P < .001; MVA: HR, 1.873; P < .001). PreCT cases with negative margins, who presumably had unresectable tumors initially, also had worse OS compared with PostCT with negative margins (UVA: HR, 2.20; P < .001; MVA: HR, 1.84; P < .001); however, PreCT with negative margins had similar survival to PostCT with positive margins (UVA: HR, 0.825; P < .001; MVA: P = .885). The addition of radiation after surgery in the PreCT cohort was associated with improved survival (5-year OS 20.5% compared with 50%, respectively; UVA: HR, 0.450; P < .001; MVA: HR, 0.337; P < .001). Although fewer cases in PreCT had negative margins compared with PostCT (72% compared with 84%, P < .001), approximately 19% of cases in PreCT had lower pathologic T-stage compared with clinical T-stage and 11% had lower N-stage. Conclusions: Neoadjuvant chemotherapy was given in cases with worse oncologic prognostic factors, many of whom were likely unresectable at outset, compared with those who received postoperative chemotherapy. Although neoadjuvant chemotherapy is associated with tumor downstaging, survival is lower than with primary surgery probably because of these baseline differences. The addition of adjuvant radiation after surgery in cases who received preoperative chemotherapy is associated with improved survival.

Improving Renal Tumor Biopsy Prognostication With BAP1 Analyses.

CONTEXT.­: Active surveillance of small renal masses highlights the need for accurate prognostication of biopsies. OBJECTIVE.­: To comprehensively evaluate the accuracy of biopsies in assessing known prognostic parameters including histologic subtype by comparison with subsequent nephrectomy samples. DESIGN.­: We retrospectively identified patients at University of Texas Southwestern Medical Center, Dallas, Texas, who had a biopsy for a renal mass between 2004-2018. Biopsy samples were evaluated for known prognostic factors such as tumor grade, necrosis, sarcomatoid/rhabdoid change, and BRCA1-associated protein-1 (BAP1) status, which we previously showed is an independent prognostic factor for clear cell renal cell carcinoma. Accuracy was determined by comparison with subsequent analyses of nephrectomy specimens. Statistical analyses were performed to assess biopsy accuracy and correlation with tumor size and pathologic stage. RESULTS.­: From 805 biopsies with a diagnosis of renal neoplasm, 178 had subsequent resection of the biopsied tumor. Concordance rate for histologic subtype was 96.9% (κ [w], 0.90; 95% CI, 0.82-0.99) and excellent for small renal masses (98.8%; κ [w], 0.97; 95% CI, 0.90-1). Amongst the prognostic variables evaluated, BAP1 immunohistochemistry in clear cell renal cell carcinoma had the highest agreement (94.8%; κ [w], 0.83; 95% CI, 0.66-0.99). The presence of 1 or more aggressive features (grade 3-4, tumor necrosis, BAP1 loss, sarcomatoid/rhabdoid change) in a biopsy significantly correlated with pT stage (P = .004). CONCLUSIONS.­: Biopsy analyses showed high accuracy for subtyping renal tumors, but it underestimated several poor prognostic features. Addition of BAP1 for clear cell renal cell carcinoma may increase prognostic accuracy. If validated, routine incorporation of BAP1 immunohistochemistry in clear cell renal cell carcinoma biopsies may refine prognosis and aid in the selection of patients for active surveillance.

The impact of bridging therapy prior to CD19-directed chimeric antigen receptor T-cell therapy in patients with large B-cell lymphoma.

In the relapsed/refractory setting for treatment of large B-cell lymphoma (LBCL), chimeric antigen receptor T-cell (CAR-T) therapy has emerged as an effective treatment modality. Patients often have aggressive disease that requires prompt treatment in the form of bridging therapy (BT) for disease stabilisation while CAR-T cells are manufactured. Patients (n = 75) undergoing CAR-T therapy infusion for LBCL at our institution were identified. A total of 52 (69·3%) received BT and 23 (30·7%) received no BT (NBT). BT modalities included systemic BT (SBT) in 28 patients, radiation BT (RBT) in 14, and high-dose steroid BT (HDS) in 10. There was no difference in incidence of cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome between BT and NBT (P = 0·18 and P = 0·53 respectively). Prolonged cytopenias at Day 180 were more common in BT than NBT (50% vs. 13·3%, P = 0·04). The SBT and RBT subgroups had more cytopenias at Day 180 compared to the HDS and NBT subgroups (58·3% and 57·1% vs. 20% and 13·3% respectively, P = 0·04). Disease response at last follow-up, progression-free survival and overall survival were similar between BT, NBT, and BT subgroups. In summary, BT can be safely considered in patients undergoing CAR-T therapy. However, those undergoing BT with SBT or RBT are at higher risk of prolonged cytopenias after CAR-T therapy.

Treatment and Survival Disparities of Colon Cancer in the Texas-Mexico Border Population: Cancer Disparities in Border Population.

BACKGROUND: Previous studies have reported healthcare disparities in the Texas-Mexico border population. Our aim was to evaluate treatment utilization and oncologic outcomes of colon cancer patients in this vulnerable population. METHODS: Patients with localized and regional colon cancer (CC) were identified in the Texas Cancer Registry (1995-2016). Clinicopathological data, hospital factors, receipt of optimal treatment, and overall survival (OS) were compared between Texas-Mexico Border (TMB) and the Non-Texas-Mexico Border (NTMB) cohorts. Multivariable analysis was performed to identify risk factors associated with decreased survival. RESULTS: We identified 43,557 patients with localized/regional CC (9% TMB and 91% NTMB). TMB patients were more likely to be Hispanic (73% versus 13%), less likely to have private insurance (13% versus 21%), were more often treated at safety net hospitals (82% versus 22%) and less likely at ACS-CoC accredited hospitals (32% versus 57%). TMB patients were more likely to receive suboptimal treatment (21% versus 16%) and had a lower median OS for localized (8.58 versus 9.58 y) and regional colon cancer (5.75 versus 6.18 y, all P < 0.001). In multivariable analysis, TMB status was not associated with worse OS. Factors associated with worse survival included receipt of suboptimal treatment, Medicare/insured status, and treatment in safety net and non-accredited ACS-CoC hospitals (all P < 0.001) CONCLUSIONS: While TMB CC patients had worse OS, TMB status itself was not found to be a risk factor for decreased survival. This survival disparity is likely associated with higher rate of suboptimal treatment, Medicare/Uninsured status, and decreased access to ACS-CoC accredited hospitals.

Accessing Targeted Therapies: A Potential Roadblock to Implementing Precision Oncology?

PURPOSE: Advances in genomic techniques have led to increased use of next-generation sequencing (NGS). We evaluated the extent to which these tests guide treatment decisions. METHODS: We developed and distributed a survey assessing NGS use and outcomes to a survey pool of ASCO members. Comparisons between groups were performed with Wilcoxon two-sample, chi-square, and Fisher's exact tests. RESULTS: Among 178 respondents, 62% were male, 54% White, and 67% affiliated with academic centers. More than half (56%) indicated that NGS provided actionable information to a moderate or great extent. Use was highest (median ≥ 70% of cases) for lung and gastric cancer, and lowest (median < 25% of cases) in head and neck and genitourinary cancers. Approximately one third of respondents reported that, despite identification of an actionable molecular variant, patients were sometimes or often unable to access the relevant US Food and Drug Administration-approved therapy. When NGS did not provide actionable results, individuals reporting great or moderate guidance overall from NGS in treatment recommendations were more likely to request the compassionate use of an unapproved drug (P < .001), enroll on a clinical trial (P < .01), or treat off-label with a drug approved for another indication (P = .02). CONCLUSION: When NGS identifies an actionable result, a substantial proportion of clinicians reported encountering challenges obtaining approved therapies on the basis of these results. Perceived overall impact of NGS appears associated with clinical behavior unrelated to actionable NGS test results, including pursuing off-label or compassionate use of unapproved therapies or referring to a clinical trial.

The association of leukocyte immunoglobulin-like receptor subfamily B-4 expression in acute myeloid leukemia and central nervous system involvement.

Central nervous system (CNS) involvement in patients with acute myeloid leukemia (AML) varies, ranging from 0.6%-46%. Leukocyte immunoglobulin-like receptor B4 (LILRB4) has been shown to be critical in orchestration of infiltration of AML cells into the CNS in animal models, however it is unknown if an association exists between LILRB4 and CNS involvement (CNS+) in human patients with AML. LILRB4 was measured by flow cytometry in a heterogeneous population of fifty-six AML patients. Patients were then followed clinically for the development of CNS + . LILRB4 was positive in 91 % of patients with CNS + compared to 38 % without CNS involvement (p < 0.002). In logistic analysis: age, BMI, serum albumin and positive LILRB4 were predictive for CNS+ [OR, 95 % CI, p-value]: 0.95, 0.92-0.99, p < 0.01; 0.85, 0.73-0.998, p < 0.05; 0.23, 0.066-0.78, p < 0.02; 16.46, 1.93-140.2, p < 0.02, respectively. This finding of the association of LILRB4 with CNS + in combination with earlier findings suggests that LILRB4 has a mechanistic role in infiltration of the CNS and may provide insight into the pathogenesis of AML seeding the CNS. Moreover, this proof of concept and the findings in the present study may lead to the development of innovative and novel therapies to improve the lives of patients with AML.

Comparative cost analysis between definitive radiotherapy and transoral surgery for oropharyngeal squamous cell carcinoma: A SEER-Medicare analysis.

INTRODUCTION: Primary radiotherapy (RT) and transoral surgery (TOS) are effective local therapy treatments for oropharyngeal squamous cell carcinoma (OPSCC), but their cost profiles differ. We compared the one-year costs of these competing treatments using a large claims-based database. METHODS: Eligible individuals were patients in the SEER-Medicare registry diagnosed with OPSCC between 2000 and 2011. Patients were categorized as receiving either primary RT +/- chemotherapy, or TOS +/- adjuvant RT or chemoradiotherapy (CRT), and all treatment costs from 1 month prior to diagnosis to 1 year after diagnosis were calculated. Univariable and multivariable linear regression models were used to determine predictors of payer expenditure. Patient-borne pharmacy costs were also analyzed. RESULTS: The cohort included 3497 patients (73% RT, 27% TOS), of whom 73% were locally advanced. The mean total 13 month costs for RT alone, CRT, TOS alone, TOS + RT and TOS + CRT were $39,083, $63,537, $25,468, $36,592, and $99,919, respectively, for early-stage patients. For locally advanced individuals, the mean costs were $45,049, $68,099, $40,626, $53,729, and $71,397, respectively. On multivariable analysis, the adjusted increase in total costs versus RT alone were $21,844, -$5431, $7984, and $28,581 for CRT, TOS alone, TOS + RT, and TOS + CRT, respectively. The difference between CRT and TOS + RT became non-significant for TOS patients undergoing transoral surgery plus neck dissection. Cisplatin was associated with significant less cost than cetuximab and taxane-based chemotherapy. CONCLUSION: In this population of elderly patients, transoral surgery was generally associated with less expensive treatment, with the addition of chemotherapy serving as the main driver of increased cost.

Intraoperative Assessment of DIEP Flap Breast Reconstruction Using Indocyanine Green Angiography: Reduction of Fat Necrosis, Resection Volumes, and Postoperative Surveillance.

BACKGROUND: This study aims to characterize the effect of laser-assisted indocyanine green fluorescence angiography on fat necrosis and flap failure in deep inferior epigastric artery perforator (DIEP) flap breast reconstruction. METHODS: A retrospective review was performed on 1000 free flaps for breast reconstruction at a single center from 2010 to 2017. Indocyanine green angiography was used after completion of recipient-site anastomoses to subjectively assess for areas of hypoperfusion. A multivariable logistical analysis was conducted with 24 demographic and surgical factors and their effects on fat necrosis and flap failure. RESULTS: Five hundred six DIEP flaps were included in the statistical analyses. Thirteen percent of flaps had fat necrosis. Indocyanine green angiography was used for 200 flaps and was independently associated with a decrease in the odds of fat necrosis (OR, 0.38; p = 0.004). There was no reduction in flap failure rates when using indocyanine green angiography (OR, 1.15; p = 0.85). However, there was a decrease in flap loss with increasing venous coupler diameter (OR, 0.031 per 1-mm increase; p = 0.012). The 84.9-g higher weight of resected tissue before inset without indocyanine green angiography versus the weight of the tissue resected with indocyanine green angiography was statistically significant (p = 0.01). Per single incident of fat necrosis, our cohort underwent an additional 0.69 revision procedures, 1.22 imaging studies, 0.77 biopsies, and 1.7 additional oncologic office visits. CONCLUSION: Intraoperative indocyanine green fluorescence angiography decreases the odds of fat necrosis, saves volume when flap trimming at inset, and can significantly reduce the postoperative surveillance burden in DIEP-based breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Timing, Sites, and Correlates of Lung Cancer Recurrence.

INTRODUCTION: Understanding temporal and anatomic patterns of lung cancer recurrence could guide disease management and monitoring. However, these data are not available in population-based datasets and are not routinely recorded in clinical trials. MATERIALS AND METHODS: We identified cases of stage 1 to 3 lung cancer diagnosed January 1, 2000, to December 31, 2017, in the tumor registry of a National Cancer Institute-designated comprehensive cancer center. For cases with documented disease recurrence, we recorded anatomic site(s) and timing. We estimated time to recurrence using Kaplan-Meier methods. Associations between case characteristics and recurrence features were assessed using univariable and multivariable logistic regression models and Cox regression models. RESULTS: A total of 1619 cases of stage 1 to 3 lung cancer from 1549 patients were included in the analysis. Of these, 466 (30%) patients developed recurrent lung cancer. The most common type of first recurrence was distant disease, most commonly central nervous system (CNS) (37%). In multivariable analyses, race (P = .02) and primary treatment modality (P < .001) correlated with recurrent disease, whereas tumor histology (P = .004) and primary treatment modality (P < .001) were associated specifically with distant recurrence. Patient age (P = .05) and initial TNM stage (P = .001) correlated with timing of recurrence. CONCLUSION: In this single-center series of stage 1 to 3 lung cancer, recurrent disease was associated with race, histology, and treatment modality, and most commonly occurred in the CNS. Modulation of clinical and radiographic disease monitoring according to recurrence risk, timing, and site may offer a means to identify future lung cancer when it remains asymptomatic and highly treatable.

Preoperative predictive model and nomogram for disease recurrence following radical nephroureterectomy for high grade upper tract urothelial carcinoma.

PURPOSE: To identify preoperative risk factors for disease recurrence, following radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), and to create a predictive nomogram. MATERIALS AND METHODS: Based on a multicenter database, we identified patients who underwent RNU due to high grade UTUC. Urothelial carcinoma of the bladder or contralateral UTUC was not considered as recurrence. Cox regression model was used to determine the effect of different preoperative variables as predictors of recurrence. RESULTS: Two hundred and forty-five patients were included in the analysis. The 2 and 5 years recurrence rates were 16.3% and 19.2%, respectively. Factors associated with recurrence on univariable analysis were sessile architecture hazard ratio (HR) 3.16 (95% CI, 1.38-7.26, P = 0.006), ≥cT3 disease HR 2.30 (95% CI, 1.12-4.72, P= 0.023), age >65 HR 2.02 (95% CI, 1.00-4.05, P= 0.048), Eastern Cooperative Group > 0 HR 1.98 (95% CI, 1.09-3.57, P= 0.023), hydronephrosis HR 1.93 (95% CI, 1.04-3.57, P= 0.035). Higher hemoglobin levels HR 0.81 (95% CI, 0.69-0.96, P= 0.013) and preoperative estimated glomerular filtration rate ≥ 50 HR 0.48 (95% CI, 0.25-0.92, P = 0.028) were associated with lower probability for recurrence. Multivariable analysis identified sessile architecture as the only independent predictor of recurrence HR 2.52 (95% CI, 1.09-5.86, P= 0.0308). C-index of 0.71 was calculated for a predictive model including all variables in the multivariable analysis, indicating good predictive accuracy. A nomogram predicting 2 and 5 year recurrence free probability was developed accordingly. CONCLUSIONS: Based on a multicenter database, we developed a nomogram with good predictive accuracy for recurrence following RNU. This may serve as an aid in decision-making regarding the use of neoadjuvant chemotherapy.

Open, Laparoscopic, and Robotic Inguinal Hernia Repair: Outcomes and Predictors of Complications.

BACKGROUND: The robotic approach to an inguinal hernia has not been compared head to head with the open and laparoscopic techniques in randomized controlled trials. Furthermore, long-term outcomes for robotic inguinal hernia repair (RHR) are lacking. In this study, we compared laparoscopic inguinal hernia repair (LHR) and RHR with open inguinal hernia repair (OHR) in veteran patients performed by surgeons most familiar with each approach. METHODS: A retrospective single-institution analysis of 1299 inguinal hernia repairs performed at the VA North Texas Health Care System between 2005 and 2017 was undertaken. Three surgeons performed the operations, each an expert in one approach, and there was no crossover in techniques. A total of 1100 OHRs, 128 LHRs, and 71 RHRs were performed. Univariable analysis was undertaken to determine associations between techniques and outcomes (OHR versus LHR; OHR versus RHR; LHR versus RHR). Setting complications as a dependent variable, multivariable analyses were undertaken to determine an association with complications as well as independent predictors of complications. RESULTS: Patient demographics were similar among groups except for age that was higher in the OHR cohort. The average follow-up was 5.2 ± 3.4 y. In the present report, recurrence was associated with a higher rate in the RHR versus OHR (5.6% versus 1.7%; P < 0.02), but not in the LHR versus OHR (3.9% versus 1.9%; P = 0.09). Inguinodynia was more likely to occur in both the LHR and RHR compared with the OHR (9.4% and 14.1 versus 1.5%; both P's < 0.001). Urinary retention was also more common in the LHR and RHR than in the OHR (5.5% and 5.6% versus 1.8%, both P's < 0.05) as was the rate of overall complications (34.4% and 38.0% versus 11.2%, both P's < 0.001). Multivariable regression analysis showed femoral hernias, ASA, serum albumin, operative room time, a recurrent hernia, and the minimally invasive approaches were independent predictors of overall complications. CONCLUSIONS: Outcomes in the OHR cohort were, in general, superior compared with both the LHR and RHR. However, these strategies should be viewed as complementary. The best approach to an inguinal hernia repair rests on the specific expertise of the surgeon.

Comparative effectiveness of primary radiotherapy versus surgery in elderly patients with locally advanced oropharyngeal squamous cell carcinoma.

OBJECTIVES: To determine the comparative effectiveness of primary radiotherapy (RT) and primary surgery (PS) for locally advanced oropharyngeal squamous cell carcinoma (OPSCC). MATERIALS AND METHODS: Eligible individuals were patients in the SEER-Medicare registry diagnosed with locally advanced OPSCC between 2000 and 2011. Patients were categorized as receiving either primary RT ±â€¯chemotherapy, or PS ±â€¯adjuvant RT or chemoradiotherapy (CRT). Overall survival (OS) was analyzed using Cox multivariable analysis (MVA). Risks of gastrostomy dependence (GD), esophageal stricture (ES), and osteoradionecrosis (ORN) were analyzed using logistic regression. RESULTS: A total of 2754 patients (69% RT, 31% PS) were included in this cohort, with a median age of 72 years. Patients treated with RT, CRT and PS experienced 3-year OS outcomes of 36.1%, 52.8%, and 54.9%, respectively (p < 0.001). Increasing age, unmarried status, increasing comorbidity, lower income, base of tongue (BOT) site, higher stage, no prior PET, and RT alone (but not CRT) were associated with inferior OS. Independent predictors of GD at 6 months included black race, BOT site, advanced stage, and CRT. The risks of ORN and stricture were not associated with treatment modality. Concurrent chemotherapy improved OS with definitive RT but had no impact in adjuvant RT. Only cisplatin- and taxane-containing regimens improved OS, but all concurrent agents, including cetuximab, significantly worsened GD. CONCLUSION: Local therapy decisions for locally advanced OPSCC must be individualized, with CRT increasing acute and chronic GD. The differential survival impact of concurrent chemotherapy in the definitive and adjuvant setting may be a consideration in decision-making.

HORMAD1 Is a Negative Prognostic Indicator in Lung Adenocarcinoma and Specifies Resistance to Oxidative and Genotoxic Stress.

Cancer testis antigens (CTA) are expressed in testis and placenta and anomalously activated in a variety of tumors. The mechanistic contribution of CTAs to neoplastic phenotypes remains largely unknown. Using a chemigenomics approach, we find that the CTA HORMAD1 correlates with resistance to the mitochondrial complex I inhibitor piericidin A in non-small cell lung cancer (NSCLC). Resistance was due to a reductive intracellular environment that attenuated the accumulation of free radicals. In human lung adenocarcinoma (LUAD) tumors, patients expressing high HORMAD1 exhibited elevated mutational burden and reduced survival. HORMAD1 tumors were enriched for genes essential for homologous recombination (HR), and HORMAD1 promoted RAD51-filament formation, but not DNA resection, during HR. Accordingly, HORMAD1 loss enhanced sensitivity to γ-irradiation and PARP inhibition, and HORMAD1 depletion significantly reduced tumor growth in vivo These results suggest that HORMAD1 expression specifies a novel subtype of LUAD, which has adapted to mitigate DNA damage. In this setting, HORMAD1 could represent a direct target for intervention to enhance sensitivity to DNA-damaging agents or as an immunotherapeutic target in patients.Significance: This study uses a chemigenomics approach to demonstrate that anomalous expression of the CTA HORMAD1 specifies resistance to oxidative stress and promotes HR to support tumor cell survival in NSCLC. Cancer Res; 78(21); 6196-208. ©2018 AACR.

Institutional Scientific Review of Cancer Clinical Research Protocols: A Unique Requirement That Affects Activation Timelines.

PURPOSE: The National Cancer Institute (NCI) requirement that clinical trials at NCI-designated cancer centers undergo institutional scientific review in addition to institutional review board evaluation is unique among medical specialties. We sought to evaluate the effect of this process on protocol activation timelines. METHODS: We analyzed oncology clinical trials that underwent full board review by the Harold C. Simmons Comprehensive Cancer Center Protocol Review and Monitoring Committee (PRMC) from January 1, 2009, through June 30, 2013. We analyzed associations between trial characteristics, PRMC decisions, protocol modifications, and process timelines using the χ2 test, Fisher's exact test, Wilcoxon rank sum test, Kruskal-Wallis test, and logistic regression. RESULTS: A total of 226 trials were analyzed. Of these, 77% were industry sponsored and 23% were investigator initiated. The median time from submission to PRMC approval was 55 days. The length of review was associated with trial phase, timing of approval, and number of committee changes/clarifications requested. The median process time was 35 days for those approved at first decision, 68 days for second decision, and 116 days for third decision ( P < .001). The median process time was 39 days if no changes/clarifications were requested, 64 days for one to three changes/clarifications, and 73 days for four or more changes/clarifications ( P < .001). Requested changes/clarifications had a greater effect on industry-sponsored trials than on investigator-initiated trials. CONCLUSION: NCI-mandated institutional scientific review of oncology clinical trials contributes substantially to protocol activation timelines. Further evaluation of this process and the value added to research quality is warranted.

Thoracic Oncology Clinical Trial Eligibility Criteria and Requirements Continue to Increase in Number and Complexity.

INTRODUCTION: Eligibility criteria and screening procedures are designed to optimize the scientific yield and maximize the safety of clinical trials. However, they may also heighten trial complexity, hinder enrollment, decrease generalizability, and increase costs. We analyzed the types and number of eligibility criteria and screening procedures among thoracic oncology clinical trials sponsored or endorsed by the Eastern Cooperative Oncology Group. METHODS: We identified trials and obtained protocols from the Eastern Cooperative Oncology Group website. Eligibility criteria were grouped and categorized as comorbidity (classified by organ system), administrative requirements, prior treatment, and measurable disease requirements. Associations between trial characteristics and eligibility criteria were analyzed by using the Kruskal-Wallis and Wilcoxon tests. RESULTS: A total of 74 lung cancer trials activated in 1986-2016 were identified. The total number of eligibility criteria was associated with trial principal therapy (a median of nine for surgical, 18 for radiation, and 20 for medical therapy [p = 0.02]), trial primary end point (a median of 20 for overall survival, 28 for progression-free survival, and 17 for other [p = 0.001]), number of therapies (p = 0.05), and year of activation (a median of 16 for 1986-1995, 19 for 1996-2005, and 27 for 2006-2016 [P < 0.001]). The increase in trial eligibility requirements over time was limited to medical therapy trials. Over time, there was also an increase in blood test screening procedures (p = 0.05) but not in imaging, cardiac assessment, or pulmonary function screening procedures. CONCLUSIONS: The number of eligibility criteria and screening procedures in medical therapy lung cancer clinical trials continues to rise. Continued efforts to simplify protocol eligibility and procedures are warranted to promote trial adherence, enrollment, completion, and generalizability.

Time and Effort Required for Tissue Acquisition and Submission in Lung Cancer Clinical Trials.

BACKGROUND: Increasingly, analysis of tumor tissue samples for predictive and pharmacodynamic biomarkers is incorporated into lung cancer clinical trials. We determined the time and effort required for tissue acquisition and submission. PATIENTS AND METHODS: We analyzed data from patients enrolled from 2009 to 2016 at UT Southwestern onto lung cancer trials with mandatory or optional submission of tumor tissue. We collected dates of treatment-related events and staff communications; nature of tissue requirement and biomarker analysis; and location of archival tissue. Associations between case characteristics, clinical intervals, and number of staff communications were analyzed by Fisher's exact test, Wilcoxon 2-sample test, and Kruskal-Wallis test. RESULTS: We identified 129 patients enrolled onto 19 clinical trials, of whom 108 (84%) ultimately received study therapy. For cases in which tissue submission was required if available or optional, 16% and 0%, respectively, had tissue sent. The median interval between consent and treatment was 28 (interquartile range, 11-43) days if tissue was requested and 7 (interquartile range, 6-13) days if tissue was not requested (P < .001). Among cases with requested tissue, the median number of related research staff communications was 3 (range, 0-10). Over time, the number of staff communications increased (P < .001). Location of archival tissue was not associated with number of staff communications or treatment intervals. CONCLUSION: Lung cancer clinical trial requirements for tissue acquisition and submission affect the time to treatment initiation and require increasing staff effort. Improved systems to expedite these processes, as well as use of blood- or imaging-based biomarkers, may help address these issues.

Aspirin/antiplatelet agent use improves disease-free survival and reduces the risk of distant metastases in Stage II and III triple-negative breast cancer patients.

PURPOSE: The objective is to define the therapeutic role of antiplatelet agents in a triple-negative breast cancer (TNBC) population. METHODS: We performed retrospective analysis using the UTSW TNBC registry containing data from 222 Stage II-III TNBC patients treated between 1998 and 2016. Univariate analysis and multivariable logistic regression models were constructed to identify factors associated with disease-free survival (DFS), distant metastases rate (DMR), and overall survival outcomes. Antiplatelet drug use was determined by review of electronic medical records. RESULTS: A total of 65 patients used antiplatelet (AP) agents, and 157 patients did not use AP agents. Median follow-up for AP and non-AP groups was 41.3 and 40.9 months, respectively. There was an improvement in the AP group compared with the control group in 5-year DFS (80.4% at 5 years compared with 62.3% in the control group, p = 0.04) and 5-year DMR (8.8 vs. 31.9%, p = 0.007). In multivariate analysis, AP use was found to be significantly associated with improvements in DFS and DMR. CONCLUSIONS: We illustrate that antiplatelet agent use improves DMR and DFS among a stage II and III TNBC population despite our short follow-up evaluation. Longer follow-up evaluation will be required to determine additional outcome advantage for antiplatelet agent use. Our findings support consideration of investigation of antiplatelet therapy as an adjunctive therapy for TNBC at high risk for disease recurrence.