National Comprehensive Cancer Center Research Articles

Evaluation of control arm quality in recent radiation oncology randomized clinical trials.

295 Background: Randomized controlled trials (RCTs) are designed to provide the highest levels of evidence for clinical practice; consequently, RCTs are the mainstay for creating guidelines and approving new treatments. It is ethically essential for patients assigned to the control arm in RCTs to receive standard-of-care treatment. This serves to protect patients, optimize adequate treatment, and ensures that RCT findings are compared to current standard-of-care therapy – an ethical imperative of RCT design and implementation. Oncologic medical trials investigating new systemic agents for cancer have a high proportion of RCTs with inadequate control arms (PMID 31046071). It is unknown whether this finding is prevalent in oncologic trials investigating radiation therapy (RT) for cancer. Methods: We identified registered clinical trials investigating RT in patients with cancer over the past decade. ClinicalTrials.gov was queried for RT as the intervention and cancer and other related terms as the condition between 1/1/13 and 1/1/23. Exclusion criteria included trials with incomplete status or non-oncologic indications. Trials were categorized by indication/primary disease site, first posted date, investigational arm, control arm, and sponsor/collaborator. Each control arm was analyzed, and the standard of care was determined according to National Comprehensive Cancer Center Network (NCCN) guidelines at the time of first posting on ClinicalTrials.gov. Results: A total of 508 interventional studies with results registered on ClinicalTrials.gov were included. Of these, 360 single-arm studies were excluded. 116 studies investigating a treatment other than RT were excluded. 20 studies that were not completed were excluded. The remaining 12 studies were included in the final analysis. Of the included trials, 2 each investigated RT usage in central nervous system, prostate, head and neck, and breast disease sites, and 1 each for lung, hepatobiliary, rectal, and bone disease sites. A majority of the trials were industry-funded (83%), and over 2/3 of studies took place in the United States (75%). 100% of the trials were found to have an adequate control arm per the corresponding NCCN guidelines. Conclusions: 100% of oncologic RCTs investigating radiation therapy for cancer were found to have an adequate control arm. This finding contrasts with medical oncology trials, which have been shown to have a high proportion of RCTs with inadequate control arms. This disparity highlights the importance of designing oncologic RCTs with adequate control arms, which is crucial for providing the highest level of evidence to guide optimal clinical practice and ensure the safety of patients. These findings indicate that the field of Radiation Oncology is ensuring ethical trial design with adequate control arm treatments and emphasizes the need for a continued focus on improving the quality of ethical oncologic research trials.

Clinical Implementation of DIGEST as an Evidence-Based Practice Tool for Videofluoroscopy in Oncology: A Six-Year Single Institution Implementation Evaluation.

Clinical implementation of evidence-based practice (EBP) tools is a healthcare priority. The Dynamic Grade of Swallowing Toxicity (DIGEST) is an EBP tool developed in 2016 for videofluoroscopy in head and neck (H&N) oncology with clinical implementation as a goal. We sought to examine: (1) feasibility of clinical implementation of DIGEST in a national comprehensive cancer center, and (2) fidelity of DIGEST adoption in real-world practice. A retrospective implementation evaluation was conducted in accordance with the STARI framework. Electronic health record (EHR) databases were queried for all consecutive modified barium swallow (MBS) studies conducted at MD Anderson Cancer Center from 2016 to 2021. Implementation outcomes included: feasibility as measured by DIGEST reporting in EHR (as a marker of clinical use) and fidelity as measured by accuracy of DIGEST reporting relative to the decision-tree logic (penetration-aspiration scale [PAS], residue, and Safety [S] and Efficiency [E] grades). Contextual factors examined included year, setting, cancer type, MBS indication, and provider. 13,055 MBS were conducted by 29 providers in 7,842 unique patients across the lifespan in diverse oncology populations (69% M; age 1-96 years; 58% H&N cancer; 10% inpatient, 90% outpatient). DIGEST was reported in 12,137/13,088 exams over the 6-year implementation period representing 93% (95% CI: 93-94%) adoption in all exams and 99% (95% CI: 98-99%) of exams excluding the total laryngectomy population (n = 730). DIGEST reporting varied modestly by year, cancer type, and setting/provider (> 91% in all subgroups, p < 0.001). Accuracy of DIGEST reporting was high for overall DIGEST (incorrect SE profile 1.6%, 200/12,137), DIGEST-safety (incorrect PAS 0.4% 51/12,137) and DIGEST-efficiency (incorrect residue 1.2%, 148/12,137). Clinical implementation of DIGEST was feasible with high fidelity in a busy oncology practice across a large number of providers. Adoption of the tool across the lifespan in diverse cancer diagnoses may motivate validation beyond H&N oncology.

Clinical Outcomes for BRCA Pathogenic Variant Carriers With Breast Cancer Undergoing Breast Conservation

Although most women with BRCA-associated breast cancer choose bilateral mastectomy, current guidelines support breast-conserving therapy as an option. As the indications for genetic testing expand and targeted therapies emerge, understanding the outcomes of breast-conserving therapy in the population of patients choosing breast conservation is important. To describe the clinical outcomes of women with BRCA-associated breast cancer who were treated with breast-conserving therapy, including the risks of ipsilateral and contralateral cancer events and bilateral mastectomy-free survival. This cohort study conducted at a single-institution academic national comprehensive cancer center included 172 women identified from a prospectively maintained database who had pathogenic BRCA1/2 variants and were treated with breast-conserving therapy from January 1, 1977, to December 31, 2021. Clinical and pathologic characteristics for patients with BRCA1 and BRCA2 were compared, and estimates of overall survival, bilateral mastectomy-free survival, distant disease-free survival, risk of ipsilateral breast cancer, and risk of contralateral cancer were computed. The cohort included 172 women (mean [SD] age, 47.1 [11.7] years), with 42 (24.4%) receiving a diagnosis of breast cancer prior to 40 years of age. Compared with BRCA2 variant carriers (80 [46.5%]), women with BRCA1 variants (92 [53.5%]) were younger at breast cancer diagnosis and tended to have more advanced tumors, which were more likely to be hormone receptor negative and higher grade. At a median follow-up of 11.8 years (IQR, 5.7-18.2 years), estimates of 10-year survival and risk were: overall survival, 88.5% (95% CI, 83.1%-94.2%); bilateral mastectomy-free survival, 70.7% (95% CI, 63.3%-78.9%); risk of an ipsilateral breast cancer event, 12.2% (95% CI, 5.8%-18.2%); and risk of contralateral cancer, 21.3% (95% CI, 13.3%-28.6%). Risks continued to increase after 10 years of follow-up. In this cohort study, although women with breast cancer and pathogenic BRCA1/2 variants treated with breast-conserving therapy had above-average risks of ipsilateral and contralateral breast cancer events, most did not have another cancer event and remained bilateral mastectomy free. These findings may be useful for informing patients with BRCA variants choosing breast conservation.

Real-world Experience of Posaconazole Therapeutic Drug Monitoring in Oncology Patients: Clinical Implications of Hypoalbuminemia as a Predictor of Subtherapeutic Posaconazole Levels.

Posaconazole maintains broad antifungal activity and is employed for prevention and treatment of invasive fungal infections in oncology patients. Older formulations required therapeutic drug monitoring, and specific plasma drug levels have been recommended. This study evaluated factors associated with subtherapeutic concentrations with the newer delayed-release tablet formulation. In this retrospective, single-center cohort study at a national comprehensive cancer center, all oncology patients receiving delayed-release posaconazole at standard dosing of 300 mg orally per day from 06/2021 to 07/2023 with plasma drug concentration evaluation were identified. Demographic, clinical, and laboratory data were evaluated to identify risk factors associated with subtherapeutic drug levels at targets of ≥1.25 µg/mL and ≥1.8 µg/mL. Of 110 patients identified, 98 met criteria for inclusion in the study. The median time from initiation of posaconazole to drug level assessment was 13 days, and the median concentration was 1.29 µg/mL. Of the 22 patients receiving posaconazole for prophylaxis, 5 (22.7%) failed to achieve concentrations ≥0.7 µg/mL, and of 76 patients receiving posaconazole for treatment, 38 (50%) failed to achieve concentrations of ≥1.25 µg/mL. In multivariable analysis, albumin of ≤3 g/dL and ideal body weight ≥60 kg were found to be associated with subtherapeutic levels. For a higher target of ≥1.8 µg/mL, only albumin ≤3 g/dL was associated with subtherapeutic levels for the variables evaluated. A higher initial dosing strategy and therapeutic drug monitoring for oncology patients with albumin ≤3 g/dL receiving posaconazole, particularly for the treatment of invasive fungal infection, could be considered.

Abstract 1305: Comparison of HPV-DNA testing to PET-CT imaging as prognostic test following definitive treatment for cervical cancer: A retrospective proof-of-concept study

Abstract Cervical cancer is a significant global health issue, with oncogenic HPV-High Risk (HPV) responsible for over 99% of cases. Despite the prevalence of HPV-related malignancies, current guidelines by the National Comprehensive Cancer Center (NCCN) do not recommend post-treatment HPV-DNA testing. Instead, PET-CT imaging is recommended as a prognostic test. This retrospective proof-of-concept study aims to evaluate current NCCN guidelines and examines whether post-treatment HPV-HR DNA testing is a cost-effective, reliable alternative to PET-CT imaging in cervical cancer prognosis. Methods: The study included female patients diagnosed with cervical or vaginal carcinomas (2011-2021), ensuring comprehensive records of both pre-treatment and post-treatment high-risk HPV (HPV-HR) testing, alongside PET-CT imaging results. Utilizing the FDA-approved HPV-HR DNA test, capable of detecting 14 oncogenic HPV strains, the study conducted rigorous statistical analyses via STATA software to determine significance of the study results. Results: Our analysis of 53 patients who met the inclusion criteria demonstrated that post-treatment assessments using both HPV status and PET-CT imaging exhibited high levels of sensitivity and specificity, as well as impressive negative and positive predictive values (NPV and PPV, respectively). There was a statistically significant correlation between the likelihood of cancer recurrence and the results obtained from HPV status and PET-CT imaging post-treatment (p-value &amp;lt; 0.001). A critical observation was the superior sensitivity and improved NPV of post-treatment HPV status compared to PET-CT scans. Specifically, the sensitivity for HPV status post-treatment was quantified at 92.31, surpassing the 76.92 sensitivity rating of PET-CT scans. Furthermore, the NPV for post-treatment HPV status was measured at 97.44, which is better than the 92.31 NPV for PET-CT scans. Notably, no patients with negative post-treatment HPV-HR tests had a recurrence. Discussion: The results of this study underscore the clinical significance of assessing HPV-HR DNA status post-treatment, particularly when HPV-HR DNA is negative. If future prospective studies confirm these findings, it may eliminate the need for post-treatment PET-CT scans, providing significant survivorship benefits for patients by reducing follow-up visits and eliminating unnecessary imaging. This would also result in substantial financial savings, estimated to be over $75,000,000 per year in the US alone, based on 2023 data. The limitations of the study include small sample size, single-institution data, and biases associated with retrospective studies. Future multi-institutional prospective studies are necessary to improve current guidelines further and validate the findings of this study. Citation Format: Cameron Huddleston, Aya Bou Fakhreddine, Stephanie Stroever, Robert Young, Naresh Sah, Komaraiah Palle, Mark Reedy. Comparison of HPV-DNA testing to PET-CT imaging as prognostic test following definitive treatment for cervical cancer: A retrospective proof-of-concept study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1305.

Abstract 1002: The historically black colleges and universities cancer trial consortium: A way forward to diversifying cancer clinical trials

Abstract The National Comprehensive Cancer Center Network cancer guidelines state that the best management for a cancer patient is on a clinical trial. However, the demographics of 74 registration trials for oral cancer therapies from 2009 - 2019 show only 2.5% of participating patients were Black. Similarly, of the 3,593 patients enrolled in all registration trials for new cancer drugs approved by the FDA in 2019, only 4% were Black patients. A third analysis showed that between 2008 and 2018, only 3.1% of cancer trial patients were Black. The underrepresentation of Black patients in cancer clinical trials is a complex issue that requires a multifaceted solution. Complicated, interdependent causes include, but are not limited to system, provider, and patient bias. Increasing globalization of clinical trials also contributes to a widening gap in Black patient enrollment. Achieving diversity among clinical trial participants requires intention in study design regarding accrual sites and outreach, and involvement of a diverse trial workforce. The ideal clinical trial system would minimize system, provider, and patient biases. Such a system already exists in the Historically Black Colleges and Universities (HBCU) system. HBCUs represent 3% of institutions of higher education in the USA, yet they enroll 16% of Black students and confer 24% of all baccalaureate degrees earned by Black students. 40% of Black engineers, 50% of Black lawyers, 70% of Black physicians, and a staggering 80% of Black judges attended an HBCU. HBCUs are exceptional at impacting communities of Color and have been doing so for centuries. The HBCU Cancer Trials Consortium (HBCU CTC) is a network of HBCUs and Ally institutions that aims to bring innovative cancer clinical trials to historically underserved communities and honor the legacy of HBCUs, which have consistently and successfully served underserved communities for over a century. The HBCU CTC will oversee and conduct cancer clinical trials at member institutions. We envision founding flagship members to include HBCUs that provide graduate medical education and training, such as Howard, Meharry, Charles Drew, and Morehouse. Non-HBCUs committed to the mission are invited to join the consortium as Ally institutions (eg. MSIs). Membership is not exclusive of membership in other cancer consortia. The HBCU CTC will provide shared resource services for member institutions that lack expertise or funding to conduct services locally (eg. data management, DSMB, biostatistics, a cancer focused IRB, central radiology, and central pathology). The Consortium will also work to develop local infrastructure support for the conduct of cancer clinical trials at member institutions. Citation Format: Sheldon L. Holder, Robert A. Winn, Wafik S. El-Deiry. The historically black colleges and universities cancer trial consortium: A way forward to diversifying cancer clinical trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1002.

Radiation-Induced Cerebral Contrast Enhancements Strongly Share Ischemic Stroke Risk Factors

Background and purposeRadiation-induced cerebral contrast enhancements (RICE) are frequent following both photon and particularly proton radiotherapy and are associated with a significant risk for neurologic morbidity. Nevertheless, risk factors are poorly understood. A more robust understanding of RICE risk factors is crucial to improve management and offer adaptive therapy at the outset and during follow-up. Materials and methodsWe analyzed the comorbidities in detail of 190 consecutive adult patients treated at a single European national comprehensive cancer center with proton radiotherapy (PRT; 54Gy RBE) for LGG from 2010 to 2020 who were followed with serial clinical exams and magnetic resonance imaging for in median 5.6 years. ResultsClassical vascular risk factors including age (≥50 years vs. <50 years: 1.6-fold; p=0.0024), hypertension (2.7-fold; p=0.00012) and diabetes (11.7-fold; p=0.0066) were observed more frequently in the cohort who developed RICE. Dyslipidemia (2.1-fold), overweight (2.0-fold) and smoking (2.6-fold) as well as history of previous stroke (1.7-fold) were also more frequently observed in the RICE cohort, though these factors did not reach threshold for significance. Multivariable regression modelling supported the influence of age (p=0.05), arterial hypertension (p=0.01) and potentially male sex (p=0.02), diabetes (p=0.0008) and smoking (p=0.001) on RICE occurrence over time, independent of each other and further vascular risk factors. If RICE occurred, bevacizumab treatment was two-fold more frequently needed in the cohort with vascular risk factors, but RICE long-term prognosis did not differ between the RICE subcohort with and without vascular risk factors. ConclusionsThis is the first report in the literature demonstrating RICE strongly share vascular risk factors with ischemic stroke, which further enhances the nebulous understanding of the multifactorial pathophysiology of RICE. Classical vascular risk factors, especially age, hypertension and diabetes clearly correlated independently with RICE risk. Risk-adapted screening and management for RICE can be directly derived from this data to assist in clinical management.

Tumor-treating fields dosimetry in glioblastoma: Insights into treatment planning, optimization, and dose-response relationships.

Tumor-treating fields (TTFields) are currently a Category 1A treatment recommendation by the US National Comprehensive Cancer Center for patients with newly diagnosed glioblastoma. Although the mechanism of action of TTFields has been partly elucidated, tangible and standardized metrics are lacking to assess antitumor dose and effects of the treatment. This paper outlines and evaluates the current standards and methodologies in the estimation of the TTFields distribution and dose measurement in the brain and highlights the most important principles governing TTFields dosimetry. The focus is on clinical utility to facilitate a practical understanding of these principles and how they can be used to guide treatment. The current evidence for a correlation between TTFields dose, tumor growth, and clinical outcome will be presented and discussed. Furthermore, we will provide perspectives and updated insights into the planning and optimization of TTFields therapy for glioblastoma by reviewing how the dose and thermal effects of TTFields are affected by factors such as tumor location and morphology, peritumoral edema, electrode array position, treatment duration (compliance), array "edge effect," electrical duty cycle, and skull-remodeling surgery. Finally, perspectives are provided on how to optimize the efficacy of future TTFields therapy.

Care Patterns and Barriers to Outpatient Care for Adults with Acute Myeloid Leukemia (AML) Following Intensive Chemotherapy at National Comprehensive Cancer Network (NCCN) Institutions

Background: Prolonged hospitalization following intensive (re)induction chemotherapy until resolution of cytopenias is the current standard of care for adults with acute myeloid leukemia (AML), but this approach is costly, resource intense, contributory to hospital bed shortages, and negatively impacts patients' quality of life (QOL). Early hospital discharge (EHD) immediately following completion of chemotherapy has been proposed as an alternative and has proven safe at select institutions. Here, we conducted a National Comprehensive Cancer Center (NCCN) survey, through its Best Practices Committee (BPC), to examine discharge practices for adults with AML at other major cancer centers to better understand interest in, and barriers to, adopting an EHD approach more broadly. Methods: NCCN is a non-profit alliance of 33 cancer centers in the U.S. The survey was developed by 2 physicians at one center and piloted at 2 other centers. The NCCN BPC, which is composed of senior physician, nursing, and administrative leaders from NCCN Member Institutions, distributed the survey in early 2023 via a web-based survey tool (SurveyMonkey, San Mateo, CA) to a representative at each center, requesting completion by a content area expert. No incentives were offered for completion. Data were analyzed using descriptive statistics. Results: 30/33 (91%) centers completed the survey, 60% of which treat &amp;gt;100 AML patients annually and 45% treat over half of their patients with intensive chemotherapy (7+3 or regimens with a high-dose cytarabine backbone). All centers perform allogeneic hematopoietic cell transplantations (HCT). There was no difference in the proportion of intensively treated patients across centers by patient volume. Following (re)induction therapy, 80% of institutions keep patients hospitalized until blood count recovery, whereas 20% attempt to discharge patients early if medically stable and logistics permit. Concerns regarding patient safety, housing, and caregiver availability were the main reasons for keeping patients hospitalized ( Figure 1). In contrast, following post-remission (“consolidation”) therapy, 87% of centers discharge patients early. Concerns regarding increased care needs, worse functional status, and higher complications risks following induction relative to post-remission therapy accounted for the main reasons for this difference ( Figure 2). 80% of centers were interested in exploring EHD after (re)induction but noted barriers including affordable local housing (71%), transportation (50%), high toxicity/infection rate (50%), high transfusion burden (50%) and limited bed availability when re-hospitalization is necessary (50%). Among the 6 centers that practice EHD, all have infusion centers with full weekday hours, 5 have full weekend/holiday hours, 3 more have evening hours, and 1 has reduced holiday/weekend hours. All can provide blood product support within 4 hours from ordering and administer IV antimicrobials within 1 hour from ordering in outpatient clinic. In 4 centers, evaluation of a patient with presumed neutropenia contacting the clinic with fever during regular hours can occur in the outpatient clinic, with subsequent admission if necessary; at one center the patient would be referred to the ED and at one center the patient would be directly admitted to an inpatient ward. If a patient needs admission, a bed would be available for direct admission to the inpatient ward in 4/6 of the centers &amp;gt;75% of the time, at 1 center 26-50% of the time, and at 1 center &amp;lt;25% of the time. EHD was not practiced at any centers in cities with population of &amp;gt;1 million, citing local housing availability as a major EHD barrier. There was no correlation between the ability to practice EHD and annual AML patient volume, treatment intensity patterns, or hospitalization practices following HCT. Conclusions: Hospitalization and care patterns following AML therapy are highly variable across major U.S. cancer institutions. While only 20% of major cancer centers surveyed practice EHD following intensive (re)induction chemotherapy, 87% do so following post-remission therapy. There is interest in exploring this approach despite medical and logistical barriers. Given potential advantages of EHD for both patients and healthcare systems, strategies to address these barriers should be explored to reduce healthcare resource utilization and improve patients' QOL.

Barriers to clinical trial enrollment among gynecologic oncology patients at a national cancer institute-designated comprehensive cancer center (2196)

Barriers to clinical trial enrollment among gynecologic oncology patients at a national cancer institute-designated comprehensive cancer center (2196)

Efficacy of BNT162b2 vaccine and its correlation with serum vitamin D in staff at the national comprehensive cancer center in slovakia.

e24037 Background: With established efficacy and safety, BNT162b2 was one of the first licensed mRNA vaccines against SARS-CoV-2. However, it is unclear whether vitamin D serum concentrations affect vaccine efficacy after three doses. Methods: This prospective, single-center study included 273 staff members (85.4% females) of the National Cancer Comprehensive Center in Slovakia. Median age of participants was 47 years (range: 22–80) and median body mass index (BMI) was 24.8 (16.3–44.6) kg/m2. The primary objective was to determine the efficacy of BNT162b2 defined as no Covid-19 disease ≥7 days after its administration. The secondary objective was to monitor IgG neutralizing antibodies and total vitamin D in serum after vaccination and test the hypothesis on correlation of total vitamin D concentrations with the vaccine efficacy. If appropriate, results were stratified by gender (males vs females) and BMI ( &lt; 30 vs ≥30 kg/m2). Results: At median follow-up of 4.7 (2.9–5.0) months, vaccine efficacy was 86.1%. The most common adverse events (AEs) were injection site pain (73.3%), fatigue (44.0%), and limb pain (33.0%). No grade 3/4 AEs were observed. Median time from vaccine administration to measurement of IgG and vitamin D concentrations was 3.4 (2.1-4.8) months. IgG concentrations were significantly higher in males compared to females, as well as in subjects with high vs low BMI ( p&lt; 0.0004 and p&lt; 0.0001, respectively). Total vitamin D concentrations were significantly lower in individuals with high vs low BMI ( p&lt; 0.0144). No differences in the rate of Covid-19 positivity were identified based on gender, BMI, and total vitamin D concentrations. Conclusions: This study confirmed high efficacy of third dose of the BNT162b2 vaccine with an acceptable safety profile. The vaccine efficacy was not affected by gender, BMI, and total vitamin D concentrations. These results suggest that serum vitamin D monitoring after third BNT162b2 dose is not beneficial for an estimation of its efficacy. This study was supported by the National Cancer Institute, Bratislava, Slovakia &amp; OncoReSearch, Rovinka, Slovakia. Keywords: BNT162b2; total vitamin D; efficacy; safety profile; IgG.

Outcomes of the facelift incisional approach to neck dissection without endoscopic or robotic assistance

<h2>Abstract</h2><h3>Objective</h3> : The facelift incisional approach to neck dissection offers several advantages including improved cosmesis, increased patient satisfaction, and decreased morbidity. This approach has been previously described using robotic or endoscopic instrumentation, but the clinical outcomes of this approach using standard instrumentation have not been reported. The objective of this study was to determine if the facelift incisional approach to neck dissection can be performed without endoscopic or robotic assistance and achieve improved oncologic and cosmetic outcomes. <h3>Study Design</h3> : Retrospective cohort study over 4 years. <h3>Setting</h3> : A national comprehensive cancer center. <h3>Methods</h3> <b>:</b> 104 subjects received 113 oncologic neck dissections, of which 35 were performed using a facelift approach. Primary outcomes included rate of negative margins, recurrence, incidence of nerve weakness, and incidence of lymphedema. <h3>Results</h3> : The mean age of the cohort was 60.1 ± 12.7 years and 72.6% were male. Mean follow up was 23.1 ± 19.1 months (p=0.21). 104 subjects (92.9%) had negative margins on final pathology, with no difference between approaches (88.2% vs 94.9% respectively, p=0.24). 34 subjects (97.1%) in the facelift group had no evidence of disease at study conclusion. There was no difference in marginal mandibular nerve weakness (p=0.10) nor shoulder weakness (p=0.59) between groups. There was no difference between post-operative lymphedema (38.2% vs 29.2% for the facelift vs standard incision groups, p=0.35). <h3>Conclusion</h3> : A facelift approach to neck dissection using standard instrumentation without robotic or endoscopic assistance achieves acceptable clinical and oncologic outcomes compared to the standard incisional approach with an additional benefit of improved cosmesis.

EBP education and skills building for leaders: An RCT to promote EBP infrastructure, process and implementation in a comprehensive cancer center.

Implementation of evidence-based practice (EBP) in healthcare remains challenging. The influence of leadership has been recognized. However, few randomized trials have tested effects of an educational and skills building intervention for leaders in clinical settings. Test effects of an EBP leadership immersion intervention on EBP attributes over time among two cohorts of leaders at a national comprehensive cancer center. A stratified, randomized, wait-list group, controlled design was conducted. Participants received the evidence-based intervention one year apart (2020, n=36; 2021, n=30) with EBP knowledge, beliefs, competencies, implementation self-efficacy, implementation behaviors, and organizational readiness measured at pre- and post-intervention, and one- and two-year follow-ups. Participants applied learnings to a specific clinical or organization priority topic. Baseline outcomes variables and demographics did not differ between cohorts except for age and years of experience. Both cohorts demonstrated significant changes in EBP attributes (except organizational readiness) post-intervention. Mixed linear modeling revealed group by time effects at 3-months for all EBP attributes except implementation behaviors and organizational readiness after the first intervention, favoring cohort 2020, with retained effects for EBP beliefs and competencies at one year. Following Cohort 2021 intervention, at 12-weeks post-intervention, implementation behaviors were significantly higher for cohort 2021. An intensive EBP intervention can increase healthcare leaders' EBP knowledge and competencies. Aligning EBP projects with organizational priorities is strategic. Follow-up with participants to retain motivation, knowledge and competencies is essential. Future research must demonstrate effects on clinical outcomes.

Total cost of care differences in National Comprehensive Cancer Center (NCCN) concordant and non-concordant patients with colon cancer.

3624 Background: National Comprehensive Cancer Network (NCCN) colon cancer treatment guidelines have been developed to standardize and improve quality of care. While studies have shown that concordance to these guidelines improves survival, little information exists regarding the impact of concordance and total cost of care (TCOC). This study aimed to evaluate the economic impact of NCCN concordance in patients with colon cancer versus those receiving non-concordant therapies. Methods: This is a retrospective study of patients throughout the United States with colon cancer at a large national Medicaid, Medicare, and commercial insurer from January 1, 2019 - December 31, 2020. NCCN regimen concordance was identified from pharmacy and medical claims and defined as concordant if the entire prescribed treatment regimen matched an NCCN regimen (Level 1 and 2a); patients not receiving an NCCN recommended regimen were deemed to be non-concordant. TCOC and its cost components were contrasted on a matched population of concordant and non-concordant patients with a ratio of 2:1. To eliminate possible selection bias and differences in baseline characteristics that could affect cost, propensity scores were developed using logistic regression and used to match patients on age, comorbidity, socioeconomic status (SES) index and treatment type (chemotherapy and radiation). Results: A total of 937 patients with colon cancer were included (Medicare n = 588; commercial fully insured n = 149; commercial self-insured n = 200). Beginning with and including the first treatment and for up to 180 days after, the TCOC in the concordant group was significantly less among Medicare patients; a reduction of 33% (a difference of $2,986, p &lt; 0.001) in TCOC per member per month (PMPM) was observed. This cost difference was driven primarily by medical chemotherapy spend as concordant patients spent 26% less (a difference of $1,160, p &lt; 0.001). Concordant patients spent 29% less PMPM than non-concordant patients (a difference of $35, p &lt; 0.001) on Evaluation and Management compared to non-concordant patients. There were no significant differences in Inpatient, Emergency Room and Radiation Oncology costs among all patients (p &gt; 0.05). No significant differences were seen in TCOC among commercial fully insured (a difference of $69, p = 0.99) and commercial self-insured (a difference of $5,413, p = 0.07) patients, likely due to smaller sample sizes. Conclusions: In this study, Medicare patients who received NCCN concordant colon cancer regimens spent significantly less in TCOC than patients receiving non-concordant regimens. These savings highlight the importance of evidence-based guidelines in treatment determinations to optimize the value of cancer care. More extensive studies are needed to assess if these findings translate to commercially insured patients and the long-term economic impact of concordance.

Total cost of care differences in National Comprehensive Cancer Center (NCCN) concordant and non-concordant breast cancer patients.

e18833 Background: National Comprehensive Cancer Network (NCCN) treatment guideline non-concordance for breast cancer treatment has higher total costs. However, a significant knowledge gap exists regarding which cost components increase in non-concordant therapies. The purpose of this study is to evaluate the total cost of care (TCOC) and cost components for breast cancer patients who received NCCNconcordant versus non-concordant therapies. Methods: This is a retrospective study of patients throughout the United States with breast cancer at a large national Medicaid, Medicare, and commercial insurer from January 1, 2019, to December 31, 2020. NCCN regimen concordance was identified from pharmacy and medical claims and defined as concordant if the entire prescribed treatment regimen matched an NCCNregimen (Level 1 and 2a); patients not receiving an NCCN recommended regimen were deemed to be non-concordant. TCOC and its cost components were contrasted on a matched population of concordant and non-concordant patients with a ratio of 2:1. To eliminate possible selection bias and differences in baseline characteristics that could affect cost, propensity scores were developed using logistic regression and used to match patients on age, comorbidity, socioeconomic status (SES) index and treatment type (chemotherapy and radiation). Results: A total of 315 patients with breast cancer were matched. Beginning with and including the first treatment and for up to 180 days after, the TCOC in the concordant group was significantly less across all lines of business (p &lt; 0.05). A reduction of 25%, 28% and 43% (a difference of $5,872, $6,946 and $3,542) in TCOC per member per month (PMPM) was observed in commercial fully insured (CFI), commercial self-insured (CSI) and Medicare patients, respectively. Provider administered chemotherapy spend was also significantly lower (p &lt; 0.05) in the concordant group, a reduction of 34%, 50% and 43% (a difference of $3,615, $6,788 and $1,879) in CFI, CSI and Medicare patients, respectively. Outpatient spend was 28% lower (a difference of $4,268, p = 0.08) in CFI patients and significantly lower (p &lt; 0.05) with reductions of 29% and 40% ($5,396 and $1,988) in CSI and Medicare patients, respectively. There were no significant differences in Inpatient and Emergency Room spend across all lines of business (p &gt; 0.05). Conclusions: In this study, there is a correlation between breast cancer patients on NCCN concordant therapies and a lower TCOC. The savings due to medical spend highlight the importance of evidence-based guidelines in treatment determinations. Further evaluation will be needed to determine cost changes in hospitalizations and emergency room visits.

Antibodies and cell immunity after vaccination with tozinameran (BNT162b2) in workers of National Comprehensive Cancer Center (NCCC) in Slovakia.

e18774 Background: Vaccination remains the leading strategy against Covid-19 worldwide. BNT 162b2 (tozinameran) belongs among first licensed vaccines with good efficacy. However, the role of monitoring both, antibodies and cell immunity after vaccination remains unclear. Methods: We conducted a 6-month prospective study involving vaccinated workers of NCCC in Slovakia who were tested for the presence of neutralizing antibodies and cell immunity after second dose of tozinameran. SARS-CoV-2 IgG antibodies were detected by the Atellica IM sCOVG, a fully automated 2-step sandwich immunoassay using indirect chemiluminescent technology. Blood samples were tested by two IGRA tests (Quantiferon RUO and CoviFeron) to assess interferon-γ (IFN-γ) responses to SARS CoV-2 spike protein antigen and nucleocapsid protein antigen. Results were stratified by gender and body mass index. P values for categorical variables were calculated using χ2 or Fishers exact test. P values for continuous variables were calculated using T test and Wilcoxon-Mann-Whitney test. Value of statistical significance was set to 0.05. Data were analyzed using SAS 9.4 software. Results: Medical records of 94 respondents (71 females) were analyzed. Mean age was 40.2 years (23 – 62 years) and mean body mass index (BMI) ± standard error of mean (SEM) was 26.4±2.7 (21.3 – 31.7). Twenty-two (23.4 %) respondents had Covid-19 before first, 5 (5.3 %) before second, and 2 (2.15 %) after second dose of vaccine (P &lt; 0.0001). IgG were tested 24.4±5.0, 50.2±12.1, and 187.9±12.8 days after second vaccination. IgG index progressively decline with corresponding values 126.81±40.34, 93.55±51.29, and 17.68±29.07 (P &lt; 0.0001). Mean time from second vaccination to cell immunity testing was 157.2±101.3 days. Forty-eight (51.1 %) of respondents had negative, 6 (6.4 %) border line, and 40 (42.6 %) positive cell immunity (P &lt; 0.0001). Conclusions: Our study confirmed the efficacy of tozinameran despite both, rapid decline of antibodies and absence of cell immunity in majority of subjects.

Prenatal genetic counseling practices regarding recommendations for cancer genetic counseling: A retrospective chart review from two academic institutions.

Prenatal and preconception genetic counselors are trained to take patient pedigrees to evaluate for potential risks for genetic conditions, including hereditary cancer syndromes. However, little research has been published on how often prenatal/preconception genetic counselors provide recommendations for cancer genetic counseling solely based on a family history of cancer. Therefore, this study sought to (a) characterize the types of cancers recognized for a cancer genetic counseling recommendation, (b) analyze appointment indications associated with discussion documentation, and (c) investigate how often National Comprehensive Cancer Center (NCCN) genetic testing criteria for Hereditary Breast and Ovarian Cancer syndrome (HBOC) and Lynch syndrome were met and how often a recommendation for cancer genetic counseling was made. A retrospective chart review and pedigree analysis were performed for prenatal/preconception genetic counseling patients with a family history of cancer seen at two academic institutions between August 10, 2019, and December 1, 2019. In the 170 charts included, a recommendation for cancer genetic counseling was documented in 40% of all genetic counseling summaries and in 59.2% of summaries when NCCN genetic testing criteria for HBOC and/or Lynch syndrome was met. Using chi-squared and logistic regression analysis, these data support that individuals were significantly more likely to receive a recommendation when NCCN genetic testing criteria were met (OR=5.01, p<.001) or when the family history contained two or more types of cancer (OR=2.24, p=.02). Overall, this study identified the NCCN genetic testing criteria for HBOC and Lynch syndrome for which recommendations for cancer genetic counseling were commonly missed. This characterization suggests that continuing education for prenatal and preconception genetic counselors on updated NCCN guidelines may be helpful for improving rates of cancer genetic counseling referrals, uptake of genetic testing, and cancer screening recommendations.

Effectiveness, Adverse Events, and Immune Response Following Double Vaccination with BNT162b2 in Staff at the National Comprehensive Cancer Center (NCCC).

Vaccination remains the leading strategy against COVID-19 worldwide. BNT162b2 is among the first licensed vaccines with high effectiveness. However, the role of antibody and cell immunity response monitoring after vaccination remains unclear. We conducted a 6-month prospective study involving the employees of NCCC in Slovakia, who were tested for IgG antibody and cell immune responses after double vaccination with BNT162b2. IgG antibodies were detected at 3, 7, and 26 weeks, respectively. At 6 months, blood samples were tested by two different interferon-γ release assays to determine responses to spike protein antigen and nucleocapsid protein antigen of the novel coronavirus. Results were stratified by gender and body mass index (BMI). Statistical significance was set at p = 0.05. The medical records of 94 respondents (71 females) were analyzed. The mean age was 40.2 years and the mean BMI was 26.4 kg/m2. At 6 months after double vaccination, effectiveness was 97.9%. The side effects of the BNT162b2 vaccine were similar after both doses, with no serious adverse events or new safety signals recorded. The IgG index declined rapidly (p < 0.0001), and 42.6% of subjects had positive and 57.4% borderline or negative immune cell response at 6 months (p < 0.0001). Both T cell activation and IgG counts were lower in morbidly obese patients when compared to some other BMI categories. This study confirmed an acceptable toxicity profile and the high efficacy of BNT162b2 despite a rapid decline of IgG level and negative cell-mediated immunity response in most subjects. An individualized approach to vaccination could be considered in morbidly obese individuals.

Analysis of Hematology and Oncology Fellowship Website Content and Diversity Representation.

Hematology and oncology (HO) lags behind all medicine subspecialties in fellows under-represented in medicine (URM) despite a growing minority patient population. Websites have been effectively used in URM recruitment. We evaluated all US HO program websites to facilitate a more informed and URM-considerate recruitment. We also performed a stratified analysis on programs affiliated with National Cancer Institute (NCI) Designated Cancer Centers, National Comprehensive Cancer Center Network (NCCN) member institutions, and ranked as a top 50 cancer hospital by US News, given their stated commitment to outreach. Websites of all 2019-2020 Accreditation Council for Graduate Medical Education-accredited HO programs were assessed for 28 informational and three diversity categories. Websites with > 70% of categories were comprehensive. Affiliation with NCI, NCCN, and US News was noted. One hundred fifty-six websites were analyzed: 20% were comprehensive and 22% had any diversity information. Inclusion of diversity content and being comprehensive were significantly associated (P = .001). NCI, NCCN, and US News ranking were significantly associated with inclusion of more information in univariate analyses (P < .001, P = .008, and P < .001, respectively). Multivariate analyses showed that US News ranking was significantly associated with more information (P = .005). Diversity-related univariate and multivariate analyses showed a significant association with US News ranking (P = .006 and P = .029, respectively). Most HO fellowship websites are not comprehensive and lack diversity content. Given COVID-19 travel restrictions limit in-person interviews, digital program presence remains an important opportunity. HO programs should offer comprehensive and inclusive websites to better inform applicants, including URM. This may increase institutional diversity and potentially improve URM representation in the HO workforce.

Safety and tolerability of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in ovarian cancer: clinical results from a phase I trial

Objectives: To demonstrate safety and tolerability of HIPEC in ovarian cancer. Methods: A phase I, single-institution feasibility study was designed to evaluate the safety and feasibility of HIPEC at time of optimal cytoreductive surgery (CRS) in ovarian cancer patients, followed by optional normothermic intraperitoneal chemotherapy, at City of Hope National Comprehensive Cancer Center (Duarte, CA). Primary endpoint of the trial was to evaluate the safety and feasibility of HIPEC at time of optimal cytoreductive surgery (CRS). Progression-free survival was a secondary end-point. Exploratory endpoints included the assessment of molecular markers in tumors. Eligibility criteria included epithelial ovarian cancer (stage III or IV), primary or recurrent, ECOG 0-1, and appropriate surgical candidates. 35 patients were enrolled between 2015 and 2019, who underwent optimal CRS (gross residual disease less than 1 cm), and received HIPEC intra-operatively with cisplatin at 75 mg/m2 for 60 minutes immediately following optimal CRS. Patients were stratified as either 1) primary disease (n=19), defined as having received HIPEC at time of interval CRS following neoadjuvant chemotherapy for primary EOC; 2) recurrent disease (n=16), defined as having received HIPEC at time of interval or upfront CRS for recurrent (salvage) EOC. Adjuvant chemotherapy was given at the discretion of the treating oncologist following HIPEC. Results: Median age was 58 years (36-74 years), with a mean BMI of 26. Primary (interval) patients represented 54% of patients, with pretreatment clinical stages III (53%) and IV (47%). Recurrent (salvage) patients represented 45.7%, with platinum-sensitive (75%) and platinum-resistant (25%). The most common histological subtype was high grade serous (69%). All primary (interval) patients underwent neoadjuvant chemotherapy (3-4 cycles) prior to interval CRS and HIPEC. The majority of recurrent patients (81%) did not receive neo-adjuvant chemotherapy. Thirty-three patients underwent closed technique and two underwent laparoscopic technique. Total mean operating time was 8.4 hours (4.6-15.3). Mean length of stay was 10 days (3-30). All patients underwent optimal cytoreduction (69% with complete R0 resection). Peritoneal carcinomatosis index (PCI) ranged 2 to 30 (median of 8). Patients with PCI /= 8 whose PFS was 12.6 (p=0.04). Time to initiation of adjuvant chemotherapy in recurrent patients was 8.4 weeks. 22.9% of the ovarian cancer cohort was gBRCA mutated. Median PFS for primary patients was 12.6 months (95% CI 6.4; NR); with median follow up of 22.1 months (95% CI 12.6, 31.5). Median PFS for recurrent patients was 18.8 months (95% CI 7.2; 28.7), with median follow up of 36.3 months (95% CI 21.1, 51.5). There were no grade 4 or 5 AEs. Anemia was the most common Grade 3 AE (43%), followed by liver dysfunction and electrolyte abnormalities. The most common AE of any grades were abdominal pain (86%), anemia (77%), and nausea (66%). Two patients (6%) had grade 3 acute kidney injury and one patient had grade 3 chronic kidney disease. Sodium thiosulfate was introduced to the trial in January 2018, following which there were no grade 1-4 acute or chronic kidney injuries. Download : Download high-res image (61KB) Download : Download full-size image Conclusions: HIPEC in ovarian cancer was well tolerated, without any grade 4 or 5 AEs. Renal toxicities were mitigated with sodium thiosulfate. Patients with a low PCI ( /= 8.