Institute Cancer Center Research Articles

Fumarate hydratase-deficient renal cell carcinoma: The real-world experience at Dana-Farber Cancer Institute and Moores Cancer Center.

e16522 Background: Fumarate hydratase (FH)-deficient renal cell carcinoma (RCC) is a rare and aggressive tumor with limited clinical trials dedicated to therapeutics for this disease. This retrospective study aimed to report a multi-center experience in the systemic treatment of FH-deficient RCC. Methods: The medical records of patients undergoing systemic therapy for advanced or metastatic FH-deficient RCC at Dana-Farber Cancer Institute and Moores Cancer Center were reviewed from 2012 to 2021. Demographic, histologic, molecular, and survival parameters were collected. Response was assessed using RECIST 1.1 criteria. A confirmative initial diagnosis of FH-RCC was made utilizing FH/2SC immunohistochemistry (n = 12) and/or the presence of an FH mutation (n = 6). The primary endpoint of this study was to characterize patients with FH-deficient RCC in the modern era. Results: 18 patients were included; median age at diagnosis was 45 (interquartile range [IQR]: 40-55) years. All patients had a Karnofsky Performance Status (KPS) ≥ 80. Among 14 patients with evaluable IMDC criteria, 1 (7.4%) had favorable-risk disease, while 10 (71.4%) and 3 (21.4%) had intermediate- and poor-risk disease, respectively. Tumors at diagnosis were stage III (n = 6, 33.3%), and IV (n = 12, 66.7%). Median time from diagnosis to the start of systemic therapy was 2.8 months. Six types of regimens were given as first-line therapy (Table). Fourteen patients (78%) developed disease progression on frontline therapy and received subsequent therapy; two patients, initially treated with an mTOR inhibitor and combined vascular endothelial growth factor (VEGF) inhibitor and immune checkpoint inhibitor (ICI), are off therapy and still under surveillance with no recurrence to date; one patient passed away while on frontline therapy; and one patient has limited follow-up. For a median follow-up of 22 months (IQR:6.4-49), the 18-month-overall survival estimate was 81% (95% confidence interval [CI]: 53%-94%) and median progression-free survival (PFS) was 6.7 months (95%CI: 5.0-17.0). Conclusions: This study shows considerable heterogeneity in the treatment for FH deficient-RCC, with disparate clinical outcomes. Dedicated trials and guidelines on the management of FH-deficient RCC are needed.[Table: see text]

Three-year outcomes and correlative analyses in patients with non–small cell lung cancer (NSCLC) and a very high PD-L1 tumor proportion score (TPS) ≥ 90% treated with first-line pembrolizumab.

9043 Background: Although 1st-line PD-1 monotherapy has improved survival in advanced NSCLC with a PD-L1 TPS ≥50%, responses occur in ̃45% of patients (pts). We previously showed that among pts treated with 1st-line pembrolizumab, clinical outcomes were significantly improved in those with a PD-L1 TPS of ≥90% compared to a TPS of 50-89%. Here, we report the 3-year survival analysis to 1st-line pembrolizumab in pts with a PD-L1 TPS ≥90% vs 50-89%, and characterize genomic and immunophenotypic differences between these PD-L1 expression groups. Methods: Pts with stage IV EGFR/ALK wild-type NSCLC and PD-L1 TPS ≥50% who received 1st-line pembrolizumab at the Dana-Farber Cancer Institute (DFCI) and Memorial Sloan Kettering Cancer Center (MSKCC), with a minimum follow-up of 3 years were included. Comprehensive tumor genomic profiling and multiplexed immunofluorescence (mIF) were performed to examine genomic and immunophenotypic correlates of very high PD-L1 expression on separate cohorts of NSCLC at the DFCI. Results: Among 396 pts, median age was 69, 53.3% were women, 90.1% had a history of tobacco use, 83.6% had a ECOG performance status of 0-1, and 28.8% had a KRAS mutation. At a median follow-up of 42.6 months, median progression-free (mPFS) and overall survival (mOS) in the entire cohort were 5.1 months, and 19.0 months, respectively. When compared to pts with a PD-L1 TPS of 50-89% (N = 252), those with PD-L1 TPS ≥90% (N = 144) had a significantly longer mPFS (6.0 vs 4.5 months, HR 0.67, p < 0.001), and longer mOS (30.2 vs 16.9 months, HR 0.66, p < 0.01). Kaplan-Meier estimates of the 3-year PFS and OS were 24.9% and 47.0% in the PD-L1 TPS ≥90% groups, and 9.4% and 27.7% in the PD-L1 TPS 50-89% group, respectively. A PD-L1 TPS ≥90% was confirmed to be an independent predictor of improved PFS (HR 0.68, p < 0.01) and OS (HR 0.67, p < 0.01) in multivariable analysis. Tumor genomic profiling from a separate cohort of 500 NSCLC samples revealed that mutations in STK11, KEAP1, FBXW7, and CTNNB1 were significantly more frequent in tumors with a PD-L1 TPS of 50-89% compared to those with a PD-L1 TPS ≥90% (q < 0.05). mIF on 91 NSCLCs identified significantly higher CD8+PD1+ T cells and PD-L1+ immune cells in tumors with PD-L1 TPS ≥90% vs 50-89% (p < 0.05). Conclusions: Pembrolizumab monotherapy continues to demonstrate a meaningful long-term survival benefit in pts with advanced NSCLC and a PD-L1 TPS ≥90%. NSCLCs with very high PD-L1 TPS may have a more favorable genomic and immunophenotypic profile. These findings have implications for treatment selection and clinical trial interpretation and design.

Association between decline of neutrophil-to-eosinophil ratio (NER) at week 6 after ipilimumab plus nivolumab initiation and improved clinical outcomes in metastatic renal cell carcinoma (mRCC).

4527 Background: Low baseline NER has been associated with improved response to immunotherapy in mRCC (PMID:34732251). The current study aimed to investigate the early decline of NER at week 6 after ipilimumab/nivolumab (ipi/nivo) initiation and treatment responses in mRCC. Methods: Retrospective chart review of ipi/nivo-treated mRCC patients at Vanderbilt-Ingram Cancer Center and Duke Cancer Institute was conducted. Landmark analysis at week 6 after ipi/nivo initiation was performed to assess the association between change in NER and clinical responses [progression-free survival (PFS)/overall survival (OS)]. Results: There were 150 mRCC patients included in the analysis: 78% had clear cell histology, 78% were IMDC intermediate/poor risk, and 74% were male. The median follow-up time was 11.9 months. After ipi/nivo initiation, the median NER decreased from 23.8 (interquartile range: 15.0-57.1) at baseline to 19.8 (10.6-40.8) at week 6; 102 (68%) patients had decreased NER. The NER at week 6 was grouped by percent change (≥ 50% decrease vs <50% decrease vs increase). In multivariable regression analysis after adjustment for age, sex, race, IMDC risk group, baseline NER, histology, prior systemic therapy, and prior nephrectomy (Table), decreased NER ≥ 50% was associated with improved PFS [adjusted hazard ratio (AHR): 0.55, p-value: 0.03] and OS (AHR: 0.38, p-value: 0.02) (Table). Stratified analysis was conducted by baseline NER [≥vs < baseline median NER (23.8)]: decreased NER ≥ 50% was associated with improved PFS (AHR: 0.46, p-value: 0.048) and OS (AHR: 0.29, p-value: 0.01) in the subgroup with high baseline NER. These associations were not observed in the subgroup with low baseline NER (p-value for PFS: 0.25; p-value for OS: 0.61). Conclusions: The decline of NER ≥50% at week 6 after ipi/nivo initiation was associated with improved PFS/OS in mRCC patients with high baseline NER. Prospective studies are warranted to validate NER change as a biomarker to predict response to ICIs in mRCC. [Table: see text]

Outcomes of single-agent PD-(L)-1 versus combination with chemotherapy in patients with PD-L1-high (≥ 50%) lung cancer.

9052 Background: Single agent PD-(L)-1 blockade (IO) and PD-(L)-1 blockade combined with chemotherapy (ChemoIO) are both standard first-line treatments for patients with PD-L1-high (≥ 50%) metastatic non-small cell lung cancer (NSCLC). These regimens have not been compared prospectively, so comparative effectiveness is unclear. It is also unknown if clinical and molecular tumor characteristics differentially associate with benefit to IO vs ChemoIO in patients with NSCLC with high PD-L1 tumor expression. Methods: All patients with metastatic NSCLC treated with IO or ChemoIO at two institutions (Memorial Sloan Kettering Cancer Center and Dana-Farber Cancer Institute) were reviewed. Patients with EGFR or ALK alterations, PD-L1 expression < 50%, treated with IO or ChemoIO in > 1st line setting were excluded. Overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were compared between the IO vs ChemoIO groups and association with clinical, pathologic, and molecular features was examined. To account for NGS panel differences, tumor mutational burden (TMB) values were harmonized using a z-score conversion as previously described (Vokes et al, 2019). Results: Of 639 patients with stage IV EGFR/ ALK wild-type NSCLC and PD-L1 ≥50% treated in the 1st line setting, 504 received IO and 135 received ChemoIO. Baseline ECOG performance status (p = 0.3), median PD-L1 % (p > 0.9) and TMB (p = 0.2) were similar between the IO and ChemoIO groups. For patients receiving IO vs ChemoIO, there was no significant difference in OS (HR 0.8, 95% CI 0.6 to 1.08; p = 0.2). Median PFS was shorter (HR 0.7, 95% CI 0.6 to 0.9; p = 0.004) and ORR was lower (40% IO vs 55% ChemoIO, p = 0.002) in the IO group. Among patients with durable responses (> 6 months), never smokers were less common in the IO group (6% vs 18%, p < 0.001), but there was no difference in PD-L1 expression, TMB, or mutational ( KRAS, STK11, or KEAP1) profile to suggest differential predictors of benefit to IO or ChemoIO. Conclusions: In patients with PD-L1 high NSCLC, there was no survival benefit associated with the addition of chemotherapy to IO. There were also no clear differences in PD-L1 expression or molecular features associated with durable response to IO vs ChemoIO. These findings have implications for treatment selection in this population.

P-283 Performance characteristics of a tumor-informed circulating tumor DNA (ctDNA) minimal residual disease (MRD) assay in stage 1-3 colorectal cancer (CRC) in clinical practice

Detection of MRD has emerged as a tool for risk stratification in patients with early stage CRC with potential implication for adjuvant therapy. Recently, the sensitivity of MRD testing for early detection of tumor recurrence/ metastasis compared with conventional imaging has been questioned. We sought to evaluate the diagnostic performance characteristics of the Signatera™ ctDNA assay in patients with stage 1-3 CRC at West Cancer Center and Research Institute (WCCRI). Patients with CRC who received ctDNA MRD testing 3-8 weeks after curative surgical resection for stage 1-3 disease from 12/2019 to 02/2022 were evaluated. Both patients with single testing and serial ctDNA assays were included. Individual chart review was performed to collect demographic information, verify diagnosis, stage, pathology, ctDNA and imaging results, and treatment course. ctDNA positivity rates were calculated and analyzed by diagnosis, stage, and clinical course. MRD results from 104 patients were available, 64 of which had sequential results. Positivity rate at initial testing was associated with stage: stage 1 0/9 pts, stage 2 5/40 (12.5%), stage 3 15/55 (27%). In the 64 patients with sequential data, conversion from negative to positive occurred in 7/50 (14%), 8/14 patients initially positive results converted to negative after adjuvant therapy, 5 of which developed ctDNA positivity in further monitoring after 3-14 months (range) with to date 4 recurrences confirmed by imaging. 27/104 patients were found to be ctDNA positive at any time point of which 2 patients were initially ctDNA negative with presence of overt disease (1 small pulmonary metastases, 1 incidentally found peritoneal nodule). In sequential ctDNA monitoring, both patients eventually showed positive ctDNA results. Only 1 patient had a false positive result at low Mean Tumor Molecule level (0.06 MTM/mL). Tumor-informed ctDNA MRD testing has very high sensitivity and specificity, but a one-time negative test result does not preclude the presence of metastatic disease, in particular with regard to pulmonary and peritoneal tumor manifestations. Prospective randomized and non-randomized studies are underway to further assess the clinical utility of ctDNA MRD testing in early stage CRC.

Mapping global oncology priorities: A survey of the directors of the NCI-designated cancer centers.

11008 Background: By 2040, an estimated 69% of all cancer deaths globally will occur in LMICs. Recognizing this, ASCO formed the Academic Global Oncology Task Force in 2017 to help formalize the global oncology (GO) field. Their recommendations included: better engagement with the National Cancer Institute (NCI) Center for Global Health (CGH), increased funding, and development of forums to highlight global cancer research and control activities. To further clarify how GO programs are defined and to better understand the perspectives and needs of cancer research leaders, CGH conducted a survey of the 71 Directors at the NCI-Designated Cancer Centers (NDCC). Methods: A 19-question survey was designed using Microsoft Forms and sent to the NDCC Directors via email. Responses were collected from July to September 2021. Two coders reviewed the qualitative responses to categorize the data into thematic areas. Analyses were conducted in Microsoft Excel. Results: Seventy of 71 (99%) NDCC Directors responded to the survey. 41 NDCCs (59%) reported dedicated GO programs or plans to create such a program within 5 years. Additionally, 16 Directors reported GO activities without a dedicated program, while 13 reported no GO activities. The Directors described GO as having high/extremely high (39%) or moderate (50%) importance relative to other priorities, across all types of NDCCs (basic, clinical, or comprehensive). Eight NDCCs (11%) described GO as a low priority or non-priority. 31 NDCCs (44%) reported dedicated funding for GO activities. Directors estimated interest in GO to be higher among junior faculty and trainees than senior and mid-career faculty. Future goals for established or developing GO programs included: recruitment of leadership, formalizing a strategic vision, establishing partnerships, and increasing the number of activities with international collaborations. Barriers noted were limited funding, limited capacity and expertise, and prioritizing the needs in domestic NDCC catchment areas. Conclusions: Despite variation across NDCCs, GO interest is strong as expressed by Center Directors. Strategic planning, increased funding, and improved collaboration within and between NDCCs were reported as necessary to strengthen GO at NDCCs. Continued leadership from ASCO, the NCI, and other international organizations can help facilitate dialogue and increase the prioritization of GO activities at NDCCs.

European LeukemiaNet Response Predicts Disease Progression but Not Thrombosis in Polycythemia Vera.

European LeukemiaNet Response Predicts Disease Progression but Not Thrombosis in Polycythemia Vera.

Clinical significance of sentinel lymph node biopsy in differentiated thyroid cancer

Differentiated thyroid cancers are the most common endocrine malignancy and include three main entities: papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), and Hürthle cell carcinoma (HCC). Papillary thyroid cancer (PTC) is the most common histologic subtype. Was to review different sentinel lymph node biopsy (SLNB) techniques in patients with differentiated thyroid cancer. We also will compare the detection rates and sensitivity of the different detection methods in these patients and assessment of feasibility and side effects of the different techniques. This study was a cross sectional study, Surgical Oncology Department of National Cancer Institute, Cairo University and Damietta Cancer Center, Ministry of Health and Population. Radionuclide technique (lymphoscintigraphy and gamma probe scanning) was successful in 94.6 % (35/37) of the patients as shown in table 4 and relation between SLN and identification by gamma probe. In the 37 patients, the intraoperative frozen biopsy indicated that 22 patients were experiencing SLN metastases, while post-operative routine pathological examination was able to diagnose three additional patients with lymph node metastases.

Supportive oncology care at home interventions: protocols for clinical trials to shift the paradigm of care for patients with cancer

BackgroundPatients with cancer often endure substantial symptoms and treatment toxicities leading to high healthcare utilization, including hospitalizations and emergency department visits, throughout the continuum of their illness. Innovative oncology care models are needed to improve patient outcomes and reduce their healthcare utilization. Using a novel hospital at home care platform, we developed a Supportive Oncology Care at Home intervention to address the needs of patients with cancer.MethodsWe are conducting three trials to delineate the role of Supportive Oncology Care at Home for patients with cancer. The Supportive Oncology Care at Home intervention includes: (1) a hospital at home care model for symptom assessment and management; (2) remote monitoring of daily patient-reported symptoms, vital signs, and body weight; and (3) structured communication with the oncology team. Our first study is a randomized controlled trial to test the efficacy of Supportive Oncology Care at Home versus standard oncology care for improving healthcare utilization, cancer treatment interruptions, and patient-reported outcomes in patients with cancer receiving definitive treatment of their cancer. Participants include adult patients with gastrointestinal and head and neck cancer, as well as lymphoma, receiving definitive treatment (e.g., treatment with curative intent). The second study is a single-arm trial assessing the feasibility and acceptability of the Supportive Oncology Care at Home intervention for hospitalized patients with advanced cancer. Eligible participants include adult patients with incurable cancer who are admitted with an unplanned hospitalization. The third study is a single-arm trial assessing the feasibility and acceptability of the Supportive Oncology Care at Home intervention to enhance the end-of-life care for patients with advanced hematologic malignancies. Eligible participants include adult patients with relapsed or refractory hematologic malignancy receiving palliative therapy or supportive care alone.DiscussionThese studies are approved by the Dana-Farber/Harvard Cancer Center Institutional Review Board and are being conducted in accordance with the Consolidated Standards of Reporting Trials statement for non-pharmacological trials. This work has the potential to transform the paradigm of care for patients with cancer by providing them with the necessary support at home to improve their health outcomes and care delivery.Trial registrationsNCT04544046, NCT04637035, NCT04690205.

Patient Perspectives of the Implementation of a Prostate Cancer Survivorship Clinic: A Pilot Qualitative Analysis

ABSTRACT Introduction With almost 17 million prostate cancer survivors in the United States, survivorship is becoming a significant phase of the disease state. While research on prostate cancer survivorship is expanding, a qualitative understanding of life with and after prostate cancer remains understudied. Due to the long horizon-time of prostate cancer complications and treatment side effects, a clear understanding of the patient experience, and the perceived value of survivorship care, is essential to implementing a successful patient-centered survivorship program. Objective To explore the patient-perceived role and value of a newly created prostate cancer survivorship clinic with the goal of implementing feedback to improve the survivorship clinic experience and maximizing its benefit. Methods Demographic data were collected on prostate cancer patients who underwent a robotic-assisted laparoscopic prostatectomy (RALP) during a 6-month period from September 2020 through February 2021. Phone interviews were conducted by a single researcher on a sample of eleven survivorship clinic patients. Conversations were recorded and inductive thematic analysis was used to identify patient perceptions, values and goals regarding the survivorship experience. The survivorship clinic was established as a part of our institution's cancer center and is staffed by an experienced oncology nurse practitioner, trained in both prostate cancer-specific care and survivorship care in general. Results Of the 174 men who underwent a RALP from September 2020 through February 2021, 118 (67.8%) were enrolled in the Prostate Cancer Survivorship Clinic. Ninety-eight of 118 (83.1%) patients attended at least 1 clinic appointment and 20 (16.9%) attended 2 appointments at the time of our implementation analysis. Median age of interviewed patients was 62 years (IQR 57-67.5). Median time from RALP to the most recent survivorship clinic appointment for interviewed patients was 42 days (IQR 42-43.5). Three primary themes were identified through this analysis: the value of the survivorship clinic in personalizing prostate cancer follow-up, the role of the survivorship clinic as a conveyer of information, and the focus of patients on sexual function as a marker of normalcy in survivorship. A majority of men referred to their survivorship clinic provider and the survivorship program interchangeably and cited the relationship with their provider as a key value of the survivorship clinic experience. Men viewed the role of the clinic to be a source of personalized information about prostate cancer and the recovery process and felt that survivorship clinic appointments were the appropriate place to ask follow-up questions that they perceived as “time-wasting” in their surgery appointments. Patients overwhelmingly identified sexual functional recovery as a priority in the survivorship process and often remarked on it as a surrogate marker of overall recovery. Conclusions Prostate cancer survivorship programs are essential given the life expectancy of men following prostate cancer treatment. Patient needs and survivorship goals should drive expansion and improvement of survivorship programs and focus on personal relationship building, targeting and personalization of information dissemination and sexual functional recovery. This pilot justifies an expanded qualitative analysis to better characterize the patient-perceived value of survivorship clinics. Disclosure No

A longevity society requires integrated palliative care models for historically excluded older people

A longevity society requires integrated palliative care models for historically excluded older people

Closing the global pain divide: balancing access and excess

Closing the global pain divide: balancing access and excess

Confocal Microscopy and its Role in Teledermatology: Diagnosis of Basal Cell Carcinoma in a Clinical Setting

Background Reflectance confocal microscopy (RCM) is a noninvasive tool that is used to diagnose skin cancers. However, RCM requires an expert consultation, which is often performed via store-and-forward (SAF) teledermatology. Unfortunately, SAF does not mimic bedside diagnosis, nor permits interaction between the remote expert reader, physician, and patient. Recently, a live interactive method (LIM)–tele-RCM approach was shown to diagnose basal cell carcinoma (BCC) from a remote location, demonstrating advantages over SAF by providing a bedside diagnosis during consultation. Objective The aim of this study is to validate the LIM-tele-RCM approach to diagnose BCC in a real-world setting. Methods In this pilot study, 4 patients with 6 clinically suspicious BCC lesions were enrolled and imaged with RCM at a Los Angeles dermatology clinic. A Health Insurance Portability and Accountability Act–compliant teleconferencing application was used to livestream RCM images to an expert RCM reader in New York. The expert reader had remote control of the software, direct audio communication with the clinic, and the patient’s clinical history with dermoscopy. During imaging, RCM features were noted, and a diagnosis was made at the bedside. After imaging, patients completed a short questionnaire (on a 5-point scale, with 5 being the highest score) about satisfaction, comfort, and communication during the session. Results RCM diagnosed 4/6 (67%) lesions correctly as BCC and 2/6 (33%) were false-positive diagnoses. The true-positive lesions had “tumor islands with palisading and clefting” and were directly managed with Mohs surgery. The false-positive lesions had “dark silhouettes” (a common false-positive feature for BCC) and underwent a shave biopsy for confirmation. The entire session ranged from 15 to 20 minutes (an average of 17.7 minutes), comparable to the reported RCM procedure time. On the questionnaire, all patients responded with the highest rating (5/5) for each question. Conclusions LIM-tele-RCM demonstrates potential advantages over the SAF method, enabling bedside diagnosis with similar diagnostic accuracy as reported in the literature and proper management. Additionally, the remote reader had access to patients’ clinical backgrounds and could engage with patients. It may also be useful for training novice RCM users and beneficial in settings where remote diagnostics are desired, such as during the COVID-19 pandemic. However, technical challenges such as image quality degradation during video streaming, poor internet bandwidth, and end user latency may impact diagnosis. Larger, multicenter studies are needed to assess the accuracy of LIM-tele-RCM for the diagnosis of BCC and other neoplastic and inflammatory lesions, and to quantify technical limitations. Acknowledgments This work was funded by the National Cancer Institute Cancer Center (Grant P30 CA008748). Conflicts of Interest None declared.

Abstract OT1-18-04: A phase II study of dual immune checkpoint blockade (ICB) plus bicalutamide to enhance thymic T-cell production and immunotherapy response in metastatic breast cancer (MBC)

Abstract Background: The addition of anti-programmed death 1/ligand 1 (anti-PD-1/L1) improves progression-free survival when combined with chemotherapy in PD-L1-positive triple-negative MBC. However, novel combination therapies are needed to improve efficacy in hormone receptor positive (HR+) MBC, or in patients with PD-L1-negative disease. Dual ICB with nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) has not been studied in depth in MBC despite its success in other solid tumors. Furthermore, MBCs often express the androgen receptor (AR), which can be targeted therapeutically. AR blockade agents have been shown to stimulate thymic production of naïve T-cell clones. It is proposed that ICB in conjunction with AR blockade may facilitate thymopoeisis and subsequent activation of novel, tumor-reactive T-cell clones. Trial design: This is a phase II, open-label trial investigating the combination of ICB (nivolumab 240mg IV q2w; ipilimumab 1mg/kg IV q6w) and AR blockade (bicalutamide, 150mg PO daily) in MBC. Two cohorts will be studied: AR-positive TNBC [ > 1% by IHC, constituting ~50% of TNBCs]; and HR+ MBC (of which the great majority are AR-positive). Eligibility: Patients must have RECIST1.1 measurable disease, ECOG performance score 0-1, and adequate hematological and hepatic function. Subjects may have received no more than 1 prior non-curative chemotherapy. Specific aims: Subjects will be assessed for clinical benefit by iRECIST criteria and safety by CTCAE v4.0, with clinical efficacy defined as >20% improvement in week 24 clinical benefit rate, over historical control (30% per EMBRACE clinical trial). Statistical analysis will be performed by a Simon 2-stage design to minimize futility (n = 46/cohort, stage I: n = 15). As exploratory aims, thymic generation of T-cells will be measured via quantitative deep sequencing of T-cell receptors (TcR, ImmunoSEQ assay), TcR excision circles (TRECs), and flow cytometry using markers of recent thymic emigration. Present accrual: As of 7/8/2021, n=19 subjects are enrolled (4 TNBC, 15 HR+). The trial is open at Providence Cancer Institute (Portland, OR) and Memorial Sloan Kettering Cancer Center (New York, NY). Target accrual: stage I: n=15 per arm; a maximum of 138 patients (46 per cohort) may be enrolled in expansion cohorts. Contact: Dr. David Page (David.page2@providence.org) Clinicaltrials.gov#: NCT03650894 Citation Format: David B Page, Krystle L Collins, Brie Chun, Zhaoyu Sun, William L Redmond, Maritza Martel, Yaping Wu, Nicole Moxon, Staci L Mellinger, Walter J Urba, Tiffany A Traina, Ayca Gucalp. A phase II study of dual immune checkpoint blockade (ICB) plus bicalutamide to enhance thymic T-cell production and immunotherapy response in metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-18-04.

Abstract P2-15-02: Using Oncotype DX Breast Recurrence Score® (RS) assay to define the role of neoadjuvant endocrine therapy (NET) in early-stage hormone receptor positive (HR+) breast cancer (BC)

Abstract Background:Adjuvant endocrine therapy remains the standard of care for patients (pts) with early stage, HR+ BC who can safely omit chemotherapy based on RS results; however, the role of NET remains unclear. There are limited data regarding the optimal duration of treatment with NET and the ideal patient (pt) population for NET in terms of age and RS result. This question rose to critical importance amidst the COVID-19 pandemic, during which NET was utilized more broadly in attempts to delay surgery or chemotherapy while preserving optimal pt outcomes. This study re-examines the use of NET among a cohort of pts with HR+ BC randomized to NET or neoadjuvant chemotherapy (NCT) based on RS (performed on initial core biopsy specimens).Methods:Data were pooled from two independent studies performed at Emory’s Winship Cancer Institute and Massey Cancer Center at Virginia Commonwealth University (VCU) from 2010-2012. These studies evaluated rates of clinical and pathologic complete response (pCR) among pts with early stage, HR+ BC assigned to treatment groups based on RS results. Pts with RS 0-10 received NET (Group (Grp) A), RS 11-24/25 (Emory 11-24 vs VCU 11-25) were randomized to NET (Grp B) or NCT (Grp C), and those with RS 25/26-100 received NCT (Grp D). Associations between RS result, neoadjuvant therapy and pCR in the breast, lymph nodes (LN) and breast plus LN were evaluated using Fisher’s exact test. Results:109 pts were included in this analysis. The Emory cohort was younger (median age 56 years (yrs) vs 63 yrs in VCU cohort) and more diverse (37.5% African American (AA) vs 18.6% AA in VCU cohort). The pts were predominantly post-menopausal (69.6% Emory vs 83.1% VCU). Nodal status among the Emory cohort was evenly divided with 50% N0 and 50% N+, while the majority of VCU pts were N0 (76.3% N0 vs 22.0% N+). Pts were grouped based on RS result: RS <11 (18% Emory vs 20.3% VCU), RS 11-24/25 (36% Emory vs 55.9% VCU) and RS 24/25 or higher (46% Emory vs 23.7% VCU). Pts with low RS result were older (median 64 yrs vs 59 yrs among RS > 24/25) with higher percentage of low-grade tumors (47.6% grade 1 vs 5.4% grade 1 among RS >24/25). With regard to pCR, there were no significant differences among pts with low or intermediate RS results, as no pts in these groups achieved pCR in the breast or breast + LN (Table). Pts with RS result 25/26-100 (Grp D) were the only pts shown to achieve pCR in breast + LN (18.9%, p= 0.0043 across groups). Notably, while pts on the Emory study received longer courses of NET (median 10 months vs 5.5 months), there were no significant differences in pCR across RS result subgroups noted between the two institutions. Conclusion:Our results demonstrate that the use of Oncotype DX Breast Recurrence Score® or other genomic assays in the neoadjuvant setting may help guide treatment decisions when considering the use of NET versus NCT. Pt age and length of endocrine therapy as well as pt preferences should be considered when determining neoadjuvant treatment plans. There are currently ongoing studies evaluating the use of NET with CDK4/6 inhibitors that will offer further insight into optimal neoadjuvant treatment strategies in HR+ BC. Subsequent phase III evaluation of the role of genomic assays in the neoadjuvant setting is feasible and may help determine whether NET + CDK 4/6 inhibitors could replace NCT for pts with higher RS values. Table: pCR according to treatment groups (All Eligible Patients)VariableGroup A (N=21)Group B (N=23)Group C (N=22)Group D (N=37)P value (a)pCR Breast0 (0.0%)0 (0.0%)0 (0.0%)8 (21.6%)0.0016pCR Nodes0 (0.0%)1 (4.3%)3 (13.6%)2 (5.6%)0.2977pCR Breast + Nodes0 (0.0%)0 (0.0%)0 (0.0%)7 (18.9%)0.0043(a) Fisher's exact test was used for categorical variables with cell counts <5.Note: Group A= Recurrence Score <11,Group B= Recurrence Score 11-24 (Emory study) or 11-25 (VCUstudy) receiving NET,Group C= Recurrence Score 11-24 (Emory study) or 11-25 (VCUstudy) receiving NCT,and Group D= Recurrence Score >24 (Emory study) or >25 (VCUstudy).Note: 1 patient did not receive SLNB(sentinel lymph node biopsy) or ALND (axillary lymph node dissection) and is excluded from the denominator for pCR Nodes. Citation Format: Caitlin Taylor, Aimee Foreman, Christy Russell, Dipankar Bandyopdhyay, Xiaoyan Deng, Lisa Floyd, Amelia Zelnak, Ruth O'Regan, Harry Bear, Jane Meisel. Using Oncotype DX Breast Recurrence Score® (RS) assay to define the role of neoadjuvant endocrine therapy (NET) in early-stage hormone receptor positive (HR+) breast cancer (BC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-15-02.

Geriatric risk factors for serious COVID-19 outcomes among older adults with cancer: a cohort study from the COVID-19 and Cancer Consortium

BackgroundOlder age is associated with poorer outcomes of SARS-CoV-2 infection, although the heterogeneity of ageing results in some older adults being at greater risk than others. The objective of this study was to quantify the association of a novel geriatric risk index, comprising age, modified Charlson comorbidity index, and Eastern Cooperative Oncology Group performance status, with COVID-19 severity and 30-day mortality among older adults with cancer.MethodsIn this cohort study, we enrolled patients aged 60 years and older with a current or previous cancer diagnosis (excluding those with non-invasive cancers and premalignant or non-malignant conditions) and a current or previous laboratory-confirmed COVID-19 diagnosis who reported to the COVID-19 and Cancer Consortium (CCC19) multinational, multicentre, registry between March 17, 2020, and June 6, 2021. Patients were also excluded for unknown age, missing data resulting in unknown geriatric risk measure, inadequate data quality, or incomplete follow-up resulting in unknown COVID-19 severity. The exposure of interest was the CCC19 geriatric risk index. The primary outcome was COVID-19 severity and the secondary outcome was 30-day all-cause mortality; both were assessed in the full dataset. Adjusted odds ratios (ORs) and 95% CIs were estimated from ordinal and binary logistic regression models.Findings5671 patients with cancer and COVID-19 were included in the analysis. Median follow-up time was 56 days (IQR 22–120), and median age was 72 years (IQR 66–79). The CCC19 geriatric risk index identified 2365 (41·7%) patients as standard risk, 2217 (39·1%) patients as intermediate risk, and 1089 (19·2%) as high risk. 36 (0·6%) patients were excluded due to non-calculable geriatric risk index. Compared with standard-risk patients, high-risk patients had significantly higher COVID-19 severity (adjusted OR 7·24; 95% CI 6·20–8·45). 920 (16·2%) of 5671 patients died within 30 days of a COVID-19 diagnosis, including 161 (6·8%) of 2365 standard-risk patients, 409 (18·5%) of 2217 intermediate-risk patients, and 350 (32·1%) of 1089 high-risk patients. High-risk patients had higher adjusted odds of 30-day mortality (adjusted OR 10·7; 95% CI 8·54–13·5) than standard-risk patients.InterpretationThe CCC19 geriatric risk index was strongly associated with COVID-19 severity and 30-day mortality. Our CCC19 geriatric risk index, based on readily available clinical factors, might provide clinicians with an easy-to-use risk stratification method to identify older adults most at risk for severe COVID-19 as well as mortality.FundingUS National Institutes of Health National Cancer Institute Cancer Center.

Study protocol for a randomised trial evaluating the non-inferiority of stepped palliative care versus early integrated palliative care for patients with advanced lung cancer

IntroductionIntegrating palliative care (PC) early in the illness course for patients with serious cancers improves their outcomes and is recommended by national organisations such as the American Society of Clinical...

Randomized Waitlist-Control Trial of a Web-Based Stress-Management and Resiliency Program for Adolescent and Young Adult Cancer Survivors: Protocol for the Bounce Back Study.

BackgroundThe emotional health of adolescent and young adult (AYA) cancer survivors is compromised both during and after cancer treatment. Targeted programs designed to support AYAs’ ability to cope with stress in the years following treatment completion are lacking. Mind-body programs may ameliorate the negative psychological and emotional effects of stress and assist AYAs with managing the psychosocial challenges of early survivorship.ObjectiveOur randomized waitlist-control trial aims to assess the feasibility, acceptability, and preliminary efficacy of a virtual group program (Bounce Back) to promote stress management and resiliency among posttreatment AYAs.MethodsBounce Back is a stress management and resiliency program delivered via videoconference by a trained mental health clinician. Sessions were adapted from an evidence-based mind-body program (Stress Management and Resiliency Training - Relaxation Response Resiliency Program [SMART-3RP]) grounded in relaxation response elicitation, mindfulness, cognitive behavioral therapy, and positive psychology. Seventy-two AYAs (diagnosed with cancer between ages 14 years and 29 years and had completed cancer treatment within the last 5 years) were randomly assigned to the Bounce Back program or waitlist-control group and completed assessments at baseline, 3 months postbaseline, and 6 months postbaseline. The primary aim of the study is to determine the feasibility and acceptability of the Bounce Back program. Descriptive statistics, including means, frequencies, and ranges supplemented by qualitative exit interview feedback will be used to characterize the sample and to summarize feasibility and acceptability. The exploratory aims are to evaluate the preliminary effects of the program on stress coping and psychosocial outcome measures (ie, anxiety, depression) collected across the 3 time points.ResultsThis study was funded by the National Cancer Institute in July 2017. Study procedures were approved by the Dana-Farber Harvard Cancer Center Institutional Review Board in October 2018 (Protocol 18-428). The randomized trial was conducted from July 2019 to March 2021. Quantitative data collection is complete, and qualitative exit interview data collection is ongoing. Results are expected to be published in peer-reviewed journals and presented at local, national, or international meetings in the coming years.ConclusionsFew evidence-based programs exist that tackle the key transitional issues faced by AYA cancer survivors. Future analyses will help us determine the feasibility and acceptability of the Bounce Back program and its impact on AYA stress coping and psychological well-being.Trial RegistrationClinicalTrials.gov NCT03768336; https://clinicaltrials.gov/ct2/show/NCT03768336International Registered Report Identifier (IRRID)DERR1-10.2196/34033

Abstract PO-211: 2020 Impact on research productivity survey: The Geographic Management of Cancer Health Disparities Program (GMaP) regional response

Abstract Purpose: The Geographic Management of Cancer Health Disparities Program is a national program funded by the National Cancer Institute's Center to Reduce Cancer Health Disparities (CRCHD). The seven GMaP regions use a multipronged engagement approach to increase recruitment/retention of diverse investigators and to strengthen professional development. This survey was designed to assess if and how the events of 2020 (COVID, racial or political unrest, others) impacted current research productivity, applications for future funding, and publication submission. Methods: A REDCap survey was sent out to each of the GMaP regional listservs in October 2020 and was completed by 150 researchers by early stage (71, 50.0%) and established investigators (36, 25.4%). Half (51%) identified as a non-white race, and 17.8% identifying as Hispanic or Latino. 22.7% of respondents were from Region 4. Responses were recorded via 6 point Likert scale (No Impact, Minimal, Neutral, Significant Impact, Work Stoppage, Expanded Scope) and allowed for qualitative responses. Summary of Results for Region 4: More than half stated the pandemic created “Significant or Work Stoppage” on their current research. Only 11.8% were able to submit intended publications on time. Only 21.2% still planned to submit applications for future funding on their intended timeline. Systemic racism/social unrest was identified as Significant Impact to 50%, along with 47.1% by local/national politics. Qualitative responses provided profound examples of the difficulties researchers have experienced in 2020. Respondents indicated that pilot awards (76.7%) and research support awards (40%) are the best methods to support their career development. Recommendations: The GMaP network with its regional approach is well placed to continue to support the career development needs of their researchers. GMaP opened their trainings to virtual national audiences, and adapted travel award programs to provide smaller Research Support awards (21 awarded) and larger Pilot Awards (4 awarded). GMaP shared the stories of their members with NCI, and advocated for support. These data further inform and enhance specific GMaP program offerings, and help us better advocate for our researchers at the institutional and national level. Citation Format: Carrie Norbeck, Linda Fleisher. 2020 Impact on research productivity survey: The Geographic Management of Cancer Health Disparities Program (GMaP) regional response [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-211.

Abstract PO-174: Using GIS mapping to explore factors in Texas' disparities in access to cancer care

Abstract Introduction: The significant decline in cancer incidence and mortality over the last two decades in the United States is likely the result of reductions in tobacco use, increased uptake of preventive methods, adoption of early screening methods and improved treatment options. Texas, due to its large size and significant rural and heterogeneous populations, continues to experience disparities in cancer incidence and access to care and clinical trials. This study aimed to: 1) assess cancer incidence in Texas for three target indications compared to national data, and 2) analyze potential disparities in access to care with respect to the locations of American College of Surgeons Accredited (ACoS) Cancer Centers and National Cancer Institute (NCI) Cancer Centers within Texas' 11 Public Health Regions (PHR). Methods: We used data from the Texas Cancer Registry and compared age-adjusted incidence for our three target indications (adult colon cancer in patients under 50 years of age, advanced cervical cancer, and advanced liver cancer) in the 11 PHR and the defined Border Region of Texas with national data from the US Surveillance, Epidemiology, and End Results Program (SEER). We used GIS mapping to locate the cancer centers in Texas' PHR. Results: Initial results indicate that all 11 Texas' PHR ranked higher than national averages for age-adjusted incidence of cervical and liver cancer. Further, incidence rates for adolescents and young adult colorectal cancer are above SEER average in the majority of the PHR located in the northern and eastern regions of the state. When compared with Texas incidence rates, PHR 1 (Lubbock) and PHR 11 (Harlingen) have higher incidence rates for all three indications. Two PHR in the Border region (PHR 10: El Paso and 11: Harlingen) have Texas' highest incidence of liver cancer. The distribution of ACoS centers appears concentrated in eastern Texas, with highest numbers in PHR 3 (Dallas area) and PHR 6 (Houston area); with three of the four NCI-designated cancer centers in Texas are located in these two regions. Lower rates of cancer incidence for all three cancer indications were found in PHR regions 3 and 6. Among the Border counties, Cameron, Maverick and Star counties ranked above the Texas' average for all three cancer indications. There is an apparent paucity of cancer centers in the Border Region with only three centers identified in the 32 counties within the region. Conclusion: Texas statewide ranked above SEER's averages in two of the three cancer indications-cervical and liver cancers. There are clear regional differences in incidence of cervical, liver, and colorectal cancer which suggest disparities in access to care. Future research will draw on these findings to assess distance to cancer centers and clinical trial locations for Texas patients in our three targeted cancers and determine if broadband coverage is associated with disparities in cancer rates. Citation Format: Yeka W. Nmadu, Deborah V. Dahlke, Scott A. Horel, Marcia G. Ory, Kenneth S. Ramos. Using GIS mapping to explore factors in Texas' disparities in access to cancer care [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-174.