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Large analyses of T4 larynx cancer (LC) have raised concerns that larynx preservation (LP) contributes to reduced survival compared with laryngectomy (LGX). The role of operability has not been previously considered as a confounder.We queried the National Cancer Database for T4M0 LC diagnosed 2004-2015. Patients were categorized as undergoing LGX, chemoradiotherapy but operable (LP-operable), and chemoradiotherapy inoperable (LP-inoperable). Overall survival (OS) was estimated by Kaplan-Meier. Cox multivariate analysis (MVA) identified variables associated with OS.We identified 1405 LGX, 164 LP-operable and 1969 LP-inoperable patients. Compared with LGX, MVA demonstrated worse OS among LP-inoperable (HR 1.28 95%CI 1.17-1.40, p 0.01) but not LP-operable patients (HR 1.12 95%CI 0.91-1.39, p = 0.28).LP-operable patients did not have significantly worse OS than those undergoing LGX.

BACKGROUND: Hepatic epithelioid hemangioendothelioma (HEH) is a rare vascular tumor of unknown etiology and unpredictable natural history. To date, no large-scale studies have been published evaluating this disease due to its rare occurrence. METHODS: The National Cancer Database was reviewed between 2004 and 2016 to identify patients with HEH. Univariate analysis with overall survival (OS) was performed by Cox proportional hazards model. Kaplan–Meier method was used to create OS curves and compared using the log-rank test. RESULTS: We identified 229 patients with HEH. The majority of patients were female (61.1%), white (84.3%), and had a Charlson–Deyo score of 0 (75%). Chemotherapeutic intervention was seen in 26% of the patients while 33% received surgical intervention in the form of wedge/segmental liver resection (n = 27), hepatectomy lobectomy/extended lobectomy (n = 18), and liver transplant (n = 22). Five-year survival in surgical patients was 90.5%, 66.5% and 81%, respectively (p = 0.485). Age greater than 55 years (hazard ratio [HR], 2.78; p < 0.001), Asian ethnicity compared to white (HR, 2.84; p = 0.012), and a higher Charlson–Deyo score (score 1: HR, 2.28; p < 0.001 and score ≥2: HR, 2.76; p = 0.011) were associated with worse OS. CONCLUSION: Treatment for HEH remains variable with only a third of the patients undergoing surgery. International collaboration is necessary to determine the optimal treatment for this rare disease.

Purpose: Biliary tract cancers (BTC) are aggressive malignancies refractory to chemotherapy and immunotherapy. MEK inhibition (MEKi)-based regimens may have utility in this disease when combined with PD-L1 blockade. We hypothesize that dual MEK/PD-L1 inhibition alters circulating soluble and cellular immune mediators to improve clinical outcomes in patients with advanced BTC. Experimental Design: We examined immune features in peripheral blood from 77 patients with advanced BTC enrolled in a phase II clinical trial investigating atezolizumab with or without cobimetinib. Plasma and peripheral blood mononuclear cells (PBMC) were isolated from whole blood to evaluate soluble factors and immune cell populations. Baseline blood samples were additionally compared with healthy donors to identify immune signatures unique to BTC. Results: At baseline, the soluble factors platelet-derived growth factor B (PDGF)-BB, placental growth factor (PlGF)-1, IL5, and IL17A were elevated in patients with BTC compared with healthy adult donors, and higher baseline frequencies of CD8+BTLA+ T cells correlated with better overall survival (OS) in this trial. There were also significant treatment-related alterations in several factors, including decreased PDGF-BB following combination treatment, that correlated with improved OS and progression-free survival (PFS). Higher baseline levels of IL23 and RANTES corresponded to improved clinical outcomes following combination treatment. Dual MEK/PD-L1 inhibition increased populations of CD4+TIM3+ and decreased CD8+VISTA+ T cells, correlating with worse OS and better PFS, respectively. Conclusions: This work represents a comprehensive analysis of peripheral immune features in patients with BTC and systemic responses to dual MEK/PD-L1 inhibition. These data support further investigation to understand how MEKi combines with immunotherapeutic approaches to improve clinical outcomes for patients with advanced BTC.

Melphalan is an alkylating agent used in both autologous (ASCT) and allogeneic stem cell transplantation. It is a substrate of L-type amino acid transporter-1 (LAT-1) and LAT-2, which are involved in its tissue penetration and elimination. Gabapentin and pregabalin, common concomitant medications in patients with multiple myeloma undergoing ASCT, are also substrates of LAT transporters, raising concern for potential competitive inhibition of melphalan transport. We evaluated whether concurrent use of gabapentin or pregabalin in patients receiving high-dose melphalan (≥140 mg/mWe aimed to determine if concurrent administration of gabapentin or pregabalin and melphalan increased melphalan toxicity.This was a single-center, retrospective evaluation including patients ≥18 years of age who received high-dose melphalan as part of a conditioning regimen at the Winship Cancer Institute of Emory University between August 1, 2010 and April 1, 2020 and were followed through their transplant admission. After identification and inclusion of patients who received melphalan in combination with gabapentin or pregabalin, patient matching based on age (±5 years), sex, and melphalan dose (140 mg/mAmong 176 patients evaluated in each group, median hospital LOS was 16 days, median time to neutrophil engraftment was 14 days, and median time to platelet-20 engraftment was 16 days in both groups. In addition, there were no significant differences in supportive care requirements between groups.In this study, use of gabapentin or pregabalin in combination with melphalan did not impact safety of the conditioning regimen in patients undergoing ASCT.

Neoadjuvant chemotherapy (NAC) is increasingly used for operable breast cancer (BC). Appropriate radiation therapy (RT) fields (ie, whole breast [WB] ± regional nodal irradiation [RNI]) in patients who were clinically node positive (cN1) but convert to pathologically node negative (ypN0) after NAC are unknown and the subject of the accruing NSABP B-51 trial. We sought to compare outcomes between WB RT with or without RNI following breast conservation and sentinel lymph node biopsy (SLNB) alone in cN1, ypN0 women following NAC.We identified all BC patients with cN1, ypN0 who underwent NAC followed by lumpectomy and SLNB between 2006 and 2015 in the National Cancer Database. RNI utilization was evaluated using Cochran-Armitage test. Overall survival between WB RT alone versus WB + RNI was compared using Kaplan-Meier with and without propensity score-based weighted adjustment and multivariable (MVA) Cox proportional hazards.From 2006 to 2015, RNI use increased from 48.13% to 62.13% (Pfor trend.001). The 10-year survival for WB alone versus WB + RNI was 83.6% and 79.5%, respectively (P= .14). On MVA analysis, the addition of RNI compared to WB alone was not associated with a survival benefit (WB vs. WB + RNI: hazard ratio 0.80, 95% confidence interval, 0.58-1.11, P= .19). Results were unchanged after propensity score-based adjustment.For women with cN1 BC who convert to ypN0 following NAC and breast conserving surgery with SLNB alone, more extensive RNI may not provide a long-term survival benefit. Prospective validation via the NSABP B-51 trial will be essential.

Supplementary Table from Combined MEK/PD-L1 Inhibition Alters Peripheral Cytokines and Lymphocyte Populations Correlating with Improved Clinical Outcomes in Advanced Biliary Tract Cancer

Supplementary Figure from Combined MEK/PD-L1 Inhibition Alters Peripheral Cytokines and Lymphocyte Populations Correlating with Improved Clinical Outcomes in Advanced Biliary Tract Cancer

Purpose:Biliary tract cancers (BTC) are aggressive malignancies refractory to chemotherapy and immunotherapy. MEK inhibition (MEKi)-based regimens may have utility in this disease when combined with PD-L1 blockade. We hypothesize that dual MEK/PD-L1 inhibition alters circulating soluble and cellular immune mediators to improve clinical outcomes in patients with advanced BTC.Experimental Design:We examined immune features in peripheral blood from 77 patients with advanced BTC enrolled in a phase II clinical trial investigating atezolizumab with or without cobimetinib. Plasma and peripheral blood mononuclear cells (PBMC) were isolated from whole blood to evaluate soluble factors and immune cell populations. Baseline blood samples were additionally compared with healthy donors to identify immune signatures unique to BTC.Results:At baseline, the soluble factors platelet-derived growth factor B (PDGF)-BB, placental growth factor (PlGF)-1, IL5, and IL17A were elevated in patients with BTC compared with healthy adult donors, and higher baseline frequencies of CD8+BTLA+ T cells correlated with better overall survival (OS) in this trial. There were also significant treatment-related alterations in several factors, including decreased PDGF-BB following combination treatment, that correlated with improved OS and progression-free survival (PFS). Higher baseline levels of IL23 and RANTES corresponded to improved clinical outcomes following combination treatment. Dual MEK/PD-L1 inhibition increased populations of CD4+TIM3+ and decreased CD8+VISTA+ T cells, correlating with worse OS and better PFS, respectively.Conclusions:This work represents a comprehensive analysis of peripheral immune features in patients with BTC and systemic responses to dual MEK/PD-L1 inhibition. These data support further investigation to understand how MEKi combines with immunotherapeutic approaches to improve clinical outcomes for patients with advanced BTC.

The CD8+ T-cell response is prognostic for survival outcomes in several tumor types. However, whether this extends to tumors in the brain, an organ with barriers to T cell entry, remains unclear. Here, we analyzed immune infiltration in 67 brain metastasis (BrM) and found high frequencies of PD1+ TCF1+ stem-like CD8+ T-cells and TCF1- effector-like cells. Importantly, the stem-like cells aggregate with antigen presenting cells in immune niches, and niches were prognostic for local disease control. Standard of care for BrM is resection followed by stereotactic radiosurgery (SRS), so to determine SRS’s impact on the BrM immune response, we examined 76 BrM treated with pre-operative SRS (pSRS). pSRS acutely reduced CD8+ T cells at 3 days. However, CD8+ T cells rebounded by day 6, driven by increased frequency of effector-like cells. This suggests that the immune response in BrM can be regenerated rapidly, likely by the local TCF1+ stem-like population.

To report the activity of venetoclax in patients with relapsed mantle cell lymphoma (MCL), we identified 81 patients treated with venetoclax monotherapy (n=50, 62%) or in combination with a BTK inhibitor (n=16, 20%), an anti-CD20 monoclonal antibody (n=11, 14%), or others at 12 US academic medical centers. Patients had high-risk disease features including Ki67 >30% (61%), blastoid/pleomorphic histology (29%), complex karyotype (34%), and TP53 alterations (49%), and received a median of 3 prior treatments including BTK inhibitors in 91%. Venetoclax alone or in combination resulted in an overall response rate (ORR) of 40% and median progression-free (PFS) and overall survival (OS) of 3.7 and 12.5 months, respectively. The receipt of ≤ 3 prior treatments was associated with higher odds of response to venetoclax in a univariable analysis. In a multivariable analysis, having a high-risk MIPI score prior to venetoclax and disease relapse or progression within 24 months of diagnosis were associated with inferior OS whereas the use of venetoclax in combination was associated with superior OS. Although most patients (61%) had low risk for tumor lysis syndrome (TLS), 12.3% of patients developed TLS despite the implementation of several mitigation strategies. In conclusion, venetoclax resulted in good ORR but short PFS in high-risk patients with MCL and may have a better role in earlier lines of treatment and/or in combination with other active agents. TLS remains an important risk in patients with MCL who initiate treatment with venetoclax.

INTRODUCTION: Following resection of pancreatic acinar cell carcinoma (PACC) distant recurrence remains high. We utilized the national cancer database (NCDB) to evaluate the role of systemic therapy in early-stage resected PACC. METHODS: We queried the NCDB registry from 2004 to 2015 for patients with pathologic stage I-IIB PACC. For each stage, patients who underwent surgery alone (SA) were compared to patients who received systemic and/or radiation therapy in addition to surgery (surgery + therapy [S + T]). RESULTS: A total of 271 patients (101 pI, 81 pIIA, and 89 pIIB) were analyzed. Of all clinically node positive patients (n = 41), the majority (n = 32, 78%) had node-positive disease at resection (pIIB). SA was performed in 112 patients (41.3%), whereas 159 (58.7%) patients received S + T. There was no difference in overall survival (OS) between S + T and SA with respect to pI or pIIA disease. In pIIB disease, S + T was associated with improved OS compared to SA (34.9 vs. 16.9 months, p = 0.031). Single-agent chemotherapy was associated with improved OS for pIIB disease when compared to SA (hazard ratio: 0.38, 95% confidence interval: 0.16, 0.83). CONCLUSION: In resectable PACC, the survival benefit of adjuvant therapy is limited to pathologic stage IIB disease. This benefit is evident even in patients treated with single-agent chemotherapy.

Background Several immune checkpoint inhibitors (ICIs) are approved for the treatment of advanced urothelial carcinoma (UC). There are limited biomarkers for ICI-treated patients with UC. We investigated the association between body composition and clinical outcomes in ICI-treated UC patients. Materials and Methods We conducted a retrospective analysis of 70 ICI-treated patients with advanced UC at Winship Cancer Institute from 2015 to 2020. Baseline computed tomography images within 2 months of ICI initiation were collected at mid-L3 and muscle and fat compartments (subcutaneous, intermuscular, and visceral) were segmented using SliceOMatic v5.0 (TomoVision, Magog, Canada). A prognostic body composition risk score (high: 0–1, intermediate: 2–3, or low-risk: 4) was created based on the β coefficient from the multivariate Cox model (MVA) following best-subset variable selection. Our body composition risk score was skeletal muscle index (SMI) + 2 × attenuated skeletal muscle (SM) mean + visceral fat index (VFI). Concordance statistics (C-statistics) were used to quantify the discriminatory magnitude of the predictive model. Results Most patients (70%) were men and the majority received ICIs in the second- (46%) or third-line (21%) setting. High-risk patients had significantly shorter overall survival (OS; hazard ratio [HR], 6.72; p Conclusion Body composition variables such as SMI, SM mean, and VFI may be prognostic and predictive of clinical outcomes in ICI-treated patients with UC. Larger, prospective studies are warranted to validate this hypothesis-generating data. Implications for Practice This study developed a prognostic body composition risk scoring system using radiographic biomarkers for patients with bladder cancer treated with immunotherapy. The study found that the high-risk patients had significantly worse clinical outcomes. Notably, the study's model was better at predicting outcomes than body mass index. Importantly, these results suggest that radiographic measures of body composition should be considered for inclusion in updated prognostic models for patients with urothelial carcinoma treated with immunotherapy. These findings are useful for practicing oncologists in the academic or community setting, particularly given that baseline imaging is routine for patients starting on treatment with immunotherapy.

The EMPIRE-1 (Emory Molecular Prostate Imaging for Radiotherapy Enhancement-1) trial reported a survival advantage in recurrent prostate cancer salvage radiotherapy (SRT) guided by

INTRODUCTION: While most patients with mantle cell lymphoma (MCL) receive therapy shortly after diagnosis, a subset of patients with indolent-behaving disease can safely defer treatment. In this subgroup, we evaluated the importance of treatment intensity in patients with MCL who defer initial therapy. METHODS: Out of 1134 patients with MCL from 12 academic centers, we analyzed 219 patients who initiated therapy at least 90 days after diagnosis. Patients who received induction with high-dose cytarabine and/or autologous stem cell transplantation (ASCT) in first remission were considered to have received intensive therapy (n = 88) while all other approaches were non-intensive (n = 131). RESULTS: There was no difference in progression-free (PFS; P = .224) or overall survival (OS; P = .167) in deferred patients who received non-intensive vs. intensive therapy. Additionally, univariate and multivariate Cox proportional hazards models were performed for PFS and OS. Treatment at an academic center (HR 0.43, P = .015) was associated with improved OS in both univariate and multivariate models, while intensity of treatment was not associated with improved OS in either model. CONCLUSIONS: These results indicate that intensified initial treatment is not associated with improved survival after deferring initial therapy, although prospective studies are needed to determine which of these patients with MCL may benefit from intensive therapy.

Summary Background Molecular imaging is increasingly used to guide treatment decisions and planning in prostate cancer. We aimed to evaluate the role of 18F-fluciclovine-PET/CT in improving cancer control compared with conventional imaging (bone scan and either CT or MRI) alone for salvage postprostatectomy radiotherapy. Methods In EMPIRE-1, a single-centre, open-label, phase 2/3 randomised controlled trial, patients with prostate cancer with detectable PSA after prostatectomy and negative conventional imaging (no extrapelvic or bone findings) were randomly assigned in a 1:1 ratio to radiotherapy directed by conventional imaging alone or to conventional imaging plus 18F-fluciclovine-PET/CT. Computer-generated randomisation was stratified by PSA concentration, adverse pathology indicators, and androgen deprivation therapy intent. In the 18F-fluciclovine-PET/CT group, radiotherapy decisions were rigidly determined by PET findings, which were also used for target delineation. The primary endpoint was 3 year event-free survival, with events defined as biochemical or clinical recurrence or progression, or initiation of systemic therapy, using univariate and multivariable analyses in patients who received radiotherapy. This trial is registered with ClinicalTrials.gov , NCT01666808 and is closed to new participants. Findings From Sept 18, 2012, to March 4, 2019, 165 patients were randomly assigned, with median follow-up of 3·52 years (95% CI 2·98–3·95). PET findings resulted in four patients in the 18F-fluciclovine-PET/CT group having radiotherapy aborted; these patients were excluded from survival analyses. Median survival was not reached (95% CI 35·2–not reached; 33% of 81 patients had events) in the conventional imaging group compared with not reached (95% CI not reached–not reached; 20% of 76 patients) in the 18F-fluciclovine-PET/CT group, and 3 year event-free survival was 63·0% (95% CI 49·2–74·0) in the conventional imaging group versus 75·5% (95% CI 62·5–84·6) for 18F-fluciclovine-PET/CT (difference 12·5; 95% CI 4·3–20·8; p=0·0028). In adjusted analyses, study group (hazard ratio 2·04 [95% CI 1·06–3·93], p=0·0327) was significantly associated with event-free survival. Toxicity was similar in both study groups, with the most common adverse events being late urinary frequency or urgency (37 [46%] of 81 patients in the conventional imaging group and 31 [41%] of 76 in the PET group), and acute diarrhoea (11 [14%] in the conventional imaging group and 16 [21%] in the PET group). Interpretation Inclusion of 18F-fluciclovine-PET into postprostatectomy radiotherapy decision making and planning significantly improved survival free from biochemical recurrence or persistence. Integration of novel PET radiotracers into radiotherapy decisions and planning for prostate cancer patients warrants further study. Funding National Institutes of Health/National Cancer Institute, Blue Earth Diagnostics, and Winship Cancer Institute of Emory University.

Background Immune checkpoint inhibitor (ICI) therapy is highly effective in metastatic mismatch repair-deficient (MMR-D) colorectal cancer (CRC). In this study, we evaluated molecular and clinical predictors of ICI response in MMR-D CRC. Materials and Methods Patient databases at four cancer institutions were queried. The Fisher exact test was performed to test the association of clinical and molecular markers. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and compared by the log-rank test. Twelve- and 24-month PFS rates were compared by the Z test. Results A total of 60 patients with CRC with MMR-D/microsatellite instability-high who previously received ICIs were identified. Patients with liver metastasis had a lower overall response rate as compared with other sites of metastasis (36.4% vs. 68.7%; p = .081). Patients with MLH1/PMS2 loss had worse 1-year and 2-year PFS rates compared with patients with MSH2/MSH6 loss (84.2% vs. 57.8% and 78.2% vs. 54.2%, respectively; p < .001). There were improved 1-year and 2-year PFS rates in patients with wild-type BRAF when compared with patients with BRAF V600E mutation (73.3% vs. 40%, and 73.3% vs. 26.7%; respectively; p < .001). Patients aged >65 had significantly worse PFS rates as compared with patients aged ≤65 (p < .001). Conclusion BRAF V600E mutation, MLH1 and/or PMS2 loss, as well as age >65 years and liver metastasis, may be predictive of duration of ICI response in patients with MMR-D CRC. Larger cohorts are needed to confirm our findings. Implications for Practice The results of this study reveal clinically important biomarkers that potentially predict immune checkpoint inhibitor response in patients with mismatch repair-deficient colorectal cancer.

BACKGROUND Proton therapy (PRT) is increasingly utilized for pediatric brain tumors to reduce radiation associated treatment effects, but there is a lack of data evaluating PRT in pediatric high-grade glioma (pHGG). The purpose of this analysis is to report patterns of care and clinical outcomes for pHGG patients treated with PRT and enrolled in the prospective Pediatric Proton/Photon Consortium Registry (PPCR). METHODS Fifty-five pHGG participants treated with PRT were enrolled in the PPCR between Jan 2013 and Aug 2020. Progression free (PFS) and overall survival (OS) rates were calculated according to the Kaplan-Meier method. Univariate analyses were performed using Cox proportional hazards model with Firth’s penalization. RESULTS Among 49 patients with complete data, the median age was 12, the majority of patients were male (29), white (35), and non-Hispanic/Latino (41). Histology was grade IV (37), grade III (10) or HGG not specified (8). Resection was gross-total (24), near-total (4), or sub-total/biopsy (17). Six patients received prior RT. The median RT dose was 57.6 Gy (RBE) starting a median of 33.5 days after surgery. 39 patients received chemotherapy. The most common acute treatment toxicities were alopecia (36), fatigue (34), radiation dermatitis (22), nausea/vomiting (19), and headache (19). Median follow-up was 3.14 years (95% CI 1.62-3.97). At 3 years, PFS (95% CI) was 35.5% (20.8-50.6%) and OS was 55.6% (38-70%). Median PFS and OS are 1.6 (1.2-3.1) and 3.6 (1.6-NA) years, respectively. Higher radiation dose was associated with greater PFS (HR 0.97 (0.94-1.01), p=0.059) and OS (HR 0.95 (0.93-0.99), p=0.006). Patients ≤ 3 years at diagnosis (n=8) had 3-year PFS/OS of 72.9%/87.5% vs. 27.8%/49.4% for older patients (p=0.068/0.089, respectively). CONCLUSION These are the first published data with PRT for pHGG. Clinical outcomes are comparable to historical data with photon therapy. Additional analysis of treatment associated toxicity and patient quality-of-life are warranted.

The aim of this study was to characterize the safety of programmed death 1 inhibitors in patients with preexisting autoimmune disease.A medical records review study was conducted on adults with solid tumor malignancies who received ≥1 dose of pembrolizumab or nivolumab at Emory Healthcare from September 4, 2014 until December 31, 2019. All autoimmune patients were included (n = 77), whereas the nonautoimmune patients were randomized and the first 156 patients were included in a 2:1 ratio to autoimmune patients. The primary objective was the comparison of incidence of immune-related adverse events (irAEs) between patients with preexisting autoimmune disease and those without. Secondary objectives included irAE characterization, irAE treatment, and survival analyses.Preexisting autoimmune disease was controlled in all of the autoimmune patients before immunotherapy initiation. The rate of irAE was 32.7% in the nonautoimmune group and 42.9% in the autoimmune group (odds ratio, 0.65; 95% confidence interval, 0.37-1.14; p = 0.130). In the patient population diagnosed with a rheumatologic autoimmune disease, 23.81% of irAEs were considered to be a flare of their preexisting autoimmune disease. Less patients in the autoimmune group experienced a grade ≥3 irAE (21.21% vs 37.25%, p = 0.379) and received systemic corticosteroids (54.55% vs 67.35%, p = 0.241) for the treatment of the irAE.These results suggest that pembrolizumab and nivolumab can be safely administered in patients with controlled preexisting autoimmune diseases without a significant increase in irAE compared with patients without autoimmune diseases. Inclusion of patients with preexisting autoimmune diseases in prospective clinical trials is warranted.

This study evaluated the impact of 18F-fluciclovine positron emission tomography/computed tomography (PET/CT) on salvage radiotherapy management decisions in patients with recurrent prostate cancer (PCa) post-prostatectomy. Methods: Patients with detectable prostate-specific antigen (PSA) post-prostatectomy were randomized to undergo either conventional imaging (CI) only (Arm A) or CI plus 18F-fluciclovine PET/CT (Arm B) prior to radiotherapy. In Arm B, positivity rates on CI and 18F-fluciclovine PET/CT for detection of recurrent PCa were determined. Final radiotherapy decisions, a) to offer radiotherapy or not and b) extent of radiotherapy field - prostate bed only or to include pelvis, were based on 18F-fluciclovine PET/CT findings. Radiotherapy decisions before and after 18F-fluciclovine PET/CT were compared. Statistical significance of decision changes was determined using Clopper-Pearson (exact) binomial method. Prognostic factors were compared between patients with and without decision changes. Results: All 165 patients enrolled in the study had standard-of-care CI and were initially planned for radiotherapy. Sixty-three of 79 (79.7%) patients (median PSA 0.33 ng/mL) who underwent 18F-fluciclovine PET/CT (Arm B) had positive findings. 18F-Fluciclovine PET/CT had significantly higher positivity rate than CI for whole body (79.7% vs 13.9%; P

Background To the authors' knowledge, race-based differences in efficacy for the treatment of patients with advanced non-small cell lung cancer (NSCLC) have not been studied to date due to the underrepresentation of patients of minority backgrounds in pivotal trials. In the current study, the authors examined real-world differences in outcome in a diverse patient population. Methods The authors retrospectively analyzed the clinical outcomes of patients with advanced NSCLC who were treated with single-agent immune checkpoint blockade (ICB) between 2013 and July 2018 at Winship Cancer Institute of Emory University in Atlanta, Georgia. Primary efficacy comparison between Black patients and White patients was performed using bivariate and multivariate analyses for overall survival (OS) and progression-free survival (PFS). Results Data from 257 patients were analyzed. The median age of the patients was 69 years; 50.6% of the patients were female, 63.4% were White, 29.5% were Black, and 7.1% of the patients were of "other" race. ICB was the first-line treatment in 51 patients (19.9%), the second-line treatment in 161 patients (62.6%), and the third-line treatment in 33 patients (12.9%). The most commonly used agents were nivolumab (49.0%), pembrolizumab (25.2%), and atezolizumab (21.3%). No differences with regard to OS (P = .839) and PFS (P = .235) were noted between Black and White patients. The sample overall response rate was 20.6% (15.2% in Black patients and 23.1% in White patients). No differences with regard to OS (P = .081) and PFS (P = .176) were observed between female and male patients. The rate of immune-related adverse events was found to be similar in Black and White patients (20.0% vs 29.9%; P = .148). On multivariate analysis, race was not found to be significantly associated with OS or PFS. Conclusions Real-world analysis of the authors' institutional experience demonstrated similar efficacy and tolerability of ICB in Black versus White patients with advanced NSCLC. Larger multi-institutional studies including other US minority populations would make the findings of the current study more generalizable.

Sézary syndrome (SS) is an aggressive cutaneous T-cell lymphoma with poor survival. We performed a retrospective review of SS patients at Emory University from 1990 to 2020. We collected data on race, clinical characteristics, therapy, and social determinants of health. Clinical endpoints were overall survival (OS) and time to next treatment (TTNT). Univariate association and multivariable analyses were assessed by Cox proportional hazards models. Among 62 patients, 45.2% were AA. The median OS and TTNT were 3.1 years and 6.3 months, respectively, with no difference by race. AA patients had a higher median baseline LDH (360ivs./i232,ip/i = 0.002) and a longer delay in initiation of systemic therapy compared to CC patients (3.17ivs./i2.14 months,ip/i = 0.039), but a shorter commute (lt;10 miles) and no difference in insurance coverage (ip/i = 0.260). AA patients at an academic center had unique clinical features and treatment patterns, but similar survival to CC SS patients.

11 Background: Penile squamous cell carcinoma (pSCC) is a rare neoplasm with a poor prognosis and a need for biomarkers to guide treatment selection. We report an association of baseline inflammatory markers with outcomes in pSCC treated with immune checkpoint inhibitors (ICI). Methods: We performed a retrospective review of patients with pSCC from 2012-2022 at the Winship Cancer Institute at Emory University. Demographics, disease characteristics, and optimal cutoffs of biomarkers prior to ICI initiation were described. Neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), platelet-to-lymphocyte (PLR), and neutrophil-to-eosinophil ratios (NER) were obtained from complete blood count data. Clinical benefit with ICI was defined as complete response, partial response, or stable disease based on RECIST 1.1 criteria. Overall survival (OS) and progression-free survival (PFS) were assessed by the Kaplan-Meier method and univariate Cox regression (UVA) using SAS software with significance level set at p

473 Background: Treatment strategies in resectable gastric cancer (GC) patients include perioperative chemotherapy (PEC), postoperative chemoradiation therapy (POCR), and postoperative chemotherapy (POC). Treatment delay can lead to metastases with unfavorable outcomes. We aim to identify the distribution of patients upstaged to pathologically node positive disease (pLN+) stratified by time and the optimal treatment in this cohort. Methods: We analyzed resected GC patients in the National Cancer Database (2004-2016) with clinically node negative disease (cLN-). Time from diagnosis to first definitive therapy was stratified as ≤2, >2 to ≤4, and >4 weeks. The distribution of patients upstaged from cLN- to pLN+ disease, the concordance between cLN- and pathologically lymph node negative (pLN-) disease based on treatment strategy, and time to first definitive therapy was analyzed. POC and POCR were compared to evaluate their effect on overall survival (OS) in patients with cLN- upstaged to pLN+ disease. Kaplan-Meier test, log-rank test, multivariable Cox proportional hazards analysis (MVA) were performed. Results: Of the 4,828 gastric cancer patients with cLN- disease, 514 (10.65%) patients received PEC and 4,314 (89.35%) patients received upfront surgery followed by POCR/POC. Distribution of patients stratified by time between diagnosis to first definitive treatment - chemotherapy (PEC) or surgery (POC/POCR), for ≤2 weeks was 9.5% vs. 33%, >2 - ≤4 weeks was 28.4% vs. 24.2% and >4weeks was 62% vs 42.7%, respectively. Patients upstaged from cLN- to pLN+ disease in the PEC group was 43.37%(n=206), and 70%(n=2574) in the upfront surgery group (POC/POCR). Of the 206 (43.37%) patients upstaged from cLN- to pLN+ in the PEC cohort, the upstage rate was 7.77% when chemotherapy was started within 2 weeks of diagnosis, compared to 27.67% with >2 to ≤4 weeks, and 64.56% with >4 weeks. Of the 2,574 (70%) patients upstaged in the upfront surgery cohort (POCR/POC), 30.61% were upstaged in ≤2 weeks, 24.95% in >2 to ≤4 weeks, and 44.44% in ≥4 weeks. On MVA, patients with cLN- disease that were pLN- (POCR=766, POC=341) had no significant difference in OS when treated with POCR (HR 1.11, p=0.39) compared to POC. Patients with pLN+ (POCR=2300, POC=907) disease had an association with improved OS when treated with POCR (HR 0.78, p

Although an expanding array of effective treatments has resulted in recent improvement in survival of patients with mantle cell lymphoma (MCL), outcomes remain heterogeneous, and identification of prognostic factors remains a priority. We assessed the prognostic impact of time to progression of disease (POD) after first-line therapy among 455 patients with relapsed MCL. Patients were categorized by duration of first remission as PRF/POD6, defined as progressive disease during induction or POD within 6 months of diagnosis (n = 65; 14%); POD6-24, defined as POD between 6 and 24 months after diagnosis (n = 153; 34%); and POD>24, defined as POD >24 months after diagnosis (n = 237; 53%). The median overall survival from POD (OS2) was 1.3 years (95% confidence interval [CI], 0.9-2.4) for patients with PRF/POD6, 3 years (95% CI, 2-6.8) for those with POD6-24, and 8 years (95% CI, 6.2-NR) for those with POD>24. Median OS2 was inferior in patients with early POD (defined as PRF/POD6 or POD6-24) after both intensive and less intensive frontline treatment. The prognostic performance of time until POD was replicated in an independent cohort of 245 patients with relapsed MCL, with median OS2 of 0.3 years (95% CI, 0.1-0.5) for PRF/POD6, 0.8 years (95% CI, 0.6-0.9) for POD6-24, and 2.4 years (95% CI 2.1-2.7) for POD>24. Early POD is associated with inferior OS2 in patients with relapsed MCL, identifying a high-risk population for future prospective studies.

ImportanceMycosis fungoides and Sézary syndrome (MF/SS) has an increased incidence in Black patients, but clinical characteristics, treatments, and outcomes have been poorly characterized.ObjectiveTo assess racial differences in presentation and outcome and identify drivers for racial disparities in MF/SS.Design, Setting, and ParticipantsA retrospective cohort analysis was conducted of 566 patients with MF/SS diagnosed from 1990 to 2020 and seen at the Winship Cancer Institute of Emory University and Grady Memorial Hospital, both in Atlanta, Georgia. Self-reported race and ethnicity were obtained from patient medical records and analyzed as 2 groups: non-Hispanic Black (Black) and all other races and ethnicities, including Asian, Hispanic, White, and unknown/undeclared (non-Black).Main Outcomes and MeasuresUnivariate and multivariable models and Kaplan-Meier assessments were analyzed for overall survival and time to next treatment. The primary outcome was to assess differences in overall survival by racial and ethnic group. The hypotheses were formulated prior to data collection.ResultsOf the 566 patients with MF/SS identified (mean [SD] age 55 [16.4] years; 270 (47.7%) female), 257 were Black and 309 were non-Black. Black race was associated with increased rates of progression to a higher TNMB stage (39.8% in Black patients vs 29.1% in non-Black patients; P P = .04), but not in patients older than 60 years (HR, 1.20; 95% CI, 0.80-1.81; P = .37). On multivariate analysis, among the cohort without HMF who were younger than 60 years, Black race remained statistically significant when controlling for cancer stage and large-cell transformation (HR, 1.27; 95% CI, 1.08-2.87; P = .43).Conclusions and RelevanceIn this cohort study, Black patients with MF/SS showed distinct clinical presentations and patterns of progression with heterogeneous outcomes depending on age at presentation and presence of HMF.