ALK actionable mutations (muts) within cancer types and their responses to crizotinib (CZ).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14739-e14739
Author(s):  
Lin Li ◽  
Caixia Liu ◽  
Jun Zhao ◽  
Lin Gen ◽  
Xiaorong Dong ◽  
...  
Keyword(s):  
Small Sample Size ◽  
Clinical Information ◽  
Small Sample ◽  
Rank Test ◽  
Unknown Primary ◽  
First Line ◽  
First Line Therapy ◽  
Kaplan Meier ◽  
Variant Information ◽  
Cancer Types

e14739 Background: CZ was recommended by NCCN for ALK-rearranged metastasis NSCLC as first-line therapy. Knowledge on the occurrence of ALK actionable muts within cancer types and the responses of ALK fusion types to CZ could better guide the treatment of ALK-rearranged pts. Methods: 772 ALK-mutated pts (with any ALK muts) detected by tissue/ctDNA NGS in our institution from Oct. 2016 to Oct. 2018 were included. ALK+ (with any ALK actionable muts) and EGFR- (with no EGFR actionable muts) pts treated with CZ at any line were included for survival analysis. Progress-free survival (PFS) was estimated using Kaplan-Meier method and compared using log-rank test. Results: 339 ALK+ pts were analyzed, including 331 lung cancer (LC: 265 NSCLC; 1 SCLC; 65 Unknown histology), 3 brain cancer (BC), 1 colon cancer (CC), 3 cancer of unknown primary (CUP), and 1 with no clinical information. The most common ALK mut was fusion (331/339), including 315 EML4-ALK, 5 KIF5B-ALK, 4 STRN-ALK, 1 ACSL3-ALK, 1 CLIP4-ALK, 1 DCTN1-ALK, 1 HIP1-ALK, 1 SRBD1-ALK, 1 TFG-ALK, and 1 ZFP161-ALK. Fusion position was known for 308 EML4-ALK, including 132 V1, 108 V3, 32 V2, 19 V5’, and 17 other variants (Vx). Except for 2 V1 with CUP, 1 KIF5B-ALK with CUP, 1 Vx with CC, and 1 EML4-ALK (no variant information) with BC, all the other fusions occurred in LC. ALK F1174L was detected only in 2 pts, both of whom had BC, specifically neuroblastoma. CZ was given to 76 ALK+ EGFR- pts (mPFS: 9 mo, 95% CI: 8 – 13), including 70 EML4-ALK and 6 non- EML4-ALK (mPFS: 10 vs. 9 mo, p = 0.7). Though non-significant, V1 (n = 32) on average had a longer mPFS than V3 (n = 28) (12 vs. 8 mo, p = 0.3), which may partially be explained by the younger age at diagnosis of V1 than V3 (48 vs. 53, p = 0.005). 1 TFG-ALK, 1 CLIP4-ALK, 1 DCTN1-ALK, 1 HIPI-ALK, 1 ZFP161-ALK, and 1 KIF5B-ALK achieved a PFS of 3, 4, 8, 9, 13, and 19 mo on CZ, respectively. 1 SCLC (V3) received CZ at first-line progressed after 6 mo. Conclusions: Though majority of the ALK actionable muts were commonly found in LC, some alterations may occur more often in other cancer types, such as F1174L in neuroblastoma. Some fusion types (e.g. TFG-ALK) may benefit less from CZ than others (e.g. KIF5B-ALK). Limited by relative small sample size, these results merit further validation and investigation.

Improved Postoperative Survival for Intraductal- Growth Subtype of Intrahepatic Cholangiocarcinoma

2016 ◽  
Vol 82 (11) ◽  
pp. 1133-1139 ◽  
Author(s):  
Laura L. Dover ◽  
Rojymon Jacob ◽  
Thomas N. Wang ◽  
Joseph H. Richardson ◽  
David T. Redden ◽  
...  
Keyword(s):  
Intrahepatic Cholangiocarcinoma ◽  
Small Sample Size ◽  
Tumor Stage ◽  
Small Sample ◽  
Postoperative Survival ◽  
Rank Test ◽  
Intraductal Growth ◽  
Kaplan Meier ◽  
Disease Free

Intrahepatic cholangiocarcinoma (ICC) is classified according to the following subtypes: mass-forming (MF), periductal infiltrating (PI), and intraductal growth (IG). The aim of this study is to measure the association between ICC subtypes and patient survival after surgical resection. Data were abstracted on all patients treated with definitive resections of ICC at a single institution between 2000 and 2011 with at least three years follow-up. Survival estimates were quantified using Kaplan-Meier curves and compared using the log-rank test. There were 37 patients with ICC treated with definitive partial hepatectomies with a median survival of 33.5 months. Tumor stage (P < 0.0001), satellitosis (P < 0.001), lymphovascular space invasion (P = 0.003), and macroscopic subtype (P = 0.003) were predictive of postoperative survival. Disease-free survivals for MF, PI, and IG subtypes, respectively, were 30 per cent, 0 per cent, and 57 per cent (P = 0.017). Overall survivals among ICC macroscopic subtypes were as follows: MF 37 per cent, PI 0 per cent, and IG 71 per cent (P = 0.003). Although limited by the small sample size of this rare cancer, this study demonstrates significant differences among macroscopic subtypes of ICC in both disease-free survivals and overall survivals after definitive partial hepatectomy.

Gemcitabine (G) + nab-paclitaxel (nab-P) versus G in patients (pts) with advanced pancreatic cancer (PDAC) after FOLFIRINOX: A single center, retrospective review.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 348-348 ◽  
Author(s):  
Edmond Mankee Chan ◽  
Theodore S. Hong ◽  
Jeffrey William Clark ◽  
Lawrence Scott Blaszkowsky ◽  
Jill N Allen ◽  
...  
Keyword(s):  
Cox Regression ◽  
Small Sample Size ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Small Sample ◽  
First Line Therapy ◽  
Kaplan Meier ◽  
Patient Decision ◽  
Line Setting ◽  
Marginal Improvement

348 Background: The MPACT study showed that G + nab-P improved OS and PFS over G as first line therapy for metastatic PDAC. However, there is limited data studying this combination after FOLFIRINOX. Here, we compared G + nab-P to G in pts with advanced PDAC previously treated with FOLFIRINOX. Methods: From 3/2010 to 5/2014, we identified all pts treated with FOLFIRINOX for PDAC who later received G +/- nab-P at the MGH. PFS and OS were calculated from the start of G +/- nab-P and analyzed using Kaplan-Meier and Cox-regression analyses. Results: 40 pts received G + nab-P and 36 pts received G. 29 of 36 pts in the G arm started G prior to the FDA approval of nab-P. Baseline characteristics were similar except 7 pts in the G + nab-P arm had locally advanced PDAC at start of G + nab-P while all other pts in both arms had metastatic PDAC. The median OS was 4.8 months (m) for G + nab-P vs 4.2m with G (HR 0.69, 95% CI 0.42 – 1.13). The median PFS was 2.4m for G + nab-P vs 1.8m for G (HR 0.70, 95% CI 0.44-1.12). The median OS did not change when the analysis was restricted to pts with metastatic PDAC – 4.8m vs 4.2m (HR 0.68, 95% CI 0.41-1.14). The median PFS for pts with metastatic PDAC was also similar – 2.7m for G + nab-P vs 1.8m with G (HR 0.69, 95% CI 0.42-1.12). Pts treated with G + nab-P received a median of 4m of treatment vs 2m for pts with G alone. The median relative dose of G was 50% of the maximum anticipated dose over the first 8 weeks for G + nab-P vs 66% with G. The median relative dose for nab-P was 50% of the maximum anticipated dose over the first 8 weeks. The most common reasons for discontinuing therapy were progression (62.5% vs 69%), patient decision (5% vs 11%), and infection (12.5% vs 0%). Conclusions: Although retrospective and limited by a small sample size, our data suggests that G + nab-P could be considered over G for advanced PDAC after FOLFIRINOX. However, G + nab-P affords marginal improvement in median OS and PFS, thus calling for the need to explore other agents in the second-line setting. Moreover, our experience suggests that the addition of nab-P led to a reduction in the achievable dose of G – raising the question of tolerability in combining further agents to G + nab-P in this setting.

Germline variant in HSD3B1 (1245 A>C) and response to abiraterone acetate plus prednisone (AA) in men with new onset metastatic castration-resistant prostate cancer (mCRPC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 173-173
Author(s):  
Andrew W Hahn ◽  
David Michael Gill ◽  
Roberto Nussensveig ◽  
Austin Poole ◽  
James M. Farnham ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Small Sample Size ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Small Sample ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Adrenal Androgen ◽  
University Of Utah ◽  
First Line Therapy

173 Background: The HSD3B1 gene encodes the enzyme 3β-hydroxysteroid dehydrogenase-1 (3βHSD1), which catalyzes adrenal androgen precursors into dihydrotestosterone, the most potent androgen. Recently, multiple reports validated the role of HSD3B1 (1245 A>C) variant in predicting response to androgen deprivation therapy (ADT) in castration sensitive prostate cancer. The objective of this study was to correlate HSD3B1 variantwith response AA in first-line therapy for men with mCRPC. Methods: Clinical data and samples were from a prospectively maintained prostate cancer registry at the University of Utah. Genotyping was performed as described by Hearn at al (Lancet Oncology, 2016). Primary endpoint was progression-free survival in first-line AA in men with mCRPC. We performed pre-specified multivariate analyses to assess the independent predictive value of HSD3B1 genotype on PFS on AA (Table). Results: 76 men with mCRPC treated with first-line AA were included. In multivariate analysis, HSD3B1 (1245 A>C) did not predict response to first-line AA (Table). Conclusions: This hypothesis-generating data shows that inherited variant alleles in HSD3B1 do not predict response to first-line AA in mCRPC. This finding could be due to the ability of AA metabolites to act as both agonist (3-keto-5α-abiraterone) and antagonist (Δ4-abiraterone) on androgen signaling or our small sample size. [Table: see text]

Serial cell-free DNA (cfDNA) sampling in advanced pancreatic ductal adenocarcinoma (PDAC) patients may predict therapeutic outcome.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 423-423
Author(s):  
Gehan Botrus ◽  
Yu Fu ◽  
Mohamad Bassam Sonbol ◽  
Leylah Drusbosky ◽  
Daniel H. Ahn ◽  
...  
Keyword(s):  
Overall Survival ◽  
Progression Free Survival ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
First Line ◽  
Free Survival ◽  
Probability Of Survival ◽  
First Line Therapy ◽  
Kaplan Meier ◽  
Next Generation Sequencing Ngs

423 Background: Advanced PDAC remains a deadly disease with a 5-year survival rate of less than 10%. cfDNA - based next generation sequencing (NGS) may identify actionable alterations in patients with PDAC. In this study, we aim to determine the feasibility of utilizing serial cfDNA NGS testing and its potential relevance in predicting therapeutics outcomes. Methods: A total of 23 PDAC patients with PDAC cfDNA isolated from plasma collected at diagnosis and upon disease progression to first line SOC therapy and were analyzed on a 73-74 gene NGS panel (Guardant Health). Changes in molecular profiles from baseline to progression were analyzed for overall survival, progression free survival (PFS), and treatment response. PFS and OS were analyzed using the Kaplan-Meier method and the log-rank test was used to compare the survival of different groups of patients. All p-values were two-sided. Analyses were performed using R (version 3.5.1, R Foundation, Vienna, Austria). Results: In this retrospective study, the 1-year probability of survival was 71% (median 473 days) and the 1-year PFS was 14% (median 212 days). TP53 and KRAS were the most frequently mutated genes identified in baseline samples, with 78% prevalence for each. Patients with clearance of TP53 17% (3/18) patients and/or KRAS 33% (6/18) patients clones after first line therapy significantly increases PFS (p=0.0056 and p=0.037, with HR of 0.087 and 0.32, respectively). However, appearance of TP53 or KRAS alterations upon progression does not significantly affect overall survival or PFS. Conclusions: The preliminary results from this study suggest that cfDNA clearance of TP53 and/or KRAS alterations may predict for improved PFS in PDAC. Confirmation of these findings in larger studies is warranted.

191 Association of immune related adverse events with the efficacy of immune checkpoint inhibitors in metastatic renal cell carcinoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A205-A206
Author(s):  
Vasilii Bushunow ◽  
Leonard Appleman ◽  
Roby Thomas
Keyword(s):  
Renal Cell Carcinoma ◽  
Adverse Events ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Kaplan Meier

BackgroundImmune checkpoint inhibitors (ICI) are first-line therapy for tumors including metastatic renal cell carcinoma (mRCC). Use of ICI is complicated by diverse immune-related adverse events (irAEs), which can add significant morbidity but are also associated with improved efficacy of therapy.1 2 Risk factors for development of irAE are still poorly understood. We hypothesized that patients with mRCC treated with ICI as first-line therapy have higher rates of developing irAE’s than patients previously treated with other therapies.MethodsWe conducted a single-institution, retrospective medical record review of patients with mRCC treated with immune-checkpoint inhibitors from March 2011 through April 15, 2020. We identified therapy duration, and presence, severity, and treatment of adverse events. We defined overall survival as time elapsed from date of diagnosis until death or until completion of study. We classified severity of adverse events according to CTCAE guidelines. Statistical methods included univariate Cox proportional hazards and logistic regression models, and Kaplan-Meier curves were plotted for subgroups.ResultsA total of 64 unique charts were reviewed. 18 patients (28%) of patients were treated with ICI as first-line therapy. 28 patients (44%) experienced immune-related adverse events with a total of 40 irAE’s identified. Most irAE were grade I-II (78%), with 7 (17%) grade III and 1 (2.4%) grade IV irAE’s. Most common sites were skin (29%), thyroid (20%) and gastrointestinal (15%). Patients with irAE had increased survival compared to those who did not have irAE (median survival not reached, vs 139 weeks, p=0.0004) (figure 1). This finding remained after excluding patients who had only experienced dermatologic irAE (median survival not reached in non-derm irAE subgroup, vs 144 weeks for dermatologic or no irAE, p=0.01) (figure 2). Patients treated with ICI as first line therapy had greater rates of developing irAE (72%) than those who had prior therapies (32%) (OR 5.4; p = 0.006). There was no association between histology type and rate of irAE.Abstract 191 Figure 1Kaplan-Meier survival plot of OS between patients with any irAE and those without any irAEAbstract 191 Figure 2Kaplan-Meier survival plot of OS between patients with non-dermatologic irAE and those without any irAE or only dermatologic irAEConclusionsThe development of irAE’s in patients with mRCC treated with ICI is associated with longer survival. This study joins the growing body of evidence showing that presence of irAE’s is associated with increased treatment efficacy. Use of ICI as first-line therapy is associated with higher risk of irAE. Given growing use of ICI as first-line therapy, further study to predict onset and severity of irAE’s is required.AcknowledgementsHong Wang, PhD, for statistical support.Ethics ApprovalThis study was approved by the University of Pittsburgh Institutional Review Board. Approval number STUDY19100386.ReferencesElias R, Yan N, Singla N, Levonyack N, Formella J, Christie A, et al. Immune-related adverse events are associated with improved outcomes in ICI-treated renal cell carcinoma patients. J Clin Oncol 2019;37(7):S645.Verzoni E, Cartenì G, Cortesi E, et al. Real-world efficacy and safety of nivolumab in previously-treated metastatic renal cell carcinoma, and association between immune-related adverse events and survival: the Italian expanded access program. J Immunother Cancer 2019;7(1):99.

Trends in glassy cell cervical cancer in the United States from 1973-2015: Analysis based on SEER database.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17502-e17502
Author(s):  
Anahat Kaur ◽  
Shuai Wang ◽  
Tarek N. Elrafei ◽  
Lewis Steinberg ◽  
Abhishek Kumar
Keyword(s):  
United States ◽  
Cervical Cancer ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Small Sample Size ◽  
Black Population ◽  
The United States ◽  
Small Sample ◽  
Cervix Uteri ◽  
Kaplan Meier

e17502 Background: Glassy cell carcinoma of cervix (GCCC) is a rare histological subtype of cervical cancer which has historically been associated with rapidly progressive disease, early development of metastases and overall poor prognosis. We attempt to define real-world trends in GCCC in the United States based on data from SEER (Surveillance, Epidemiology and End Results) database. Methods: We extracted data from the US National Cancer Institute's SEER 2018 dataset using ICD-O code for ‘Cervix Uteri Glassy Cell Carcinoma’. All patients who were diagnosed between 1973-2015 were included. Statistical analysis was done using SPSS 26. Kaplan Meier curve was used for survival analysis. Results: Data for a total of 57 patients with GCCC was available from 1975 to 2017. Median age at diagnosis was 38 years (range 30.5-44.5). Increased frequency of cases was noted in white females (77.2%) as compared to black population (22.2%). Most cases initially presented with localized or regional spread (47.4% and 40.4% respectively) with distant metastasis seen in only 10.5% patients. Data analysis revealed that 63.2% patients had Grade III poorly differentiated carcinoma, 66.7% received radiation therapy, 57.9% underwent chemotherapy and 59.6% had cancer direceted surgery performed. Calculated mean overall survival was 121.9 months. We were unable to calculate 5 year and 10 year median overall survival due to small sample size and censored data. Conclusions: GCCC is a rare histologic type of cervical cancer that presents at a younger age, is more frequently seen in white females and is commonly associated with localized or regional spread at time of initial presentation.[Table: see text]

scholarly journals Adherence Over Time: The Course of Adherence to Customized Diabetic Insoles as Objectively Assessed by a Temperature Sensor

2017 ◽  
Vol 12 (3) ◽  
pp. 695-700 ◽  
Author(s):  
Dominic Ehrmann ◽  
Monika Spengler ◽  
Michael Jahn ◽  
Dea Niebuhr ◽  
Thomas Haak ◽  
...  
Keyword(s):  
Diabetic Foot ◽  
Temperature Sensor ◽  
Small Sample Size ◽  
Temperature Sensors ◽  
Small Sample ◽  
Gender Effects ◽  
Kaplan Meier ◽  
Foot Problems ◽  
Mean Time

Background: Temperature sensors are an objective way to assess adherence to diabetic footwear. Good adherence is essential for the prevention of diabetic foot problems. Little is known about the long-term course of adherence in patients at risk for diabetic foot problems. Method: A temperature sensor was incorporated into the specialized footwear of patients with type 2 diabetes after their first plantar ulceration. Kaplan-Meier curve was used to analyze when patients started to become nonadherent (not wearing the footwear for two straight weeks). Gender effects on adherence were also analyzed. Results: 26 patients with a mean observation time of 133.5 days could be analyzed. Mean wearing time of diabetic footwear was 4.2 ± 3.6 h/day (Mdn = 3.4 h/day; interquartile range = 0.5-7.0 h/day) and on 51% of the days patients did not wear their footwear at all. Kaplan-Meier curve revealed that the mean time of adherence was 27.5 weeks. Men achieved a mean time of adherence of 30.5 weeks, while women only achieved 14 weeks. However, due to the small sample size, this difference was not statistically significant. Conclusions: Temperature sensors revealed a low long-term adherence to diabetic footwear. Women seemed to be at a higher risk for earlier nonadherent behavior. Adherence to diabetic footwear should be closely monitored and tailored intervention strategies should be developed.

Abstract 13215: Gender-affirming Hormones Are Associated With Increased Risk of QT Prolongation in Transgender Females

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Daniel Antwi Amoabeng ◽  
Ahmed Hanfy ◽  
Munadel Awad ◽  
Bryce D Beutler ◽  
Amneet Rai ◽  
...  
Keyword(s):  
Qt Interval ◽  
Small Sample Size ◽  
Qt Prolongation ◽  
Small Sample ◽  
Rank Test ◽  
Qt Interval Prolongation ◽  
Northern Nevada ◽  
Increased Risk ◽  
Before And After ◽  
Signed Rank Test

Introduction: Women have a longer QT interval than men. This sex-specific difference is attributed to hormones associated with the biological female sex. Male-to-female transgender individuals often take antiandrogens such as spironolactone or goserelin in addition to estrogens to suppress testosterone effects while increasing feminine features. Effects of gender-affirming hormone therapy (GHT) on the QT interval in these individuals remains to be elucidated. Hypothesis: We assessed the hypothesis that the use of GHT is associated with an increased risk for QT interval prolongation in transgender females. Methods: We identified 46 transgender females through a search of the electronic medical records of a Veterans Administration hospital in Northern Nevada. Patients with a diagnosis of congenital long QT syndrome were excluded. Of these, 13 patients had ECGs before and after initiation of GHT and were included. We adapted the Tisdale score using the auto-calculated corrected QT interval (QTc) to estimate the risk of QT prolongation. Age, QTc, and Tisdale scores before and after GHT initiation were compared using the Wilcoxon signed-rank test. All tests were performed as two-tailed at a 5% level of significance. Results: All 13 study patients were taking estrogens. Of these, 3 (23.1%) were taking goserelin and 9 (69.2%) were taking spironolactone. Mean ± SEM age at ECG acquisition was 45.0 ± 4.4 and 47.7 ± 4.7 years before and after the initiation of GHT respectively. Mean ± SEM QTc after initiation of GHT was significantly higher compared to the baseline (467.5 ± 12.8 ms vs. 428.2 ± 7.1 ms) (Figure 1A). The average baseline Tisdale score was significantly smaller on follow-up (1-point vs. 3 points) (Figure 1B). Conclusions: GHT appears to be associated with increased QTc in transgender women. This needs to be interpreted with caution owing to the very small sample size in this study. Further studies to investigate the strength of this association, if it exists, are warranted.

Epidoxorubicin versus no treatment as consolidation therapy in advanced ovarian cancer: results from a phase II study

2006 ◽  
Vol 16 (Suppl 1) ◽  
pp. 74-78 ◽  
Author(s):  
G. Bolis ◽  
S. Danese ◽  
S. Tateo ◽  
E. Rabaiotti ◽  
G. D'Agostino ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Advanced Ovarian Cancer ◽  
Figo Stage ◽  
Pathologic Response ◽  
Rank Test ◽  
Complete Pathologic Response ◽  
First Line ◽  
Histologic Diagnosis ◽  
Treatment Groups ◽  
First Line Therapy

To compare the effect of epidoxorubicin given for 4 months versus no treatment in the survival of patients with advanced ovarian cancer and complete pathologic response after first-line surgery and chemotherapy with platinum-based schedules, we conducted a multicenter randomized clinical trial. Patients with histologic diagnosis of epithelial ovarian cancer FIGO stage III or IV at first diagnosis; complete pathologic response at second-look laparotomy/laparoscopy or complete clinic response; and those who have had first-line therapy including surgery and one regimen containing cisplatin or carboplatinum were eligible for the study and were randomly allocated to epidoxorubicin 120 mg/sqm or no treatment. A total of 64 women were allocated to epidoxorubicin and 74 to no treatment. There were 20 and 19 deaths, respectively, in the epidoxorubicin and no-treatment groups. The 3-year percent overall survival was 79.0% and 78.7%, respectively, in the no-treatment and epidoxorubicin groups (log-rank test, P= 0.93).

Treatment Patterns and Clinical Outcomes of Patients with Sézary Syndrome at Emory University

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 22-23
Author(s):  
Dylan J Martini ◽  
Subir Goyal ◽  
Jeffrey M. Switchenko ◽  
Mary Jo Lechowicz ◽  
Pamela B. Allen
Keyword(s):  
Systemic Therapy ◽  
Hdac Inhibitors ◽  
Prognostic Biomarkers ◽  
P Value ◽  
First Line ◽  
First Line Therapy ◽  
Kaplan Meier ◽  
Line Setting ◽  
Systemic Therapies ◽  
White Patients

Introduction Sézary syndrome (SS) is an aggressive, leukemic subtype of cutaneous T-cell lymphoma (CTCL) with a median survival of 3-5 years. Approved therapies include skin-directed therapy, radiation, and systemic therapies such as chemotherapy, histone deacetylase (HDAC) inhibitors, interferon, extracorporeal photopheresis (ECP), and oral retinoids. There is no consensus first-line therapy for SS and there is limited data regarding prognostic biomarkers. We assessed treatment patterns, outcomes, and racial differences at our institution. Methods We performed a retrospective review of 62 patients at Winship Cancer Institute of Emory University from 1990-2020 with a confirmed diagnosis of SS. Clinical data collected from the electronic medical record included demographics, baseline laboratory values, disease characteristics, and therapy. Clinical outcomes were measured by overall survival (OS) and time to next treatment (TTNT). OS was measured from time of diagnosis to date of death or last follow-up. TTNT was defined as the number of months from the start of the first line of therapy until the initiation of the subsequent therapeutic regimen. Descriptive analysis was performed for each variable and a comparison between African American (AA) and white patients was performed using ANOVA for numerical covariates and chi-square test or Fisher's exact test for categorical covariates. Kaplan-Meier curves for OS and TTNT were generated for the whole cohort. A Kaplan-Meier curve was also generated to compare time from diagnosis to initiation of first systemic therapy stratified by race along with the log-rank p-value. The univariate association of baseline variables with OS and TTNT was assessed by Cox proportional hazards models and the multivariable analyses (MVA) were performed on variables that had p-value less than 0.05 on univariate analyses. Results Males made up (58.1%) of our patients and the median age at diagnosis was 65.9 years. Nearly one-half (45.2%) of patients were AA. The median Sézary count at diagnosis was 1320 cells/uL. The median time from diagnosis to first systemic therapy was 2.4 months and the median number of systemic therapies was 3.0. Information regarding systemic treatments received after diagnosis is presented inTable 1. The most common first-line systemic therapies were oral retinoids (43.5%), ECP (32.3%), and interferon (30.6%). HDAC inhibitors and total skin electron beam (TSEB) radiation were common treatments beyond first line (46.8% received HDAC inhibitors, 38.7% received TSEB), but were rarely used in the first-line setting. The median OS and TTNT were 3.1 years and 6.3 months, respectively(Figure 1). In MVA, elevated WBC and LDH were significantly associated with shorter OS (WBC HR: 1.05, 95% CI: 1.01-1.08, p=0.01; LDH HR: 1.003, 95% CI: 1.001-1.005, p=0.011) and shorter TTNT (WBC HR: 1.04, 95% CI: 1.002-1.08, p=0.041; LDH HR: 1.002, 95% CI: 1.001-1.004, p=0.048). In analysis by race, AA patients had a higher proportion of females compared to non-hispanic white patients (53.6% vs 28.1%, p=0.045). AA patients also had lower median hemoglobin at diagnosis (12.6 vs 14.3, p=0.036), higher median LDH at diagnosis (360 vs 232, p=0.002), and longer median time from diagnosis to first systemic therapy compared to non-hispanic white patients (3.17 months vs 2.14 months, p=0.039,Figure 2). Conclusions SS is an aggressive subtype of CTCL with no consensus first-line therapy and limited data on prognostic biomarkers. In our cohort, oral retinoids, ECP, and interferon were the most commonly utilized treatments in the first-line setting. Elevated WBC and LDH were significantly associated with both OS and TTNT which suggests that these may have value as prognostic biomarkers in SS. AA patients may have delayed time from diagnosis to starting systemic therapy and higher LDH at diagnosis. This data is hypothesis-generating and should be validated in larger, prospective studies. Disclosures Allen: Bayer:Consultancy, Other;Imbrium:Consultancy, Other;Research to Practice:Speakers Bureau;Clinical Care Options:Speakers Bureau;Curio Sciences:Honoraria.

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