Prognostic Significance of Angiogenesis and Ki-67, p53, and p21 Expression: A Population-Based Endometrial Carcinoma Study

PURPOSE: For endometrial carcinoma patients, there is a need for improved identification of high-risk groups that may benefit from postoperative adjuvant therapy. We therefore studied the prognostic impact of markers for cell proliferation, cell-cycle regulation, and angiogenesis among endometrial carcinoma patients in a population-based setting. PATIENTS AND METHODS: All patients diagnosed with endometrial carcinoma between 1981 and 1985 in Hordaland County, Norway, were studied. The median follow-up for the survivors was 11.5 years (range, 8 to 15 years), with no patient lost because of insufficient follow-up information. Paraffin-embedded tumor tissue, available in 96% of the cases (n = 142), was studied immunohistochemically for microvessel density (MVD) and expression of Ki-67, p53, and p21 proteins. We used the hot spot method for calculation of MVD, and expression of Ki-67 and p21 protein, because this approach may increase the probability of detecting small aggressive clones of possible prognostic relevance. The importance of these tumor markers was investigated in univariate survival analyses and Cox regression analysis. RESULTS: The majority of traditional clinicopathologic variables was significantly associated with the tumor biomarkers. Age, International Federation of Gynecology and Obstetrics (FIGO) stage, histologic type, histologic grade, MVD, as well as Ki-67, p53, and p21 protein expression, all significantly influenced survival in univariate analyses (P ≤ .05). In the Cox regression analysis, age, FIGO stage, MVD, Ki-67 expression, and p53 expression were the only variables with independent prognostic impact (P ≤ .05), whereas histologic type, histologic grade, and p21 expression had no independent influence. A group of high-risk patients with more than one unfavorable marker was identified. CONCLUSION: In addition to age and FIGO stage, MVD, Ki-67, and p53 protein expression showed an independent prognostic impact. Thus, information derived from routine histologic specimens identified a subgroup of high-risk endometrial carcinoma patients in this population-based study.

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Does Hospitalization Predict the Disease Course in Ulcerative Colitis? Prevalence and Predictors of Hospitalization and Re- Hospitalization in Ulcerative Colitis in a Population-based Inception Cohort (2000-2012)

Journal of Gastrointestinal and Liver Diseases ◽

10.15403/jgld.2014.1121.243.pag ◽

2015 ◽

Vol 24 (3) ◽

pp. 287-292 ◽

Cited By ~ 5

Author(s):

Petra A. Golovics ◽

Laszlo Lakatos ◽

Michael D. Mandel ◽

Barbara D. Lovasz ◽

Zsuzsanna Vegh ◽

...

Keyword(s):

Ulcerative Colitis ◽

Cox Regression ◽

Diagnostic Procedures ◽

Population Based ◽

Disease Course ◽

Inception Cohort ◽

Disease Extent ◽

Cox Regression Analysis ◽

Hospitalization Rates

Background & Aims: Limited data are available on the hospitalization rates in population-based studies. Since this is a very important outcome measure, the aim of this study was to analyze prospectively if early hospitalization is associated with the later disease course as well as to determine the prevalence and predictors of hospitalization and re-hospitalization in the population-based ulcerative colitis (UC) inception cohort in the Veszprem province database between 2000 and 2012. Methods: Data of 347 incident UC patients diagnosed between January 1, 2000 and December 31, 2010 were analyzed (M/F: 200/147, median age at diagnosis: 36, IQR: 26-50 years, follow-up duration: 7, IQR 4-10 years). Both in- and outpatient records were collected and comprehensively reviewed. Results: Probabilities of first UC-related hospitalization were 28.6%, 53.7% and 66.2% and of first re-hospitalization were 23.7%, 55.8% and 74.6% after 1-, 5- and 10- years of follow-up, respectively. Main UC-related causes for first hospitalization were diagnostic procedures (26.7%), disease activity (22.4%) or UC-related surgery (4.8%), but a significant percentage was unrelated to IBD (44.8%). In Kaplan-Meier and Cox-regression analysis disease extent at diagnosis (HR extensive: 1.79, p=0.02) or at last follow-up (HR: 1.56, p=0.001), need for steroids (HR: 1.98, p<0.001), azathioprine (HR: 1.55, p=0.038) and anti-TNF (HR: 2.28, p<0.001) were associated with the risk of UC-related hospitalization. Early hospitalization was not associated with a specific disease phenotype or outcome; however, 46.2% of all colectomies were performed in the year of diagnosis. Conclusion: Hospitalization and re-hospitalization rates were relatively high in this population-based UC cohort. Early hospitalization was not predictive for the later disease course.

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Role of Disease Modifying Treatment in the Risk of Alloimmunization in Transfused Patients with Myelodysplastic Syndromes: A Population-Based Study

Blood ◽

10.1182/blood-2019-123357 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4253-4253

Author(s):

Hanne Rozema ◽

Robby Kibbelaar ◽

Nic Veeger ◽

Mels Hoogendoorn ◽

Eric van Roon

Keyword(s):

Risk Factors ◽

Regression Analysis ◽

Cox Regression ◽

Population Based ◽

Incidence Rates ◽

Blood Products ◽

Cox Regression Analysis ◽

In The Beginning ◽

Observation Period

The majority of patients with myelodysplastic syndromes (MDS) require regular red blood cell (RBC) transfusions. Alloimmunization (AI) against blood products is an adverse event, causing time-consuming RBC compatibility testing. The reported incidence of AI in MDS patients varies greatly. Even though different studies on AI in MDS patients have been performed, there are still knowledge gaps. Current literature has not yet fully identified the risk factors and dynamics of AI in individual patients, nor has the influence of disease modifying treatment (DMT) been explored. Therefore, we performed this study to evaluate the effect of DMT on AI. An observational, population-based study, using the HemoBase registry, was performed including all newly diagnosed MDS patients between 2005 and 2017 in Friesland, a province of the Netherlands. All available information about treatment and transfusions, including transfusion dates, types, and treatment regimens, was collected from the electronic health records and laboratory systems. Follow-up occurred through March 2019. For our patient cohort, blood products were matched for AB0 and RhD, and transfused per the 'type and screen' policy (i.e. electronic matching of blood group phenotype between patient and donor). After a positive antibody screening, antibody identification and Rh/K phenotyping was performed and subsequent blood products were (cross)matched accordingly. The observation period was counted from first transfusion until last transfusion or first AI event. Univariate analyses and cumulative frequency distributions were performed to study possible risk factors and dynamics of AI. DMT was defined as hypomethylating agents, lenalidomide, chemotherapy and monoclonal antibodies. The effect of DMT as a temporary risk period on the risk of AI was estimated with incidence rates, relative risks (RR) and hazard ratios (HR) using a cox regression analysis. Follow-up was limited to 24 months for the cox regression analysis to avoid possible bias by survival differences. Statistical analyses were performed using IBM SPSS 24 and SAS 9.4. Out of 292 MDS patients, 236 patients received transfusions and were included in this study, covering 463 years of follow-up. AI occurred in 24 patients (10%). AI occurred mostly in the beginning of the observation period: Eighteen patients (75%) were alloimmunized after receiving 20 units of RBCs, whereas 22 patients (92%) showed AI after 45 units of RBCs (Figure 1). We found no significant risk factors for AI in MDS patients at baseline. DMT was given to 67 patients (28%) during the observation period. Patients on DMT received more RBC transfusions than patients that did not receive DMT (median of 33 (range: 3-154) and 11 (range: 0-322) RBC units respectively, p<0,001). Four AI events (6%) occurred in patients on DMT and 20 AI events (12%) occurred in patients not on DMT. Cox regression analysis of the first 24 months of follow-up showed an HR of 0.30 (95% CI: 0.07-1.31; p=0.11). The incidence rates per 100 person-years were 3.19 and 5.92 respectively. The corresponding RR was 0.54 (95% CI: 0.16-1.48; p=0.26). Based on our results, we conclude that the incidence of AI in an unselected, real world MDS population receiving RBC transfusions is 10% and predominantly occurred in the beginning of follow-up. Risk factors for AI at baseline could not be identified. Our data showed that patients on DMT received significantly more RBC transfusions but were less susceptible to AI. Therefore, extensive matching of blood products may not be necessary for patients on DMT. Larger studies are needed to confirm the protective effect of DMT on AI. Disclosures Rozema: Celgene: Other: Financial support for visiting MDS Foundation conference.

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Five-Year Outcomes of Stereotactic Body Radiation Therapy (SBRT) for Prostate Cancer-The Largest Experience in China

10.21203/rs.3.rs-190455/v1 ◽

2021 ◽

Author(s):

Xianzhi Zhao ◽

Yusheng Ye ◽

Haiyan Yu ◽

Lingong Jiang ◽

Chao Cheng ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Cox Regression ◽

Progression Free Survival ◽

Cox Regression Analysis ◽

Gu Toxicity ◽

Biochemical Progression ◽

Grade 3 ◽

Very High

Abstract Objective To evaluate the efficacy and toxicity of SBRT for localized prostate cancer (PCa). Moreover, it is the largest-to-date pilot study to report 5-year outcomes of SBRT for localized PCa from China. Methods In this retrospective study, 133 PCa patients in our center were treated by SBRT with CyberKnife (Accuray) from October 2012 to July 2019. Follow-up was performed every 3 months for evaluations of efficacy and toxicity. Biochemical progression-free survival (bPFS) and toxicities were assessed using the Phoenix definition and the Common Terminology Criteria for Adverse Events (CTCAE) v.5.0 respectively. Factors predictive of bPFS were identified with COX regression analysis. Results 133 patients (10 low-, 21 favorable intermediate-, 31 unfavorable intermediate-, 45 high-, and 26 very high risk cases on the basis of the NCCN risk classification) with a median age of 76 years (range: 54–87 years) received SBRT. The median dose was 36.25Gy (range: 34-37.5Gy) in 5 fractions. Median follow-up time was 57.7 months (3.5–97.2 months). The overall 5-year bPFS rate was 83.6% for all patients. The 5-year bPFS rate of patients with low-, favorable intermediate-, unfavorable intermediate-, high-, and very high risk PCa was 87.5%, 95.2%, 90.5%, 86.3%, and 61.6% respectively. Urinary symptoms were all alleviated after SBRT. All the patients tolerated SBRT with only 1 (0.8%) and 1 (0.8%) patient reporting grade-3 acute and late genitourinary (GU) toxicity, respectively. There were no grade 4 toxicities. Gleason score (P < 0.001, HR = 7.483, 95%CI: 2.686–20.846) was the independent predictor of bPFS rate after multivariate analysis Conclusion SBRT is an efficient and safe treatment modality for localized PCa with high 5-year bPFS rates and acceptable toxicities.

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P246 Long-term prognosis of ulcerative colitis and its temporal changes between 1986 and 2015 in a population-based cohort in the Songpa-Kangdong district of Seoul, Korea

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.375 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S271-S271

Author(s):

J M Cha ◽

S H Park ◽

K H Rhee ◽

S N Hong ◽

Y H Kim ◽

...

Keyword(s):

Ulcerative Colitis ◽

Cox Regression ◽

Cumulative Risk ◽

Population Based ◽

Natural Course ◽

Cox Regression Analysis ◽

Mortality Ratio ◽

Cumulative Risks

Abstract Background No population-based study has evaluated the natural course of ulcerative colitis (UC) over three decades in non-Caucasians. We aimed to assess the long-term natural course of Korean patients with UC in a population-based cohort. Methods This Korean population-based SK-IBD cohort included all patients (N = 1013) newly diagnosed with UC during 1986–2015. Disease outcomes and their predictors were evaluated. Results During the median follow-up of 105 months, the overall use of systemic corticosteroids, thiopurines, and anti-tumour necrosis factor (TNF) agents was 40.8%, 13.9%, and 6.5%, respectively. Over time, the cumulative risk of commencing corticosteroids decreased, whereas that of commencing thiopurines and anti-TNF agents increased. During follow-up, 28.7% of 778 patients with proctitis or left-sided colitis at diagnosis experienced proximal disease extension. A total of 28 patients (2.8%) underwent colectomy, demonstrating cumulative risks of colectomy at 1, 5, 10, 20, and 30 years after diagnosis of 1.0%, 1.9%, 2.2%, 5.1%, and 6.4%, respectively. Multivariate Cox regression analysis revealed that extensive colitis at diagnosis (hazard ratio [HR] 8.249, 95% confidence interval [CI] 2.394–28.430), ever use of corticosteroids (HR 6.437, 95% CI 1.440–28.773), and diagnosis in the anti-TNF era (HR 0.224, 95% CI 0.057–0.886) were independent predictors of colectomy. The standardised mortality ratio in UC patients was 0.725 (95% CI 0.508–1.004). Conclusion Korean UC patients may have a better clinical course than Western patients, as indicated by a lower colectomy rate. The overall colectomy rate has continued to decrease over the past three decades.

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Headache as a risk factor for dementia: A prospective population-based study

Cephalalgia ◽

10.1177/0333102413513181 ◽

2013 ◽

Vol 34 (5) ◽

pp. 327-335 ◽

Cited By ~ 22

Author(s):

Knut Hagen ◽

Eystein Stordal ◽

Mattias Linde ◽

Timothy J Steiner ◽

John-Anker Zwart ◽

...

Keyword(s):

Risk Factor ◽

Cohort Study ◽

Cox Regression ◽

Subsequent Development ◽

Population Based ◽

Health Study ◽

Cox Regression Analysis ◽

Hazard Ratios ◽

Increased Risk

Background Headache has not been established as a risk factor for dementia. The aim of this study was to determine whether any headache was associated with subsequent development of vascular dementia (VaD), Alzheimer’s disease (AD) or other types of dementia. Methods This prospective population-based cohort study used baseline data from the Nord-Trøndelag Health Study (HUNT 2) performed during 1995–1997 and, from the same Norwegian county, a register of cases diagnosed with dementia during 1997–2010. Participants aged ≥20 years who responded to headache questions in HUNT 2 were categorized (headache free; with any headache; with migraine; with nonmigrainous headache). Hazard ratios (HRs) for later inclusion in the dementia register were estimated using Cox regression analysis. Results Of 51,383 participants providing headache data in HUNT 2, 378 appeared in the dementia register during the follow-up period. Compared to those who were headache free, participants with any headache had increased risk of VaD ( n = 63) (multivariate-adjusted HR = 2.3, 95% CI 1.4–3.8, p = 0.002) and of mixed dementia (VaD and AD ( n = 52)) (adjusted HR = 2.0, 95% CI 1.1–3.5, p = 0.018). There was no association between any headache and later development of AD ( n = 180). Conclusion In this prospective population-based cohort study, any headache was a risk factor for development of VaD.

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R-HCVAD/R-MTX-Arac (R-HCVAD) Overcomes Risk Features Associated with Inferior Outcomes In the Treatment of Newly Diagnosed, High-Risk Diffuse Large B-Cell Lymphoma (DLBCL).

Blood ◽

10.1182/blood.v116.21.1782.1782 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1782-1782

Author(s):

Anthony R Mato ◽

Tatyana Feldman ◽

Tania Zielonka ◽

Pritish K. Bhattacharyya ◽

Alexandria Campaiola ◽

...

Keyword(s):

High Risk ◽

B Cell ◽

Cox Regression ◽

B Cell Lymphoma ◽

Primary Study ◽

Newly Diagnosed ◽

Ki 67 ◽

Bulky Disease ◽

Poor Risk

Abstract Abstract 1782 Background: Chemo immunotherapy (R-CHOP) has improved outcomes of both GC (germinal center) and ABC (activated B-cell) subtypes of DLBCL. However outcomes in DLBCL patients treated with R-CHOP with ABC subtype (vs. GC) and/or with poor-risk features (High IPI, high Ki-67) remain inferior. These patients might benefit from more dose-intensive or high-dose therapy approaches. In our practice at The John Theurer Cancer Center, we have employed a risk-adaptive strategy with R-HCVAD to treat patients with DLBCL with aggressive features. Methods: Utilizing Kaplan Meier (KM) survival and Cox regression analyses, we conducted a retrospective cohort study to describe the outcome of patients treated with R-HCVAD in the 1st-line setting with the following high-risk features: high Ki-67 (MIB-1), high IPI, multiple extra-nodal (EN) sites, bulky disease or immunohistochemistry (IHC) staining patterns (GC vs. non GC by Hans’ model). The primary study endpoints were PFS and OS. The proportional hazards assumption was met for this analysis. Results: 45 patients (median age 57, range 34–71 yrs) with newly diagnosed DLBCL treated with R-HCVAD (median 6 cycles, range 1–8) were available for this analysis, representing 1010 total months of follow up at-risk. Baseline characteristics included: stage III-IV (90%), IPI ≥ 3 (52%), median Ki-67 (80%, range 10–100%), median EN sites (2), non-GC subtype (34%), bone marrow (BM) involvement (38%), EBER positive (14%), HIV negative (100%). With 17 months (range 9–64 months) median follow up, median OS and PFS (graph) are not yet reached. 2-yr PFS and OS were 80% (95% CI 61–91%) and 78% (95% CI 61–88%) respectively. In Cox regression analysis, survival outcomes were not adversely affected by: patient age > 60 (HR .8, p=.18), LDH > ULN (HR 2.3, p=.3), non-GC IHC pattern (HR .5, p=.5), BM involvement (HR 1.9, p=.4), Ki-67 ≥ 80% (HR 1.7, p=.6) or EN sites ≥ 2 (HR 4.7, p=.15). Conclusions: This analysis represents the largest reported cohort of DLBCL patients treated with R-HCVAD. These data suggest that R-HCVAD can overcome traditional poor-risk features such as high IPI, high Ki-67 and non-GC IHC pattern. Future work will focus on identifying molecular markers for failure in DLBCL patients treated with dose-intensive regimens. A randomized trial comparing R-HCVAD to R-CHOP in selected high-risk patients is warranted. Disclosures: No relevant conflicts of interest to declare.

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suPAR Cut-offs for Stratification of Low, Medium, and High-risk Acute Medical Patients in the Emergency Department

10.21203/rs.3.rs-542503/v1 ◽

2021 ◽

Author(s):

Santeri Seppälä ◽

Andreas Peter Andersen ◽

Kristiina Nyyssönen ◽

Jesper Eugen-Olsen ◽

Harri Hyppölä

Keyword(s):

High Risk ◽

Predictive Value ◽

Cox Regression ◽

Medical Patients ◽

Urokinase Plasminogen Activator Receptor ◽

Cox Regression Analysis ◽

Protein Levels ◽

Reactive Protein ◽

Roche Diagnostics

Abstract Background: Soluble urokinase plasminogen activator receptor (suPAR) levels have previously been associated with readmission and mortality in acute medical patients in the ED. However, no specific cut-offs for suPAR has been tested in this population. Methods: Prospective observational study of acute medical patients. Follow-up of mortality and readmission was carried out for 30- and 90 days stratified into baseline suPAR < 4, 4-6 and > 6 ng/ml. suPAR levels were measured using suPARnostic® Turbilatex assay on a Cobas c501 (Roche Diagnostics Ltd) analyser. Results: A total of 1747 acute medical patients in the ED were included. Median age was 70 (IQR: 57-79) and 51.4% were men. Cox regression analysis showed that suPAR, independently of age, sex and C-reactive protein levels, predicted 30- and 90-day mortality (both p<0.001). Among patients with suPAR below 4 ng/ml (N=804, 46.0%), 8 (1.0%) died within 90-day follow-up, resulting in a negative predictive value of 99.0% and a sensitivity of 94.6%. Altogether 514 (29.4%) patients had suPAR4-6 ng/ml, of whom 43 (8.4%) died during 90-day follow-up. Among patients with suPAR above 6 ng/ml (N=429, 24.6%), 87 patients (20.3%) died within 90-day follow-up, resulting in a positive predictive value of 20.1% and a specificity of 78.7%. Conclusions: suPAR cut-offs of below 4, between 4-6 and above 6 ng/ml can identify acute medical patients who have low, medium or high risk of 30- and 90-day mortality. The turbidimetric assay provides fast suPAR results that may aid in the decision of discharge or admission of acute medical patients.

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Five-year outcomes of stereotactic body radiation therapy (SBRT) for prostate cancer: the largest experience in China

Journal of Cancer Research and Clinical Oncology ◽

10.1007/s00432-021-03785-2 ◽

2021 ◽

Author(s):

Xianzhi Zhao ◽

Yusheng Ye ◽

Haiyan Yu ◽

Lingong Jiang ◽

Chao Cheng ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Cox Regression ◽

Progression Free Survival ◽

Patient Reporting ◽

Cox Regression Analysis ◽

Gu Toxicity ◽

Grade 3 ◽

Very High

Abstract Objective To evaluate the efficacy and safety of SBRT for localized prostate cancer (PCa) with CyberKnife in China. Moreover, it is the largest-to-date pilot study to report 5-year outcomes of SBRT for localized PCa from China. Methods In this retrospective study, 133 PCa patients in our center were treated by SBRT with CyberKnife (Accuray Inc., Sunnyvale, USA) from October 2012 to July 2019. Follow-up was performed every 3 months for efficacy and toxicity evaluation. Biochemical progression-free survival (bPFS) and toxicities were assessed using the Phoenix definition and the Common Terminology Criteria for Adverse Events (CTCAE) v.5.0, respectively. Factors predictive of bPFS were identified with COX regression analysis. Results 133 patients (10 low-, 21 favorable intermediate-, 31 unfavorable intermediate-, 45 high-, and 26 very high risk cases on the basis of NCCN risk classification) with a median age of 76 years (range 54–87 years) received SBRT. The median dose was 36.25 Gy (range 34–37.5 Gy) in 5 fractions. Median follow-up time was 57.7 months (3.5–97.2 months). The overall 5-year bPFS rate was 83.6% for all patients. The 5-year bPFS rate of patients with low-, favorable intermediate-, unfavorable intermediate-, high-, and very high risk PCa was 87.5%, 95.2%, 90.5%, 86.3%, and 61.6%, respectively. Urinary symptoms were all alleviated after SBRT. All patients tolerated SBRT with 1 (0.8%) patient reporting grade-3 acute and 1 (0.8%) patient reporting grade-3 late genitourinary (GU) toxicity, respectively. There were no grade 4 toxicities. Gleason score (P < 0.001, HR = 7.483, 95%CI: 2.686–20.846) was the independent predictor of bPFS rate after multivariate analysis. Conclusion SBRT is an efficient and safe treatment modality for localized PCa with high 5-year bPFS rates and acceptable toxicities.

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Three-year survival outcomes in a prospective cohort evaluating a prognostic 31-gene expression profile (31-GEP) test for cutaneous melanoma (CM).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.9519 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 9519-9519 ◽

Cited By ~ 1

Author(s):

Eddy C. Hsueh ◽

James R. DeBloom ◽

Robert W. Cook ◽

Kelly McMasters

Keyword(s):

High Risk ◽

Cox Regression ◽

Clinical Care ◽

Positive Sentinel Lymph Node ◽

Clinical Registry ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Class 1 ◽

Data Censoring

9519 Background: A 31-GEP test is a validated prognostic tool for predicting the risk of metastasis in CM, classifying patients (pts) as Class 1 (low risk) or Class 2 (high risk). Here we report updated survival analysis from two clinical registry studies (NCT02355574/NCT02355587) designed to prospectively evaluate outcomes in patients for whom the GEP test was part of their clinical care. Methods: Eleven US dermatologic and surgical centers participated using IRB-approved protocols. Participants were CM pts ≥16 years old who had successful 31-GEP test results. Recurrence-free (RFS), distant metastasis-free (DMFS) and overall survival (OS) were assessed using Kaplan-Meier and Cox regression analysis. Results: At data censoring, 340 pts were accrued who had completed at least one follow-up visit. Median age was 58 years (range 18-87), 53.5% were male, median Breslow thickness was 1.2mm (range 0.2-12mm), 18.2% (62/340) were ulcerated, and 11.2% (38/340) had a positive sentinel lymph node (SLN). Median follow-up was 3.2 years for pts without an event. Six percent (16/265) of Class 1 pts had a recurrence compared to 33% (25/75) of Class 2 pts (p < 0.001). Three-year RFS was 96%, 91%, 80%, and 62% for Class 1A, 1B, 2A, and 2B, respectively (p < 0.001). Three-year DMFS was 97%, 93%, 84%, and 80% for Class 1A, 1B, 2A, and 2B, respectively (p < 0.001). Three-year OS was 98%, 90%, 96%, and 74% for Class 1A, 1B, 2A, and 2B, respectively (p < 0.001). Class 2 was an independent predictor of RFS and OS in multivariate analysis (respective HRs: 2.28 and 3.70, p < 0.05). Conclusions: Consistent with results from previous studies, this analysis demonstrates that the GEP test complements conventional staging and improves the ability to identify high-risk CM pts. These results support use of the test for guiding decisions related to follow-up, surveillance, and treatment in CM pts. Clinical trial information: NCT02355574/NCT02355587.

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Interim analysis of survival outcomes in a prospective cohort evaluating a prognostic 31-gene expression profile (GEP) test for melanoma.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.9573 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 9573-9573

Author(s):

Eddy C. Hsueh ◽

James R. DeBloom ◽

Jonathan H. Lee ◽

Jeffrey J. Sussman ◽

Craig L. Slingluff ◽

...

Keyword(s):

High Risk ◽

Interim Analysis ◽

Cox Regression ◽

P Value ◽

Prognostic Information ◽

Clinical Registry ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Class 1

9573 Background: DecisionDx-Melanoma has been validated as an accurate prognosticator of cutaneous melanoma (CM) metastasis risk. The GEP test classifies CM pts as Class 1 (low risk) or Class 2 (high risk). Interim survival analysis from two clinical registry studies (NCT02355574/NCT02355587) designed to prospectively evaluate outcomes in pts for whom the GEP test was performed is described. Methods: Eleven US dermatologic and surgical centers participated in the IRB-approved protocols. Physicians enrolled CM pts who were ≥16 years old and had successful GEP test results. Endpoints of recurrence-free (RFS), distant metastasis-free (DMFS) and melanoma-specific survival (MSS) were assessed using Kaplan-Meier and Cox regression analysis. As an interim analysis at year 3 of an expected 5-year study, the critical alpha level (p-value) was 0.01. Results: At the time of data extraction, 322 pts were accrued and completed at least one follow-up visit. Median age was 58 years (range 18-87), median Breslow thickness (BT) was 1.2mm, 55% were male, 20% (58/296) were ulcerated, and 15% (36/237 biopsied) had a positive sentinel lymph node (SLN). Median follow-up time was 1.5 years for pts without a recurrence. Of 25 recurrent cases, 80% (20/25) were Class 2 and 40% (10/25) were SLN-positive. Two percent of Class 1 pts had a recurrence compared to 6% (12/201 biopsied) of SLN-negative pts. Of the SLN-negative pts who recurred, 75% (9/12) were called Class 2. Combined GEP and SLN risk prediction identified 88% (21/24) of recurrences. Kaplan-Meier event rates for each class are shown in the table. In Cox multivariate analysis, BT and GEP Class 2 were significant predictors of recurrence (p<0.01 for each). Conclusions: Results of this analysis show that the GEP test provides prognostic information that complements conventional staging and significantly enhances identification of high risk CM pts, consistent with reported validation studies.The results support use of the test for guiding surveillance decisions and enrollment of CM pts in clinical trials. Clinical trial information: NCT02355574, NCT02355587. [Table: see text]

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