PROGNOSTIC FACTORS IN PATIENTS WITH APPENDICULAR MYXOFIBROSARCOMA

ABSTRACT Objective: Myxofibrosarcoma (MFS) is a common soft tissue sarcoma (STS) that affects the extremities in elderly patients. The objective was to analyze the prognostic factors and outcomes of patients with MFS treated at a single institution. Methods: We retrospectively reviewed the records of 75 patients with MFS. We compared age, sex, tumor size and location, grade and stage of the disease. Median age was 49.7 years (range, 1 to 88 y). Location: upper extremity (25.4%), lower extremity (66.6%) and pelvis (8%). Patients had high-grade tumors in 46.7% of the reports. Margins were negative in 76% of the cases. Bivariate Cox regression analysis was used to determine associations between clinical and treatment factors with local recurrence (LR). Results: Median follow-up time was 30.7 months (range, 1.8 to 383.8 m). We found 26.7% of LR. Distant metastasis (DM) was reported in 27 (36%) patients. Lung was the most common site of DM, reported in 92.6% of patients. Overall survival (OS) with metastasis was 21.2 months (range, 4.8 to 114.8 m). Predictors of OS were grade, LR (hazard ratio [HR] 5.13, 95% confidence interval, 2.15-12.24, P <0.001), and DM (HR 540.97, 95% confidence interval, 5.04-58112.03, P< 0.001). Conclusions: Tumor grade, LR, positive margins and DM were significant predictors of poor OS prognosis. Level of Evidence IV, Case Series.

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Risk Factors for Failure in Hammertoe Surgery

Foot & Ankle International ◽

10.1177/1071100720904931 ◽

2020 ◽

Vol 41 (5) ◽

pp. 562-571 ◽

Cited By ~ 3

Author(s):

Rachel H. Albright ◽

Moiz Hassan ◽

Jacob Randich ◽

Robert O’Keefe ◽

Erin E. Klein ◽

...

Keyword(s):

Risk Factors ◽

Cox Regression ◽

Elective Surgery ◽

Case Series ◽

Retrospective Case ◽

Level Of Evidence ◽

Cox Regression Analysis ◽

First Ray ◽

Pip Joint

Background: Hammertoe correction is perhaps the most common elective surgery performed in the foot, yet rates of symptomatic recurrence and revision surgery can be high. In this study, we aimed to identify patient and provider risk factors associated with failure after hammertoe surgery. Methods: Consecutive patients with a minimum of 6 months’ follow-up undergoing hammertoe surgery within a single, urban foot and ankle practice between January 1, 2011, and December 31, 2013, served as the basis of this retrospective cohort study. Cox regression analysis was used to identify important predictor variables obtained through chart and radiographic review. One hundred fifty-two patients (311 toes) with a mean age of 60.8 ± 11.2 years and mean follow-up of 29.5 ± 21.2 months were included. Results: Statistically significant predictors of failure were having a larger preoperative transverse plane deviation of the digit (hazard ratio [HR], 1.03 for each degree; P < .001; 95% CI, 1.02, 1.04), operating on the second toe (vs third or fourth) (HR, 2.23; P = .003; 95% CI, 1.31, 3.81), use of a phalangeal osteotomy to reduce the proximal interphalangeal (PIP) joint (HR, 2.77; P = .005; 95% CI, 1.36, 5.64), and using less common/conventional operative techniques to reduce the PIP joint (HR, 2.62; P = .03; 95% CI, 1.09, 6.26). Concomitant performance of first ray surgery reduced hammertoe recurrence by 50% (HR, 0.51; P = .01; 95% CI, 0.30, 0.87). Conclusion: We identified risk factors that may provide guidance for surgeons during preoperative hammertoe surgery consultations. This information may better equip patients with appropriate postoperative expectations when contemplating surgery. Level of Evidence: Level III, retrospective case series.

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FRI0248 PROGNOSTIC FACTORS FOR STEROID-FREE REMISSION IN PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHIES: IMPORTANCE OF ANTHROPOMETRIC MEASUREMENTS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3010 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 708.1-708

Author(s):

J. S. Lee ◽

S. H. Nam ◽

S. J. Choi ◽

W. J. Seo ◽

S. Hong ◽

...

Keyword(s):

Prognostic Factors ◽

Cox Regression ◽

Idiopathic Inflammatory Myopathies ◽

Inflammatory Myopathies ◽

Immunosuppressant Therapy ◽

Muscle Enzymes ◽

Cox Regression Analysis ◽

Factors Associated ◽

Early Use

Background:Several studies have been conducted on factors associated with mortality in idiopathic inflammatory myopathies (IIM), but few studies have assessed prognostic factors for steroid-free remission in IIM.Objectives:We investigated the various clinical factors, including body measurements, that affect IIM treatment outcomes.Methods:Patients who were newly diagnosed with IIM between 2000 and 2018 were included. Steroid-free remission was defined as at least three months of normalisation of muscle enzymes and no detectable clinical disease activity. The factors associated with steroid-free remission were evaluated by a Cox regression analysis.Results:Of the 106 IIM patients, 35 displayed steroid-free remission during follow-up periods. In the multivariable Cox regression analyses, immunosuppressants’ early use within one month after diagnosis [hazard ratio (HR) 6.21, 95% confidence interval (CI) 2.61–14.74, p < 0.001] and sex-specific height quartiles (second and third quartiles versus first quartile, HR 3.65, 95% CI 1.40–9.51, p = 0.008 and HR 2.88, 95% CI 1.13–7.32, p = 0.027, respectively) were positively associated with steroid-free remission. Polymyositis versus dermatomyositis (HR 0.21, 95% CI 0.09–0.53, p = 0.001), presence of dysphagia (HR 0.15, CI 0.05–0.50, p = 0.002) and highest versus lowest quartile of waist circumference (WC) (HR 0.24, 95% CI 0.07–0.85, p = 0.027) were negatively associated with steroid-free remission.Conclusion:The early initiation of immunosuppressant therapy, type of myositis and presence of dysphagia are strong predictors of steroid-free remission in IIM; moreover, height and WC measurements at baseline may provide additional important prognostic value.Disclosure of Interests:None declared

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Long-Term Evaluation of the Roux-Elmslie-Trillat Procedure for Patellar Instability

The American Journal of Sports Medicine ◽

10.1177/0363546504272686 ◽

2005 ◽

Vol 33 (8) ◽

pp. 1220-1223 ◽

Cited By ~ 57

Author(s):

Joseph R. Carney ◽

Timothy S. Mologne ◽

Michael Muldoon ◽

Jay S. Cox

Keyword(s):

Confidence Interval ◽

Case Series ◽

Level Of Evidence ◽

Long Term Effect ◽

Functional Scores ◽

Study Population ◽

Term Evaluation ◽

Subluxation Of The Patella

Background Few published articles exist reporting the long-term evaluation of the Roux-Elmslie-Trillat procedure. Purpose To assess the long-term effect of the Roux-Elmslie-Trillat procedure in preventing recurrent subluxation and dislocation of the patella. Study Design Case series; Level of evidence, 4. Methods Eighteen patients who underwent the Roux-Elmslie-Trillat procedure for dislocation or subluxation of the patella were identified from a group previously evaluated at a mean follow-up of 3 years. The prevalence of recurrent subluxation or dislocation at a mean follow-up of 26 years was compared with the prevalence reported at the mean follow-up of 3 years. Although not the focus of this study, Cox functional scores were obtained from the smaller group and compared with the results at the 3-year follow-up. Results Seven percent (95% confidence interval, 0.00-0.32) of the patients had recurrent subluxation at 26 years compared with 7% (95% confidence interval, 0.03-0.13) of the study population reported at 3 years (P = 1.00). Fifty-four percent (95% confidence interval, 0.27-0.79) rated their affected knee as good or excellent at 26 years compared with 73% (95% confidence interval, 0.64-0.81) of the larger study population reported at 3 years (P = .14). Conclusion The prevalence of recurrent subluxation and dislocation in patients with patellofemoral malalignment who underwent the Roux-Elmslie-Trillat procedure for dislocation or subluxation of the patella is similar at 3 and 26 years after the procedure. The long-term functional status of the affected knee in patients who underwent the Roux-Elmslie-Trillat procedure declined.

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Prevalence of Kidney Injury and Associations with Critical Illness and Death in Patients with COVID-19

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.04780420 ◽

2020 ◽

Vol 15 (11) ◽

pp. 1549-1556 ◽

Cited By ~ 2

Author(s):

Xizi Zheng ◽

Hongyu Yang ◽

Xiaolong Li ◽

Haichao Li ◽

Lingyi Xu ◽

...

Keyword(s):

Critical Illness ◽

Confidence Interval ◽

Cox Regression ◽

Kidney Injury ◽

Hazard Ratio ◽

Secondary Outcome ◽

Cox Regression Analysis ◽

Shenzhen City ◽

Critical Patients

Background and objectivesCoronavirus disease 2019 is spreading rapidly across the world. This study aimed to assess the characteristics of kidney injury and its association with disease progression and death of patients with coronavirus disease 2019.Design, setting, participants, & measurementsThis is a retrospective study. Two representative cohorts were included. Cohort 1 involved severe and critical patients with coronavirus disease 2019 from Wuhan, China. Cohort 2 was all patients with coronavirus disease 2019 in Shenzhen city (Guangdong province, China). Any kidney injury was defined as the presence of any of the following: hematuria, proteinuria, in-hospital AKI, or prehospital AKI. AKI was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) creatinine criteria. The primary outcome was death at the end of follow-up. The secondary outcome was progression to critical illness during the study period.ResultsA total of 555 patients were enrolled; 42% of the cases (229 of 549) were detected with any kidney injury, 33% of the cases (174 of 520) were detected with proteinuria, 22% of the cases (112 of 520) were detected with hematuria, and 6% of the cases (29 of 520) were detected with AKI. Of the 29 patients with AKI, 21 cases were recognized as in-hospital AKI, and eight were recognized as prehospital AKI. Altogether, 27 (5%) patients died at the end of follow-up. The death rate was 11% (20 of 174) in patients with proteinuria, 16% (18 of 112) in patients with hematuria, and 41% (12 of 29) in the AKI settings. Multivariable Cox regression analysis showed that proteinuria (hazard ratio, 4.42; 95% confidence interval, 1.22 to 15.94), hematuria (hazard ratio, 4.71; 95% confidence interval, 1.61 to 13.81), and in-hospital AKI (hazard ratio, 6.84; 95% confidence interval, 2.42 to 19.31) were associated with death. Among the 520 patients with noncritical illness at admission, proteinuria (hazard ratio, 2.61; 95% confidence interval, 1.22 to 5.56) and hematuria (hazard ratio, 2.50; 95% confidence interval, 1.23 to 5.08) were found to be associated with progression to critical illness during the study period.ConclusionsKidney injury is common in coronavirus disease 2019, and it is associated with poor clinical outcomes.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_09_18_CJN04780420.mp3

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PRIMARY LEIOMYOSARCOMA OF BONE: CLINICOPATHOLOGIC AND PROGNOSTIC FACTORS ANALYSIS IN A SINGLE INSTITUTION

Acta Ortopédica Brasileira ◽

10.1590/1413-785220192703215676 ◽

2019 ◽

Vol 27 (3) ◽

pp. 152-155

Author(s):

Juan Pablo Zumárraga ◽

Matheus Manolo Arouca ◽

André Mathias Baptista ◽

Marcelo Tadeu Caiero ◽

Diego Eduardo Rubio ◽

...

Keyword(s):

Prognostic Factors ◽

Bone Tumor ◽

Smooth Muscle Actin ◽

Case Series ◽

Malignant Bone Tumor ◽

Single Institution ◽

Level Of Evidence ◽

Rare Type ◽

Factors Analysis ◽

Primary Leiomyosarcoma

ABSTRACT Objective: Primary leiomyosarcoma of bone (PLB) is a rare type of malignant bone tumor considered as a variant of the spindle cell sarcomas (SCS). The objective of this study was to analyze the clinicopathologic and the prognostic factors of patients with PLB treated at a single institution. Methods: We retrospectively reviewed the records of 22 patients with pathologically confirmed PLB. The data collected were: age, sex, tumor size and location, grade and stage of the disease and histopathologic features. Mean age was 45.5 years (range, 17 to 73 y). Location was: upper limb (27.3%), lower limb (68.2%) and pelvis (4.5%). Patients had high grade in 90.9% of the reports. Margins were negative in 77.3% of the cases. Histological reports describe spindly sarcomatous cells arranged in fascicles with increased vascular formation without osteoid or chondroid matrix production. On immunohistochemistry, smooth muscle actin and desmin where positive in all cases. Results: Mean follow-up time was 73.5 months (range, 5.3 to 331.1 m). We found 22.7% of local recurrence (LR). Distant metastasis (DM) was reported in 9 (40.9%) patients. Lung metastasis was the only DM affected site. Overall survival (OS) rate in 5 years was 59.1%. Predictors of OS were LR and DM. Conclusions: PLB is an extremely rare malignant bone tumor that has a higher rate of DM and similar OS prognosis compared with other bone sarcomas. Level of Evidence IV, Case Series.

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Prognostic factors in patients (pts) with mediastinal nonseminomatous germ cell tumors (MNGCT).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e15585 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e15585-e15585

Author(s):

Anatoly Bulanov ◽

Mikhail Fedyanin ◽

Alexey Tryakin ◽

Ilya Pokataev ◽

Tatiana Zakharova ◽

...

Keyword(s):

Prognostic Factors ◽

Mediastinal Tumor ◽

Cox Regression ◽

Objective Response ◽

Germ Cell Tumors ◽

Residual Tumor ◽

Good Prognosis ◽

Cox Regression Analysis ◽

Prognostic Group

e15585 Background: According to IGCCCG, pts with MNGCT belong to poor prognostic group. But, there are no independent prognostic factors which could determine prognosis in this group of pts. We retrospectively studied prognostic factors in pts with MNGCT. Methods: We analyzed data on 61 pts with MNGCT, who were treated in our department during 1986-2011. Median age was 23 years (range: 18-44). Median follow-up time was 52 months (range 4-180). Biopsy was performed in 35/61 (57.4%) pts before treatment. At the beginning of therapy median AFP was 3,360 IU/ml (range: 1-300,000), HCG – 4.5 mIU/ml (range: 0.1 to 326210), LDH – 791 U/l (range: 249-4,475). Conventional induction chemotherapy (CT): classical BEP regimen – 23 (37.8%) pts, T-BEP – 17 (27.8%) pts, CPOB – 17 (27.8%) pts, accelerated (two-weekly) BEP – 4 (6.6%) pts. After CT, residual tumor was resected in 28 (45.9%) pts. Multivariate Cox regression analysis was performed to determine independent factors, which influenced on overall survival (OS). Results: Marker-negative objective response was revealed in 40/61 (65.6%). Progression disease during induction CT was detected in 21 (34.4%) pts. 5-years OS was 44% for all pts. Multivariate analysis revealed the following independent negative prognostic factors: age ≥ 24 (р=0.08, HR 1.9, 95%CI 0.92-4.1), size of the primary mediastinal tumor ≥ 19 cm (р= 0.03, HR 5.8, 96%CI 1.85-18.67). Median OS hasn’t been reached and 3-year OS was 62% in pts with good prognosis (age < 24 years and/or size of mediastinal tumor < 19 cm) vs. 15 months and 30% in pts with poor prognosis (р=0.02, HR 0.42, 95%CI 0.19-0.87) respectively. Conclusions: Age ≥ 24 and size of the primary mediastinal tumor ≥ 19 cm are independent negative prognostic factors in pts with MNGCT. These factors could be used as strata in clinical trials. However, this tendency has to be confirmed in large series of pts.

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Predictors of recurrence in patients with surgically resected pancreatic neuroendocrine tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.408 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 408-408

Author(s):

Cynthia Harris ◽

Michelle Kang Kim ◽

Kiwoon Joshua Baeg ◽

Mi Ri Lee ◽

Julie Starr ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Cox Regression ◽

Disease Free Survival ◽

Tumor Grade ◽

Disease Recurrence ◽

Stage Ii ◽

Pancreatic Neuroendocrine Tumors ◽

Cox Regression Analysis ◽

Grade 3

408 Background: Current surveillance guidelines regarding follow up of patients with resected pancreatic neuroendocrine tumors (PNETs) are based on limited data, and there have been few studies evaluating recurrence risk in such patients. We assessed disease-free survival (DFS) in a large, multi-institutional cohort of patients with resected PNETs. Methods: Patients with surgically resected, non-metastatic PNETs between 1990-2017 were identified using institutional databases at three institutions: Mount Sinai Hospital, Dana-Farber Cancer Institute, and University of Pennsylvania. Recurrence date was defined as the imaging date documenting first recurrence (n = 56); if an imaging date was not available, then July 1 of that year was used in calculations (n = 9). Kaplan-Meier analysis was used to estimate DFS; multivariate Cox regression analysis was used to assess DFS adjusted for patient and disease-related characteristics, including tumor stage and grade. Results: We identified a total of 418 patients with surgically resected, non-metastatic PNETs between 1990-2017. Of these patients, 299 patients had complete stage and tumor grade information and were used for subsequent analysis. Patients were 48.6% male with a median age of 57.5 years at time of surgery. The distribution of AJCC stage and grade was as follows: 170 (56.9%) patients were stage I, 129 (43.1%) were stage II; 167 (55.9%) had grade 1, 121 (40.5%) had grade 2, and 11 (3.7%) had grade 3 tumors. Median follow-up was 2.6 years (interquartile range = 4.2); during this time, 65 (21.7%) patients developed disease recurrence. After adjusting for potential confounders, patients with more advanced stage and higher tumor grade were significantly more likely to develop disease recurrence (Hazard Ratio (HR): 6.9, 95% CI: 2.5-19.1 for stage II; HR 4.0 (1.7-9.5) for grade 2; HR 2.6 (0.4-17.8) for grade 3). Both higher stage and tumor grade were associated with decreased DFS (p < 0.0001 for both). Conclusions: In surgically resected PNETs, with a median follow-up time of 2.6 years, both higher stage and higher grade are associated with decreased DFS. Further follow up of this cohort is planned.

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The influence of obesity on tumor recurrence in vulvar cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e17130 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e17130-e17130 ◽

Cited By ~ 1

Author(s):

Rüdiger Klapdor ◽

Peter Hillemanns ◽

Linn Lena Woelber ◽

Julia Kathrin Jueckstock ◽

Felix Hilpert ◽

...

Keyword(s):

Cancer Patients ◽

Vulvar Cancer ◽

Cox Regression ◽

Univariate Analysis ◽

Disease Free Survival ◽

Tumor Grade ◽

Tumor Stage ◽

Tumor Diameter ◽

Cox Regression Analysis

e17130 Background: Obesity is associated with worse patients’ survival in several cancer entities. Vulvar cancer as well as obesity show increasing incidence over the last years. The influence of obesity on prognosis of vulvar cancer patients is not clear. However, knowledge about this may have consequences on prevention, treatment, and follow-up. Methods: This is an analysis of the large AGO-CaRE-1 study. Patients suffering from squamous cell vulvar cancer (UICC stage IB and higher), treated in 29 cancer centers between 1998 and 2008, were categorized in a database, in order to analyze treatment patterns and prognostic factors in a retrospective setting. Results: In total, 849 patients with documented height and weight were divided into two groups depending on their body mass index (BMI, < 30 vs. ≥30 kg/m²). There was no difference in the baseline variables (age, tumor diameter, depth of infiltration, tumor stage, nodal invasion, tumor grade) between both groups (p > 0.05). However, we identified differences regarding ECOG status and preexistent comorbidities (cardiovascular, dementia) towards healthier patients with BMI < 30 kg/m². Treatment variables (R0 resection, chemotherapy, radiotherapy, continuation of adjuvant therapy) did not differ (p > 0.05). Patients with BMI ≥30 kg/m² underwent radical vulvectomy more often (61.1 % vs. 51.8%, p = 0.042). During follow-up, there was a higher recurrence rate in the group having a BMI ≥30 kg/m² (43.4%, vs. 28.3%, p < 0.01) due to an increased rate of local recurrences (33.3% vs. 18.5%, p < 0.01). The rate of groin and distant recurrences was similar between both groups (p > 0.05). Noteworthy, we observed a significantly shorter disease free survival (DSF) of the obese patients in univariate analysis (HR 1.362, 95%CI 1.093-1.696, p = 0.006). Even in multivariate Cox-regression analysis including age, ECOG, tumor stage, type of surgery, nodal invasion, tumor grade, and comorbidities patients with BMI ≥30 kg/m² had a significantly shorter DFS (HR 1.811, 95%CI 1.005-3.262, p = 0.048). Conclusions: In this first large study about the association between obesity and prognosis of vulvar cancer patients, we observed that a BMI ≥30kg/m² was associated with shorter DFS, mainly attributed to a higher risk for local recurrence.

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Prognostic Factors for Myelodysplastic Syndrome in the Veteran Population: Single Institution Experience.

Blood ◽

10.1182/blood.v110.11.4622.4622 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4622-4622

Author(s):

Michael Axelson ◽

Shirisha Reddy ◽

Crystal Lumby ◽

Sue Sivess-Franks ◽

Jonathan Dowell ◽

...

Keyword(s):

Overall Survival ◽

Multivariate Analysis ◽

Prognostic Factors ◽

Blood Transfusion ◽

Cox Regression ◽

Medical Center ◽

Univariate Analysis ◽

Single Institution ◽

Number Of Patients

Abstract Background: Myelodyplastic syndrome (MDS) is the disease of the elderly and increasingly common in the veteran population. Here we report a single institution experience with MDS at the Dallas VA Medical Center. Patients and Method: From a period of 1998–2007, eighty three pts were identified out of which 54 pts had bone marrow (BM) biopsy proven diagnosis of MDS. Overall survival (OS) analysis with dependent variables (Age at diagnosis, IPSS Score, WHO morphologic diagnosis, number of blood and platelet transfusions required, Hb level, ANC, cytogenetics, blast percentage, BM cellularity at diagnosis) were conducted by selection method “foreward” and only these significant variables were used in the Cox regression for multivariate analysis. Methods of Kaplan and Meier were used to generate OS curves. Results: The median age of diagnosis was 74 yrs with a median follow up time of 12.5 months. The WHO morphologic subtype was RA/RARS (n=13), Del5q (n=1), RCMD/RCMDRS (n=34), RAEB1 (n=3), RAEB2 (n=1), missing (n=2). The distribution of IPSS score was 0 (n=25); 0.5 (n=15); 1.0 (n=8), 1.5 (n=4), missing (n=2). Five pts had treatment related MDS and 3 pts transformed to AML. One patient had concurrent MGUS and one patient developed multiple myeloma. At diagnosis, 23 pts had a hemoglobin (Hb) value of less than 10g/dl. Only 4 pts had ANC less than 500; sixteen pts had ANC 500–1800 and 34 pts had normal counts. A majority of pts had normal cytogenetics (n=37), 5 pts had good risk, 5 pts had intermediate risk and 7 pts had poor risk cytogenetics. Six pts had hypocellular (<30%) BM at diagnosis whereas 16 pts had a hypercellular marrow (> 50%). Only 4 pts had more than 5% blast in the BM. Twenty nine pts eventually became blood transfusion dependent and 12 pts needed platelet transfusion at some point. Thirty six pts were treated with erythropoietin (with or without neupogen) and 13 pts received some type of disease modifying therapy (5-azacytidine/lenalidomide/ATG/clinical trial). The mean survival time was 106 months. Median survival was not reached at the time of analysis. In the univariate analysis, IPSS score (p=0.003), No. of blood transfusions (p=0.028), cytogenetics (p=0.0001) and blast percentage (p=0.0015), were statistically significant. BM cellularity (p=0.06) and Hb level (p=0.09) showed a trend towards significance. On multivariate analysis, Hb greater than 10 (HR 0.08; p=0.011), abnormal cytogenetics (HR 4.2; p=0.001), BM Blast > 5% (p=0.026) and BM cellularity < 30% (HR 4.6; p=0.033) emerged as the significant predictors of overall survival. IPSS score or Blood transfusion requirement did not pan out to be significant. Conclusion: MDS in the veteran population may be different from general population and may have unique predictors of survival. A larger number of patients and longer duration of follow up is required to further evaluate these prognostic factors.

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Gene-Expression for Prediction of Disease Progression Following Initial Management of Follicular Lymphoma

Blood ◽

10.1182/blood.v126.23.4804.4804 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4804-4804

Author(s):

Etienne Mahe ◽

Ariz Akhter ◽

Danielle H. Oh ◽

Fahad Farooq ◽

Meer-Taher Shabani-Rad ◽

...

Keyword(s):

Follicular Lymphoma ◽

Regression Model ◽

Disease Progression ◽

Cox Regression ◽

Tumor Grade ◽

Age At Diagnosis ◽

P Value ◽

Cox Regression Model ◽

Cox Regression Analysis

Abstract Introduction Patients with advanced staged Follicular Lymphoma (FL) are initially managed with either immediate chemoimmunotherapy (CI) or "watchful waiting" (WW) depending on clinical symptoms, tumor burden, and organ compromise. Clinicians currently predict time to progression (TTP) using the Follicular Lymphoma International Prognostic Index (FLIPI) score. Well-defined & validated molecular techniques capable of additional predictive power are lacking, however. We hypothesized that gene-expression (GE) data, employing an evidence-based feature set, might assist in the upfront stratification of FL patients. Objectives 1 Identify genes whose GE has previously been identified as relevant to FL 2 Perform GE testing on an series of FL cases, classified by upfront intervention, using this custom gene feature set 3 Identify the gene(s) most strongly predictive of disease progression in each of the clinical classes (i.e. CI vs. WW) 4 Compare the performance of GE data to other prognostic parameters Methods We performed a search of MEDLINE-indexed studies reporting FL GE results. We input all available appertaining data into NVIVO (v10), in which a computer-assisted search for GE features was performed. This list, after refinement, formed the basis of a custom NanoString codeset. We used the MD Anderson Microarray Sample Size Calculator for sample size estimation and retrieved FL cases from our regional archives; those cases with sufficient tissue were organized by upfront treatment approach and available clinical data recorded (age at diagnosis, sex, stage, grade, FLIPI scores & TTP). TTP was defined as time in months either to diagnosed disease progression or, in the WW group, first CI-based treatment. After pathology review, RNA was isolated using standard protocols. GE data was analyzed using gene-specific receiver-operating characteristic analysis, ranking performed according to the area-under-the-curve (MATLAB v 8.3.0.532). Validation against TTP using Cox-regression was then performed (SPSS v22); p < 0.05 was considered significant. Results Our MEDLINE search yielded 713 publications; after refinement, our NVIVO analysis suggested 282 valid gene features. Review of local FL cases accessioned between 2004 & 2012 was performed; this period ensured uniform follow-up and CI treatment strategies for all FL patients. Patients were classified as WW (68 patients) & CI (98 patients), and then sub-classified as WW1 (WW without need for CI over the follow-up interval; 23 patients) and WW2 (WW requiring CI in the follow-up interval; 45 patients) and CI1 (CI without disease progression over the follow-up interval; 61 patients) and CI2 (CI with disease progression; 37 patients). Median follow-up time was 60 months in the WW group and 56 months in the CI group (Mann-Whitney p = 0.177). With the exception of FLIPI score in the WW class (higher on average in the WW2 sub-class), no other clinical factor differed significantly between the sub-classes. GE analyses suggested that ACTB in the WW group and MEK1 in the CI group might be most predictive of TTP. Table 1. TTP results by Cox-regression analysis for the WW group WW Variable Cox-Regression Model Co-efficient p-value Cox-Regression Model Linear Co-efficient 95% CI Age at diagnosis 0.56 0.98-1.04 Sex 0.34 0.67-3.19 Tumor Grade 0.41 0.40-9.48 Tumor Stage 0.54 0.69-2.04 FLIPI Score 0.06 0.97-3.6 ACTB Expression 0.006 1.4-7.74 Table 2. TTP results by cox-regression analysis for the CI group CI Variable Cox-Regression Model Co-efficient p-value Cox-Regression Model Linear Co-efficient 95% CI Age at diagnosis 0.34 0.99-1.04 Sex 0.96 0.48-2.16 Tumor Grade 0.92 0.43-2.13 Tumor Stage 0.17 0.874-2.11 FLIPI Score 0.4 0.47-1.35 MEK1 Expression 0.011 0.19-0.81 Conclusions To our knowledge, we have performed the first GE analysis of FL cases classified by intervention, and have identified GE features predictive of disease progression or requirement of intervention (as in the WW group). In the CI group, identification of MEK1 as a major prognostic player echoes previous work studying the MAP-kinase pathway in FL. In the WW group, however, identification of ACTB as a potential prognostic player is a novel observation requiring validation, especially since this gene is ubiquitously expressed across multiple cell types. Figure 1. WW TTP, stratified by ACTB expression Figure 1. WW TTP, stratified by ACTB expression Figure 2. CI TTP, stratified by MEK1 expression Figure 2. CI TTP, stratified by MEK1 expression Disclosures No relevant conflicts of interest to declare.

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