Factors For Progression In Patients Research Articles

Genomic profiling of mycosis fungoides identifies patients at high risk of disease progression

AbstractMycosis fungoides (MF) is the most prevalent primary cutaneous T-cell lymphoma, with an indolent or aggressive course and poor survival. The pathogenesis of MF remains unclear, and prognostic factors in the early stages are not well established. Here, we characterized the most recurrent genomic alterations using whole-exome sequencing of 67 samples from 48 patients from Lille University Hospital (France), including 18 sequential samples drawn across stages of the malignancy. Genomic data were analyzed on the Broad Institute’s Terra bioinformatics platform. We found that gain7q, gain10p15.1 (IL2RA and IL15RA), del10p11.22 (ZEB1), or mutations in JUNB and TET2 are associated with high-risk disease stages. Furthermore, gain7q, gain10p15.1 (IL2RA and IL15RA), del10p11.22 (ZEB1), and del6q16.3 (TNFAIP3) are coupled with shorter survival. Del6q16.3 (TNFAIP3) was a risk factor for progression in patients at low risk. By analyzing the clonal heterogeneity and the clonal evolution of the cohort, we defined different phylogenetic pathways of the disease with acquisition of JUNB, gain10p15.1 (IL2RA and IL15RA), or del12p13.1 (CDKN1B) at progression. These results establish the genomics and clonality of MF and identify potential patients at risk of progression, independent of their clinical stage.

Long term outcome and prognostic indicators in Posner Schlossman syndrome.

Posner Schlossman syndrome is a well-defined uveitis entity that is characterised by relapsing remitting unilateral anterior uveitis with markedly raised intraocular pressure. The aim of this study was to determine the risk factors for progression in patients with Posner Schlossman syndrome. Ninety-eight patients were enrolled in a retrospective case series. Progression was defined as a composite endpoint of any of development of permanent glaucoma (in patients with no evidence of glaucomatous loss on presentation), corneal failure, or chronic inflammation. Relapse was defined as a resolving episode of inflammation not meeting the criteria for progression. Seventy seven percent of patients relapsed on average each 2.2 years. Forty percent of patients progressed. On univariate analysis, increased age at enrolment, immunocompromise at enrolment, the presence of glaucomatous optic neuropathy at enrolment, the performance of an anterior chamber tap and a positive anterior chamber tap were all associated with increased risk of progression. On multivariate analysis, age at enrolment, immunocompromise at enrolment, the performance of an anterior chamber tap, and the presence of glaucomatous optic neuropathy at enrolment were independently associated with increased risk of disease progression. Posner Schlossman syndrome is not a benign uveitis entity and risk of both relapse and progression are high. Older patients, immunocompromised patients, patients with glaucomatous optic neuropathy at enrolment and those with a positive anterior chamber tap are all at increased risk of progression.

Risk Factors for Progression in Patients Undergoing Surveillance for Pancreatic Cysts.

To identify risk factors associated with the progression of pancreatic cysts in patients undergoing surveillance. Previous studies of intraductal papillary mucinous neoplasms (IPMNs) rely on surgical series to determine malignancy risk and have inconsistently identified characteristics associated with IPMN progression. We conducted a retrospective review of 2197 patients presenting with imaging concerning for IPMN from 2010 to 2019 at a single institution. Cyst progression was defined as resection or pancreatic cancer development. The median follow-up time was 84 months from the presentation. The median age was 66 years, and 62% were female. Ten percent had a first-degree relative with pancreatic cancer, and 3.2% had a germline mutation or genetic syndrome associated with an increased risk of pancreatic ductal adenocarcinoma (PDAC). Cumulative incidence of progression was 17.8% and 20.0% at 12 and 60 months postpresentation, respectively. Surgical pathology for 417 resected cases showed noninvasive IPMN in 39% of cases and PDAC with or without associated IPMN in 20%. Only 18 patients developed PDAC after 6 months of surveillance (0.8%). On multivariable analysis, symptomatic disease [hazard ratio (HR)=1.58; 95% CI: 1.25-2.01], current smoker status (HR=1.58; 95% CI: 1.16-2.15), cyst size (HR=1.26; 95% CI: 1.20-1.33), main duct dilation (HR=3.17; 95% CI: 2.44-4.11), and solid components (HR=1.89; 95% CI: 1.34-2.66) were associated with progression. Worrisome features on imaging at presentation, current smoker status, and symptomatic presentation are associated with IPMN progression. Most patients progressed within the first year of presentation to Memorial Sloan Kettering Cancer Center (MSKCC). Further investigation is necessary to develop personalized cyst surveillance strategies.

Risk Factors for the Progression of Varus Ankle Osteoarthritis.

With the increase in life expectancy, the prevalence of ankle osteoarthritis (OA) is also expected to increase in the future. Functional disability and diminished quality of life associated with end-stage ankle OA are comparable to those associated with end-stage hip or knee OA. However, there are few reports on the natural history and progression of patients with ankle OA. Hence, this study aimed to evaluate the risk factors for progression in patients with varus ankle OA. We evaluated 68 ankles from 58 patients diagnosed with varus ankle OA using radiography performed at intervals over at least 60 months. The mean follow-up period was 99 ± 40 months. Narrowing of the joint space and increasing osteophyte formation were defined as ankle OA progression. Multivariate analysis was performed using logistic regression to predict the odds of progression; the model included 2 clinical variables and 7 radiographic variables. Of the 68 ankles, 39 (57%) progressed. In multivariable logistic regression analyses, patient's age (odds ratio [OR] 0.92, 95% CI 0.85-0.99, P < .03), and the talar tilt (TT; OR 2.2, 95% CI 1.39-3.42, P = .001) were found to be independent factors for progression. The area under the curve (AUC) of the receiver operating characteristic curve for TT was 0.844, and the cutoff value was 2.0 degrees. TT was found to be a primary factor associated with varus ankle OA progression. The risk appeared higher in patients with a TT more than 2.0 degrees. Level III, retrospective case control study.

Prognostic significance of neutrophil to lymphocyte ratio in patients with metastatic breast cancer on the background of eribulin therapy

Background. The neutrophil to lymphocyte ratio (NLR) is a prognostic marker in various carcinomas, including breast cancer. The NLR reflects the balance of systemic immunity and is associated with survival in patients with solid tumors.Aim. This study retrospectively evaluated the significance of the NLR and the absolute lymphocyte count in patients with breast cancer who received eribulin therapy.Materials and methods. The prognostic significance of the NLR and the absolute lymphocyte count in 33 patients with metastatic breast cancer treated with eribulin in 2020–2021 was analyzed.Results. The median follow-up time for patients was 9 [6; 15] months. Twenty-six of 33 (78.8 %) patients progressed. Seven of 33 (21.2 %) patients were censored due to therapy discontinuation, complete discontinuation after 1 course was required in 3 (9.1 %) patients and was associated with the development of hematological toxicity: 1 (3 %) case of a combination of grade 3 leucopenia and grade 3 thrombocytopenia, 2 (6 %) cases of grade 3 neutropenia. According to the analysis results, the NLR was a statistically significant risk factor for progression in patients on eribulin therapy, both without taking into account the influence of other factors (univariate model) and with the underlying influence of the absolute neutrophil count and the absolute lymphocyte count: hazard ratio (95 % confidence interval) was 1.21 [1.04; 1.41], p = 0.015 and 1.30 [1.07; 1.57], p = 0.008, respectively. There was no statistically significant effect of the absolute neutrophil count and the absolute lymphocyte count in both univariate and multivariate models. To illustrate the impact of SNL on the onset of progression, patients were divided into two subgroups based on median SNL: SNL˂ 2.46 and SNL ≥2.46. The median survival in patients with SNL ≥2.46 was 9 months, and in patients with SNL˂ 2.46 it was 15 months.Conclusion. The results of the pilot study state the NLR is a potential prognostic marker of long-term treatment with eribulin for patients with metastatic breast cancer, and can be used in clinical practice.

Effect of obesity on time to progression in patients with resectable and potentially resectable pancreatic cancer.

e16246 Background: Obesity has been identified as a risk factor for pancreatic cancer. The prevalence of obesity has been on a rise in the last two decades. Obesity is defined by the world health organization (WHO) as body mass index (BMI) &gt; 30.0 kg/m2. Studies have shown obese patients to have worse survival than non-obese patients with pancreatic cancer. However, there is limited data on effect of obesity on disease progression. We sought to identify the relationship between obesity and time to progression in patients with resectable and potentially resectable pancreatic ductal adenocarcinoma (PDAC). Methods: We performed a retrospective review of charts of all patients diagnosed with PDAC from 2017-2019 at Allegheny Health Network. Demographics (including age, sex, and race), treatment details, and time to progression date of diagnosis (rounded off in months) were obtained. Two-sided Mann-Whitney U test and Fischer’s exact test were used to evaluate differences between groups with continuous and categorical variables respectively. Furthermore, paired t test was used to compare mean time to progression between the patients in the obese and non-obese groups. A p-value of &lt; 0.05 was considered as level of significance. Results: Out of the 121 patients who received treatment at our institution, 40 patients who had resectable or potentially resectable disease and had progression of disease were included in the analysis. The median age of patients was 68. The majority were females (60%), Caucasians (90%), had Stage I (65%) and potentially resectable disease (55%). Around 70% of patients were treated surgically, 80% received chemotherapy and 26% received radiation therapy. Twelve out of 42 patients were obese (27.5%). No difference in patient characteristics including demographics, staging, and treatment characteristics (proportion of patients who received surgery, chemotherapy, and radiotherapy) was identified between obese and non-obese group patients. The mean time to progression was 11.9 months in obese group as compared to 13.7 months in non-obese group (p = 0.63). Conclusions: Our study showed no significant difference in time to progression of disease between obese and non-obese patients with resectable/potentially resectable pancreatic cancer. Our study is limited by its small sample size, retrospective nature, and unidentifiable confounding factors that could potentially affect outcomes. Larger scale studies are needed to investigate the effect of obesity as a prognostic factor for disease progression in patients with pancreatic cancer.

MO222: Prognostic Factors for CKD Progression in Patients with IGA Nephropathy

Abstract BACKGROUND AND AIMS IgA nephropathy is a progressive renal disease with up to 30% of patients reaching end stage kidney disease within 10–20 years. The aim of this study was to analyze the phenotype of patients with IgA nephropathy followed in a tertiary renal center and explore its association with renal survival. METHOD All records from patients with a biopsy-proven IgA nephropathy were retrospectively assessed. Demographic and clinical characteristics were recorded for each patient at baseline and during follow-up. The transition to the next stage of chronic kidney disease (CKD) by the end of the follow-up was considered as progression of CKD. RESULTS We included 53 patients with IgA nephropathy, 35 (66.04%) males and 18 (33.96%) females. The mean age at the time of diagnosis was 46 (±16.92) years old and the median follow-up time was 4.75 (2–11.75) years. Median eGFR using the CKD-EPI creatinine equation was 63 (32–86) mL/min/1.73 m2 and the median proteinuria level was 1890 (830–3500) mg/24 h. At the time of diagnosis, 30.19% of patients presented with macroscopic hematuria, 24.53% with upper respiratory infection, 11.32% with rapidly progressive glomerulonephritis and 60.38% with hypertension. The majority (86.7%) of patients were treated with renin–angiotensin–aldosterone system (RAAS) blockade, while 34 patients (64.15%) received immunosuppression. Eighteen patients (33.96%) were treated with a 6-month corticosteroid regimen (Pozzi protocol), seven (13.21%) with cyclophosphamide, four (7.55%) with azathioprine and eleven (20.75%) with mycophenolate mofetil, while seven patients (13.21%) received repeated therapeutic regimens. The level of proteinuria (g/24h) and the need for repeated therapy were prognostic factors of CKD progression at the end of the follow-up (HR 1.22, P = .01 and HR 2.90, P = .04, respectively). In age-adjusted multivariable analysis only the need for repeated therapy remained statistically significant. The patients who needed repeated treatment had a 4.45-fold risk for CKD progression compared with patients of the same age, who did not need repeated therapy (HR 4.45, P = .02). CONCLUSION High grade proteinuria and mainly the need for repeated treatment are poor prognostic factors of CKD progression during the long-term follow up of patients with IgA nephropathy.

Associations of serum levels of microRNA-371a-3p (M371) with risk factors for progression in nonseminomatous testicular germ cell tumours clinical stage 1

PurposeLymphovascular invasion (LV1) and presence of > 50% embryonal carcinoma (> 50% EC) represent risk factors for progression in patients with clinical stage 1 (CS1) nonseminomatous (NS) testicular germ cell tumours. As serum levels of microRNA-371a-3p (M371) are capable of detecting small amounts of GCT, we evaluated if LV1 and > 50% EC are associated with M371 levels.MethodsM371 serum levels were measured postoperatively in 153 NS CS1 patients and both pre- and postoperatively in 131 patients. We registered the following factors: age, tumour size, LV status, > 50% EC, teratoma in primary, preoperative elevation of classical tumour markers. M371 expression was compared among subgroups. The ability of M371 to predict LV1 was calculated by receiver operating characteristics (ROC) curves. Multiple regression analysis was used to look for associations of M371 levels with other factors.ResultsPostoperatively elevated M371 levels were found in 29.4% of the patients, but were neither associated with LV status nor with > 50% EC. Likewise, relative decrease of M371 was not associated. ROC analysis of postoperative M371 levels revealed an AUC of 0.5 for the ability to predict LV1 while preoperative M371 had an AUC of 0.732. Multiple regression analysis revealed significant associations of preoperative M371 levels with LV status (p = 0.003), tumour size (p = 0.001), > 50% EC (p = 0.004), and teratoma component (p = 0.045).ConclusionPostoperatively elevated M371 levels are not associated with risk factors for progression in NS CS1 patients. However, the significant association of preoperative M371 expression with LV1 deserves further evaluation.

Risk scoring system for recurrence after simultaneous resection of colorectal cancer liver metastasis.

BackgroundThe simultaneous resection of synchronous colorectal cancer liver metastasis (SCRLM) has been widely applied. It is necessary to establish a risk scoring system to predict post-operative recurrence, especially in patients with neoadjuvant treatment.MethodsThe medical records of 221 patients undergoing simultaneous resection of CRLM were assessed in this study with a further 128 patients allocated to a validation group. All patients in the study group were classified according to their history of neoadjuvant treatment and univariate and multivariate analyses were applied to study independent risk factors. A score model was then generated according to the factors included. Our data set were also applied to validate three other existing scoring models [Fong clinical recurrence score (CRS), Konopke, and Zakaria disease-free survival (DFS) score], and the concordance index was calculated for comparison among these models.ResultsCRLM involving more than three nodes positive for a primary tumor was considered an independent risk factor for progression in patients without neoadjuvant treatment and all score models could discretely stratify patients according to disease free survival. In patients receiving neoadjuvant treatment, CRLM involving more than one node and transfusion invasion were major determinants in patients after treatment. However, only our scoring system and Fong’s CRS score could discretely discriminate patients. In the validation group, patients were significantly classified with the score system.ConclusionsExisting score models had better values for determining prognosis in patients with SCRLM, especially in those undertaking neoadjuvant treatment. Larger cohorts, along with more detailed clinical features and multicenter validation should be undertaken before utilization.

Prognostic factors for progression in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia in complete molecular response within 3 months of therapy with tyrosine kinase inhibitors.

The achievement of a 3-month complete molecular response (CMR) is a major prognostic factor for survival in patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). However, 25% of patients relapse during therapy with tyrosine kinase inhibitors (TKIs). The authors reviewed 204 patients with Ph-positive ALL who were treated between January 2001 and December 2018 using the combination of hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) plus a TKI (imatinib, 44 patients [22%]; dasatinib, 88 patients [43%]; or ponatinib, 72 patients [35%]). Progression-free survival (PFS) was defined as the time from the start date of therapy to the date of relapse, death, or last follow-up. Overall survival (OS) was defined as the time from the start date of therapy to the date of death or last follow-up. Overall, a 3-month CMR was observed in 57% of patients, including 32% of those who received imatinib, 52% of those who received dasatinib, and 74% of those who received ponatinib. The median follow-up was 74 months (imatinib, 180 months; dasatinib, 106 months; ponatinib, 43 months). Among 84 patients in 3-month CMR, 17 (20%) proceeded to undergo allogeneic stem cell transplantation (ASCT). The 5-year PFS and OS rates were 68% and 72%, respectively. By multivariate analysis, ponatinib therapy was the only significant favorable independent factor predicting for progression (P = .028; hazard ratio, 0.388; 95% CI, 0.166-0.904) and death (P = .042; hazard ratio, 0.379; 95% CI, 0.149-0.966). ASCT was not a prognostic factor for PFS and OS by univariate analysis. In patients with Ph-positive ALL, ponatinib is superior to other types of TKIs in inducing and maintaining a CMR, thus preventing disease progression. ASCT does not improve outcome once a 3-month CMR is achieved.

Prognostic Factors for Radiographic Progression in Patients with Seronegative Rheumatoid Arthritis.

(1) Background: It has long been suggested that seronegative rheumatoid arthritis (RA) represents a clinical entity quite distinct from that of seropositive. However, analytical studies of seronegative RA dedicated to clinical outcomes regarding radiographic progression and related risk factors are scarce. The aim of this study is to evaluate radiographic outcome and prognostic factors for radiographic progression in patients with seronegative rheumatoid arthritis. (2) Methods: Subjects included RA patients reported as seronegative for both rheumatoid factor and anti-citrullinated protein antibody, who were treated at Jeju National University Hospital in South Korea between 2003 and 2016, including follow-up of at least 2 years. All patients fulfilled 1987 ACA or 2010 ACR/EULAR RA criteria. Radiographic progression was measured by yearly change in the Sharp van der Heijde (SvdH) score during follow-up periods. Medical records, laboratory and radiographic data were retrospectively analyzed, and linear regression analysis was performed to evaluate prognostic factors for radiographic progression in patients with seronegative rheumatoid arthritis. (3) Results: In total, 116 patients with seronegative RA were observed and 43 (37.1%) patients demonstrated radiographic damage during follow-up period. Mean age at diagnosis was 48 years and 86 (74.1%) patients were female. Symptom duration at diagnosis was 1.3 years and mean follow-up duration was 5.2 years. Patients with radiographic damage at diagnosis were 14 (12.1%) and mean SvdH score was 6.8 at diagnosis. Radiographic damage and SvdH at diagnosis significantly correlated with radiographic progression in patients with seronegative RA after adjusting age, sex, symptom duration, number of active synovitis, and CRP at diagnosis (β-coefficient 6.5 ± 1.84; p = 0.001 and β-coefficient 0.12 ± 0.02; p < 0.001, respectively). (4) Conclusions: This study determined that radiographic damage and SvdH at diagnosis were predictive factors in progression of radiographic damage in patients with seronegative rheumatoid arthritis. A large comparative study dedicated to this issue in seronegative RA is required.

Determination of risk factors for progression in patients with viable tumor at post-chemotherapy lymph node dissection due to disseminated non-seminomatous germ-cell tumors.

To assess the clinical variables that effect progression in patients with viable tumor after post-chemotherapy lymph node dissection due to disseminated non-seminomatous germ-cell tumors. We performed a retrospective analysis of 32 patients with viable tumor after PC-RPLND, operated between 1990 and 2016. Patients were categorized into 2 groups as favorable and non-favorable (intermedia and poor) according to International Germ Cell Consensus Classification (IGCCC). Tumor size was determined as the largest dimension of retroperitoneal mass. Clinical factors and adjuvant chemotherapy were evaluated to impact on recurrence free survival (RFS) and overall survival (OS). The median age of the patients and follow-up duration were 28.5 (17-51) years and 51.5 (4-253) months, respectively. 5-year RFS and OS were 57.8-66.8%, respectively. On univariate analysis, percentage of viable tumor, IGCCC risk group, primary site, second-line chemotherapy and surgical margin status were significant for RFS (p = 0.034, p = 0.002, p < 0.001, p = 0.011 and p < 0.001, respectively), while IGCCC risk group, second-line chemotherapy and surgical margin status were significant for OS (p = 0.004, p = 0.010 and p < 0.001, respectively). On multivariate analysis, second-line chemotherapy and surgical margin were independent risk factors for RFS (p = 0.016, HR 4.927 95% CI 1.34-18.02 and p < 0.001, OR 9.147 95% CI 2.61-31.98, respectively) and surgical margin status was the only predictor of OS (p = 0.038, HR 3.874 95% CI 1.07-13.69). Retroperitoneal lymph node dissection with negative surgical margin is essential for patients with viable residual tumor after chemotherapy. Need for second-line chemotherapy shows risk of progression.

Abstract 3162: Early change in peripheral blood CD4+T cells associated with the clinical outcome in gastrointestinal cancer patients receiving immune checkpoint inhibitors

Abstract Purpose: Predictive biomarkers for immune checkpoint inhibitors (ICIs) are urgently needed in advanced gastrointestinal (GI) carcinoma. Methods: Peripheral blood lymphocyte, lymphocyte subset and early dynamic changes of them were retrospectively analyzed in patients with GI cancer treated with ICIs. Cox regression and Kaplan-Meier analyses were conducted to analyze survival. Results: Eighty patients were enrolled. According to whether tumor progression occurred by 6 months after the initial ICI, patients were divided into two cohorts, 6m-progressive disease (PD) (N=40) and 6m-non-PD (nPD) (N=40).BaselineCD4+/CD8+ T cell (CD4/CD8) ratio was higher in the 6m-nPD cohort than in the 6m-PD cohort. Lymphocyte subsets were obtained both at baseline and before the second dose of ICIs in 61 patients. In total, 54.1% (33/61) of patients experienced tumor progression within 6 months of the initial ICI treatment, and these patients showed significant declines in CD4+ T cell counts (CD4-C1-decline) (p=0.0002) and the CD8+ T cell counts (CD8-C1-decline) (p=0.045) after the first dose of ICIs. In multivariate analyses, CD4-C1-decline (HR=12.66; 95% CI: 2.17-73.91; p=0.005) was an independent prognostic factor for OS. Furthermore, Stratified analyses indicated that CD4-C1-decline was a poor prognostic factor for tumor progression in patients with a deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H). Conclusion: Early change in CD4+ T cell counts in peripheral blood samples may help as prognostic biomarkers for GI cancer patients treated with ICIs. Further prospective studies are needed to validate this conclusion. Citation Format: Zhi-Hao Lu, Chang Liu, Yan-ni Wang, Shuang Li, Xi Jiao, Jian-ling Zou, Zheng-hang Wang, Chang-song Qi, Xiao-tian Zhang, Jian Li, Lin Shen. Early change in peripheral blood CD4+T cells associated with the clinical outcome in gastrointestinal cancer patients receiving immune checkpoint inhibitors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3162.

Prognostic Factors for Progression in Patients (pts) with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ALL) in Complete Molecular Response (CMR) within 3 Months of Therapy with Tyrosine Kinase Inhibitors (TKIs)

Prognostic Factors for Progression in Patients (pts) with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ALL) in Complete Molecular Response (CMR) within 3 Months of Therapy with Tyrosine Kinase Inhibitors (TKIs)

FRI-333-ATG7 genetic variant and defective autophagy: A novel risk factor for non-alcoholic fatty liver disease progression in patients with type 2 diabetes mellitus

FRI-333-ATG7 genetic variant and defective autophagy: A novel risk factor for non-alcoholic fatty liver disease progression in patients with type 2 diabetes mellitus

ATG7 genetic variant and defective autophagy: a novel risk factor for non-alcoholic fatty liver disease progression in patients with type 2 diabetes mellitus

ATG7 genetic variant and defective autophagy: a novel risk factor for non-alcoholic fatty liver disease progression in patients with type 2 diabetes mellitus

Raf1 is a prognostic factor for progression in patients with non‑small cell lung cancer after radiotherapy.

Raf-1 proto-oncogene, serine/threonine kinase (Raf1) acts as a part of the RAS/RAF/MEK/ERK signaling pathway and regulates cell migration, apoptosis and differentiation. However, few studies are available on the expression and clinical significance of Raf1 in non‑small cell lung cancer (NSCLC). This study investigated the clinical value and prognostic significance of Raf1 in NSCLC patients, following radiotherapy. We evaluated the Raf1 expression using immunohistochemical analyses of samples from 110 NSCLC patients who received radiotherapy. The association between Raf1 expression and clinicopathological variables was also analyzed. The multivariate Cox proportional hazard model was used to determine the prognostic value of Raf1 in regards to progression and 3‑year survival. Significant associations between Raf1 expression and invasion and metastasis capability in lung cancer A549 and H1299 cell lines were identified. Results showed that 44.5% (49/110) of the NSCLC patient specimens demonstrated Raf1 expression, which was found to be positively correlated with lymph node metastasis (P=0.014), Tstage (P=0.038) and poor histological differentiation (P=0.029). Later progression was observed in patients with negative or low Raf1 expression than in patients with high Raf1 expression (P=0.002). The multivariate analysis indicated that Raf1 is an independent prognostic factor for time to progression (TTP) (HR,1.94; 95%CI, 1.16‑3.25; P=0.01). A high Raf1 expression was found to result in a poor 3‑year overall survival(OS)(HR,1.64; 95%CI, 0.98‑2.75; P=0.06). Raf1 overexpression was correlated with early progression in NSCLC. Raf1 may serve as a novel prognostic factor and potential target for improving the long‑term outcome of NSCLC patients.

Is BMI a risk factor for active surveillance progression in patients with prostate cancer diagnosed by MRI-Trus fusion biopsy?

124 Background: MRI−TRUS fusion biopsy (FBx) use in the diagnosis of prostate cancer (PCa) results in a more accurate assessment of disease burden and has increasingly been incorporated into urologic practice. In addition, with more men choosing active surveillance (AS) and the reports of increased PCa aggressiveness with obesity, we wanted to study the impact of obesity on the risk of PCa progression in men on AS diagnosed and followed by MRI and MRI−TRUS FBx. Methods: A retrospective review was performed on a prospectively maintained database of all men who underwent MRI−TRUS FBx at our institution from January 2007 to May 2015. Patient demographics, clinical data, imaging, pathology, treatment and outcomes were recorded. Patients who enrolled on AS were stratified by BMI into normal weight (BMI 18.5−24.9), overweight (BMI 25.0−29.9), and obese (BMI ≥ 30.0). Statistical analysis was performed using SPSS software. Results: 204 men were enrolled in AS. Within the AS cohort, 51 (25%) had a normal weight, 101 (49.5%) were overweight, and 52 (25.5%) were obese. Age, BMI, PSA and mean estimated progression free survival time are described for each of these groups in Table 1. The overall rate of progression was 32.8%. Of the patients who progressed, 18 (26.9%) were normal weight, 32 (15.7%) were overweight and 17 (25.4%) were obese. On multivariate analysis, BMI was not a risk factor for AS progression, HR = 1.00 (p = 0.99, 95% CI = 0.95−1.06). Conclusions: There is evidence of increased risk of aggressive PCa specific death in obese patients. However, we demonstrate that in patients diagnosed by FBx, obesity does not confer an additional risk of progression on AS. This may be due to the improved characterization of cancer volume and grade by MRI−TRUS fusion biopsy. Further study is required to determine risk factors for AS progression in patients undergoing FBx. This research was supported by the Intramural Research Program of the National Cancer Institute, NIH, Medical Research Scholars Program.

Depth of Invasion Alone is Not an Independent Prognostic Factor in Early-Stage Node-Negative Oral Cavity Carcinoma

The use of depth of invasion (DOI) as a prognostic factor and criterion for neck dissection (ND) in patients with oral cavity carcinoma (OCC) has been the topic of multiple clinical analyses. However, these studies are heterogeneous, frequently including patients of any stage and with multiple other histologic risk factors for recurrence. In addition, patients often received adjuvant treatment in the form of chemotherapy and/or radiation. Thus, it is difficult to draw conclusions on the importance of DOI as a true prognostic factor. We created a unique population of patients with DOI as the sole risk factor for recurrence to accurately evaluate whether it is an independent prognostic factor for progression in patients with early-stage node-negative OCC. All patients were drawn from an institutional review-board approved database of OCC patients treated at a single academic institution between 2003 and 2013. A total of 560 patients were retrospectively reviewed. Patients were included in the final analysis if they had pathologic T1-2N0 OCC treated with surgical resection with or without neck dissection (ND). Pathology specimens were independently reviewed by 2 board-certified pathologists to confirm proper evaluation of DOI and other histologic parameters. Patients were excluded if they received adjuvant treatment, chemotherapy for other cancer diagnoses in the follow up period, or if other high-risk pathologic features were present, including: perineural invasion, lymphovascular invasion, positive lymph nodes, and close or positive margins. Kaplan-Meier and Cox proportional hazards regression analyses were performed to identify factors predictive for local (LR) and regional recurrence (RR), as well as progression free survival (PFS). A total of 126 patients with T1-2 N0 OCC were analyzed. Median follow up for the entire cohort was 42.5 months and median overall survival (OS) was 46 months. Median DOI for all sites was 4 mm, with 60 (47.6%) patients with DOI <4 mm and 66 (52.4%) patients with DOI ≥4 mm. There was no significant difference in local (p=0.95), regional (p=0.81), or distant (p=0.96) recurrence between patients with DOI <4 mm and ≥4 mm. In total, 50 (42.9%) patients underwent ND. There was no significant difference in LR among patients with DOI <4 mm and ≥4 mm (p=0.95). In patients with DOI <4 mm, 5-year RR was 0% if ND was performed and 22% if ND was omitted. In the subset of patients with oral tongue carcinoma and DOI <4mm (n=36), there were no regional or distant recurrences in those patients who underwent ND compared to 20% and 4% in patients who did not undergo ND. On multivariate analysis including T stage, gender, age, DOI, and multiple head and neck primaries, the only factor significant for PFS was ND (HR 0.25, p=0.006). In this study, we show that DOI ≥4 mm alone does not predict for worse local, regional, or distant recurrence. ND appeared to improve the RR for even those with DOI <4mm.

Clinical Outcomes and Prognostic Factors of Up-Front Autologous Stem Cell Transplantation in Patients with Extranodal Natural Killer/T Cell Lymphoma

Limited data exist on up-front autologous stem cell transplantation (ASCT) in extranodal natural killer/T cell lymphoma (ENKTL). Sixty-two patients (43 men and 19 women) with newly diagnosed ENKTL who underwent up-front ASCT after primary therapy were identified. Poor-risk characteristics included advanced stage (50%), high-intermediate to high-risk International Prognostic Index (25.8%), and group 3 to 4 of NK/T Cell Lymphoma Prognostic Index (NKPI, 67.7%). Pretransplant responses included complete remission in 61.3% and partial remission in 38.7% of patients, and final post-transplantation response included complete remission in 78.3%. Early progression occurred in 12.9%. At a median follow-up of 43.3 months (range, 3.7 to 114.6), 3-year progression-free survival (PFS) was 52.4% and 3-year overall survival (OS) was 60.0%. Patients with limited disease had significantly better 3-year PFS (64.5% versus 40.1%, P = .017) and OS (67.6% versus 52.3%, P = .048) than those with advanced disease. Multivariate analysis showed NKPI and pretransplant response were independent prognostic factors influencing survival, particularly NKPI in limited disease and pretransplant response in advanced disease. Radiotherapy was an independent factor for reduced progression and survival in patients with limited disease, but anthracycline-based chemotherapy was a poor prognostic factor for progression in patients with advanced disease. Up-front ASCT is an active treatment in ENKTL patients responding to primary therapy.