Predictor Of Worse Overall Survival Research Articles

Socio-demographic determinants of myelofibrosis outcomes in an underserved center and the SEER national database.

The influence of demographic characteristics and social determinants on cancer outcomes is widely recognized in various malignancies but remains understudied in myelofibrosis (MF). This study aims to investigate social and demographic variables associated with MF survival. We retrospectively reviewed data of biopsy-proven MF patients from the Surveillance, Epidemiology and End Results (SEER) database (2000-2021) and Montefiore Medical Center (2000-2023), an underserved inner-city hospital. The SEER cohort included 5,403 MF patients and was predominantly Non-Hispanic (NH) White (82%) with a median age of 69 years. The age-adjusted incidence rate of MF was 0.32 cases per 100,000 person-years, increasing annually by 1.3% from 2000 to 2021. Two- and five- year overall survival rates were 69% and 42%, respectively. Worse cause-specific survival was associated with older age, male sex, and diagnosis before 2011 (year of Ruxolitinib approval). NH-Black ethnicity, unmarried status and lower median income were independent predictors of worse overall survival. The single-center analysis included 84 cases, with a median age of 66 years. NH-White patients comprised 37% of the sample, followed by NH-Black (28.5%). Two- and five- year overall survival rates were 90% and 61%, respectively, with NH-Black patients exhibiting the lowest median survival, although the difference was not statistically significant. Age was a significant predictor of worse survival in this cohort. NH-Black and Hispanic patients lived in areas with higher socioeconomic and demographic stress compared to NH-White patients. Overall, this study highlights the association of social and demographic factors with MF survival and emphasizes the need for equitable healthcare and further exploration of social-demographic factors affecting MF survival.

Survival of patients with lymph node versusbone versus visceral metastases according to CHAARTED/LATITUDE criteria in the era of intensified combination therapies for metastatic hormone-sensitive prostate cancer.

The first approvals of novel systemic therapies within recent years for metastatic hormone-sensitive (mHSPC) were mainly based on improved overall survival (OS) and time to castration resistance (ttCRPC) in mHSPC patients stratified according to CHAARTED low (LV) versus high volume (HV) and LATITUDE low (LR) versus high-risk (HR) disease. Relying on our institutional tertiary-care database we identified all mHSPC stratified according to CHAARTED LV versus HV, LATITUDE LR versus HR and the location of the metastatic spread (lymph nodes (M1a) versus bone (M1b) versus visceral/others (M1c) metastases. OS and ttCRPC analyses, as well as Cox regression models were performed according to different metastatic categories. Of 451 mHSPC, 14% versus 27% versus 48% versus 12% were classified as M1a LV versus M1b LV versus M1b HV versus M1c HV with significant differences in median OS: 95 versus 64 versus 50 versus 46 months (p < 0.001). In multivariable Cox regression models HV M1b (Hazard Ratio: 2.4, p = 0.03) and HV M1c (Hazard Ratio: 3.3, p < 0.01) harbored significant worse than M1a LV mHSPC. After stratification according to LATITUDE criteria, also significant differences between M1a LR versus M1b LR versus M1b HR versus M1c HR mHSPC patients were observed (p < 0.01) with M1b HR (Hazard Ratio: 2.7, p = 0.03) and M1c HR (Hazard Ratio: 3.5, p < 0.01), as predictor for worse OS. In comparison between HV M1b and HV M1c, as well as HR M1b versus HR M1c no differences in ttCRPC or OS were observed. Significant differences exist between different metastatic patterns of HV and LV and HR and LR criteria. Best prognosis is observed within M1a LV and LR mHSPC patients.

Impact of perioperative high-protein nutritional support on postoperative outcomes in the treatment of primary lung cancer: Russian prospective multicenter comparative study (NUTRILUNC-study)

BACKGROUND: Up to 60% of lung cancer pts experience weight loss. Prevalence of sarcopenia in patients (pts) with non-small cell lung cancer (NSCLC) is about 43% and is an independent predictor of worse overall survival. It was shown that nutritional support improves outcomes in pts with cancer. AIM: To evaluate impact of perioperative nutritional support on surgical treatment outcomes of patients with NSCLC. MATERIALS AND METHODS: Patients with primary NSCLC (n=112, 69 males), aged 57,2±8,2, awaiting lung surgery and being at risk of malnutrition (Nutritional Risk Screening Assessment 2002 score ≥3) were randomized into 2 groups. Study group (n=55) received oral nutritional support (Nutridrink Compact Protein, Nutricia LLC), 250 ml/d (36 g of protein, 612 kcal) for 14 d before and 14 d after surgery in addition to standard diet. Control group (n=57) had a standard diet. The number of respiratory complications after surgery, length of hospitalization, anthropometric, functional, laboratory parameters, quality of life (according to Quality of Life Questionnaire Core-30) were assessed. Results were presented as mean ± standard deviation. Differences were considered significant at p ≤0.05. RESULTS: In the study group there were fewer respiratory complications (p 0.01), and a shorter length of hospitalization (p=0.03). Body weight in the study group did not change significantly, while in the control group it decreased (0.15±3.7 kg versus loss of 3.47±3.6 kg). Results of six-minute walk test and hand grip dynamometry were higher in the study group then in the control group (411.8±56.0 m versus 383.2±52.1 m; 33.5±8.4 kg versus 27.1±6.8 kg). Quality of life was better in the study group, p 0.05. The total protein and albumin levels were higher in the study group (70.9±5.6 g/l versus 63.1±4.0 g/l; 38.5±5.8 g/l versus 33.2±3.0 g/l). One patient in study group experienced 1st grade diarrhea. CONCLUSION: In patients with NSCLC at risk of malnutrition perioperative nutritional support with high protein oral nutritional support has a positive effect on surgical treatment outcomes.

Melanocortin-1 Receptor Expression as a Marker of Progression in Melanoma.

Melanocortin-1 receptor (MC1R) plays a critical role in human pigmentation and DNA repair mechanisms. MC1R-targeting agents are being investigated in clinical trials in patients with melanoma, yet large studies investigating the rate and degree of MC1R expression in primary and metastatic human melanoma tissue are lacking. Using tissue microarrays containing three large cohorts of 225 cases of benign nevi, 189 with primary melanoma, and 271 with metastatic melanoma, we applied quantitative immunofluorescence and immunohistochemistry to comprehensively study MC1R protein expression. We show a stepwise elevation of MC1R expression in different stages of melanoma progression (nevi, primary, metastasis). Higher MC1R expression was seen in deeper (>1 mm) primary lesions and ulcerated lesions and was associated with shorter survival in primary and metastatic tumors. On multivariable analysis, Breslow thickness, male sex, and chronic sun exposure were independent predictors of worse overall survival in the primary melanoma cohort. Our data suggest that MC1R might be a valuable drug target in aggressive melanoma. Additional studies are warranted to determine its functional significance in melanoma progression and its utility as a predictive biomarker in patients receiving MC1R-directed therapies.

Association of iron overload with infectious complications in liver transplant recipients: a systematic review and meta-analysis.

This study was performed to examine the possible association of iron overload with infectious complications and survival among liver transplant recipients. We conducted a systematic review and meta-analysis of studies published in the PubMed, Embase, Web of Science, and Cochrane Library databases up to September 2022. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted to estimate the association of iron overload with infectious outcomes and overall survival after liver transplantation. Eight studies involving 2817 recipients met the inclusion criteria. Iron overload was strongly associated with an increased risk of infection after liver transplantation (HR, 1.66; 95% CI, 1.03-2.68). An increase in the serum ferritin level was associated with an increased risk of infection after liver transplantation (HR, 1.44; 95% CI, 1.09-1.91). Iron overload was a significant predictor of worse overall survival (HR, 1.35; 95% CI, 1.11-1.64). In addition, a high serum ferritin level was significantly associated with an increased risk of death (HR, 1.34; 95% CI, 1.10-1.64). Iron overload may be associated with a higher risk of infectious complications and a worse prognosis among liver transplant recipients.

Evaluation of Absolute Neutrophil Count in the Perioperative Setting of Sarcoma Resection.

Limb salvage surgery (LSS) is the preferred surgical treatment for bone sarcomas. Preoperatively, many patients receive chemotherapy and may develop neutropenia. No study has evaluated the effect of a low preoperative absolute neutrophil count (ANC) on postoperative outcomes following LSS. This was a retrospective review of 114 patients who underwent LSS for bone sarcoma from 2010 to 2020. Preoperative lab values were analyzed by logistic regression to identify the risk of developing surgical complications within 30 days, surgical site infection (SSI), and reoperation. Three (2.6%) patients experienced a surgical complication within 30 days. Twelve (10.53%) patients experienced postoperative SSI. Twenty-nine (25.4%) required reoperation. Preoperative ANC was not a significant predictor of surgical complications within 30 days, SSI, or reoperation. The only independent predictor of worse overall survival was the presence of a pathologic fracture at the time of surgery. This is the first study to evaluate preoperative ANC on postoperative outcomes following LSS. We report no significant differences in surgical complications within 30 days, SSI, or reoperation with low preoperative ANC. Future studies with larger cohorts of neutropenic patients are needed to evaluate these outcomes, as our cohort had very few neutropenic patients due to selection bias.

The effect of hormonal secretion on survival in adrenocortical carcinoma: A multi-center study

BackgroundCurrent evidence suggests that cortisol secreting adrenocortical carcinoma has worse prognosis compared to non-secreting adrenocortical carcinoma. However, the effect of other secretory subtypes is unknown. MethodsThis multicenter study within the American-Australian-Asian Adrenal Alliance included adults with adrenocortical carcinoma (1997–2020). We compared overall survival and disease-free survival among cortisol secreting, mixed cortisol/androgen secreting, androgen secreting, and non-secreting adrenocortical carcinoma. ResultsOf the 807 patients (mean age 50), 719 included in the secretory subtype analysis: 24.5% were cortisol secreting, 13% androgen secreting, 28% mixed cortisol/androgen, 32.5% non-secreting, and 2% were mineralocorticoid secreting.Median overall survival and disease-free survival for the entire cohort were 60 and 9 months, respectively. Median overall survival was 36 months for cortisol, 30 for mixed, 60 for androgen secreting, and 115 for non-secreting adrenocortical carcinoma, P < .01. Median disease-free survival was 7 months for cortisol, 8 for mixed, 10 for androgen, and 12 for non-secreting adrenocortical carcinoma, P = .06.On multivariable analysis of age, sex, Ki67%, secretory subtype, stage, resection, and adjuvant therapy, predictors of worse overall survival were older age, higher Ki67%, stage IV, mixed secreting, R1, and no adjuvant therapy, P < .05. On subgroup analysis of R0 resection, predictors of worse overall survival included older age and higher Ki67%. Ki67% ≥40, stage III and cortisol secretion were associated with worse disease-free survival. ConclusionMixed cortisol/androgen secreting adrenocortical carcinoma was associated with worse overall survival, while cortisol or androgen secreting alone were not. Notably, among patients after R0 resection, secretory subtype did not affect overall survival. Cortisol secreting adrenocortical carcinoma demonstrated worse disease-free survival. Ki67% remained a strong predictor of worse overall survival and disease-free survival independent of stage.

Proper position of single and large (≥5 cm) hepatocellular carcinoma in Barcelona Clinic Liver Cancer classification.

The purpose of this study was to evaluate the proper position of single large hepatocellular carcinoma (HCC) in the Barcelona Clinic Liver Cancer (BCLC) staging system. The data were collected from the nationwide multicentre database of the Korean Liver Cancer Association. Patients with single large (≥5 cm) HCC were separated from BCLC stage A patients and designated as Group X. The remaining BCLC stage A and stage B patients were classified as Group A and Group B, respectively. The survival outcomes of propensity score-matched groups were compared. Among the 3965 randomly selected patients, the number of patients in Group X, Group A, and Group B was 414, 2787, and 760, respectively. TriMatch analysis allowed us to obtain 116 well-balanced triplets. The 1-, 3-, and 5-year overall survival rates in Group X were worse than in Group A (91%, 71%, and 48% vs 90%, 78%, and 64%, respectively; P < .000). However, the rates were not different compared with those in Group B (91%, 71%, and 48% vs 90%, 69%, and 48%, respectively; P < .09). In multivariate analysis, Group X, Group B, age over 60 years, prothrombin time-international normalized ratio, and creatinine level were independent predictors of worse overall survival. Our findings suggest that Group X should be relocated to BCLC stage B rather than BCLC stage A.

Prognostic Impact of Mismatch Repair Deficiency on Stage I-II Endometrioid Endometrial Cancer Treated with Adjuvant Radiation Therapy: A Multi-Institutional Analysis

To report the impact of mismatch repair (MMR) status on outcomes in patients with stage I-II endometrioid endometrial cancer (EEC). This is a multi-institutional retrospective cohort study across 11 institutions. Preliminary data from 7 centers is available for analysis. Patients with known MMR status and stage I-II EEC status post-surgical staging treated with adjuvant radiation therapy were included. Overall survival (OS) and recurrence-free survival (RFS) rates were estimated by the Kaplan-Meier method. Univariate and multivariate analyses were performed by Cox proportional hazard models for OS/RFS. Statistical analyses were conducted using statistical software. A total of 573 patients with median age at diagnosis of 65 years (Interquartile Range (IQR) 58-71) were eligible. Most patients were White (79%), had FIGO 2009 Stage I (89.7%) and FIGO grade 1-2 (74.7%). MMR deficiency (dMMR) was reported in 191 patients (33%) while 382 patients (67%) had preserved MMR (pMMR). External beam radiation therapy (EBRT) +/- vaginal brachytherapy (VBT) was delivered to 124 patients (21.6%) while 449 patients (78.4%) received VBT alone. After a median follow-up of 41 months ((IQR) 28-60 months), the estimated OS and RFS rates for the entire cohort were 95.1% and 85%, respectively. On univariate analysis, age >65 (p < 0.001), grade 3 (p < 0.001), presence of lymphovascular space invasion (LVSI) (p = 0.039) and deep myometrial invasion (p = 0.03) were associated with worse OS. The OS was inferior in the dMMR group, however, it did not reach significance (92% vs 96.1%, p = 0.06). On multivariate analysis, older age (p < 0.001) and grade 3 (p = 0.002) were the only predictors for worse OS. On univariate analysis for RFS, age >65 (p = 0.02), grade 3 (p = 0.018) and dMMR (72.9% vs 91%, p < 0.001) were associated with worse RFS. On multivariate analysis, age >65 (p = 0.015) and dMMR (p < 0.001) were significant predictors of worse RFS. Preliminary data from 7 out of 11 participating institutions showed that dMMR status leads to significantly decreased RFS in patients with early-stage EEC. While awaiting the results of NRG GYN020 and RAINBO prospective trials, this large study suggests that treatment intensification could be warranted in patients with dMMR early-stage EEC.

Small Bowel Neuroendocrine Tumors-10-Year Experience of the Ottawa Hospital (TOH).

(1) Aim: The prevalence and incidence of small bowel NETs have increased significantly over the past two decades. This study aims to report the 10-year experience of SB-NET management at a regional cancer center in Canada. (2) Materials and methods: We conducted a retrospective study of the clinical and pathological data of patients diagnosed with biopsy-proven SB-NET at The Ottawa Hospital (TOH), Ottawa, Canada between 2011 and 2021. We report the clinicopathological characteristics of these patients, as well as their outcomes data, including survival rates. (3) Results: Between 2011 and 2021, a total of 177 SB-NET cases were identified with 51% (n = 91) of cases being males. The most common sites of the tumors were the ileum 53% (n = 94), followed by the duodenum 9% (n = 16) and jejunum 7% (n = 12). Approximately 24% (n = 42) of the patients had symptoms for over six months prior to diagnosis and 18% (n = 32) had functioning SB-NET during the course of the disease. The majority of patients had locally advanced or metastatic disease at the time of presentation with stage III, and stage IV representing 42% (n = 75), and 41% (n = 73) respectively. The majority of patients 84% (n = 148) had well-differentiated histology. One hundred twenty patients underwent surgical resection of the primary tumor including 28 patients (16%) with limited metastatic disease. A total of 21 patients (18%) had recurrence after curative surgery. A total of 62 patients (35%) received first-line somatostatin analog (SSA) therapy for unresectable disease and seven patients had PRRT after progression on SSA. Five years OS was 100%, 91%, 97%, and 73% for stages I, II, III, and IV respectively. In univariate analysis, carcinoid symptoms, T stage, and differentiation were significant predictors for worse overall survival, but not RFS. (4) Conclusions: Compared to published historical controls, our study suggests improvement in the 5-year survival rate of SB-NETs over the last 10 years.

Prognostic impact of primary tumor sidedness in stage III colorectal cancer.

e15622 Background: Primary tumor sidedness (PTS) has been shown to be an independent prognostic factor for patients with metastatic colorectal cancer (CRC), with worse prognosis for right-sided tumors. There are limited data regarding the prognostic impact of PTS in stage III CRC. Objective: The main objective of this study was to analyze the prognostic impact of PTS in stage III CRC. Methods: A retrospective and uni-institutional cohort study was performed in a reference center in São Paulo-SP, Brazil. All consecutive patients with stage III CRC and treated with a 5-fluorouracil and oxaliplatin-based chemotherapy regimen (mFLOX regimen) from October 2007 to February 2013 were included. The primary outcome was probability of overall survival (OS) at 5 years stratified by PTS. Secondary outcomes were probability of disease-free survival (DFS) at 5 years stratified by PTS, and analysis of the prognostic impact of clinical and molecular biomarkers. The time-to-event variables were reported by the Kaplan Meier estimation method and prognostic factors associated with OS and DFS were assessed by Cox models. Results: 265 patients were included. Transverse colon tumors, multicentric tumors and undetermined primary subsite were later excluded, totaling 234 patients who were classified according to PTS: 95 on the right side (40.6%) and 139 on the left side (59.4%). Median age was 58 and 59 years for right- and left-sided tumors, respectively. For both groups, approximately 67% had stage IIIB. The median follow-up time was 66 months (range: 0-149). The 5-year OS probabilities for right-sided and left-sided tumors were 67% (95% CI: 58%-77%) and 82% (75%-89%), respectively. [Hazard ratio [HR]=2.02, 95% CI: 1.18–3.46; p=0.010). The 5-year probability of DFS for right-sided and left-sided tumors were 58% (49%-69%) and 65% (58%-74%), respectively. [HR=1.29, 0.84-1.97; p=0.248). Of the 234 patients, 61 patients (26%) had tissue samples available for DNA sequencing by NGS and immunohistochemical analysis. Of these, 12 patients (19.7%) had a RAS mutation, no patient had a BRAF mutation (V600E) and 6 patients (9.8%) had DNA repair enzyme deficiency (dMMR). No statistically significant difference was identified in the probability of OS and DFS at 5 years when comparing patients with right-sided and left-sided tumors when stratified by RAS mutation status and MMR status. Among patients with right-sided tumors, age &gt;70 years (HR=4.11, 1.67-10.1; p=0.002), pN2 (HR=2.52, 1.23-5.17; p=0.012) and high-risk stage III according to the IDEA trial (HR=2.95, 1.35-6.44; p=0.002) were predictors of worse OS at 5 years. Among patients with left-sided tumors, poorly differentiated histology (HR=3.93, 1.44-10.7; p=0.007) and angiolymphatic invasion (HR=5.23, 1.54-17.8; p=0.008) were predictors of worse OS in 5 years. Conclusions: Data indicate a worse prognosis (inferior OS at 5 years) for resected right-sided stage III CRC treated with adjuvant mFLOX regimen.

Treatment outcomes in adults with newly diagnosed B-cell acute lymphoblastic leukemia: A comparison between pediatric-inspired regimens and HyperCVAD at a Hispanic-serving cancer center.

7048 Background: It is unknown if HyperCVAD is more favorable than pediatric-inspired regimens (PIRs) among adult Hispanic patients with newly diagnosed B-cell acute lymphoblastic leukemia. This analysis aims to determine the interaction of Hispanic ethnicity and treatment regimen on outcomes. Methods: Records of adults (≥ 18 years) treated with a PIR or HyperCVAD from January 2011 to November 2022 at our institution were reviewed. Patients were excluded if they received treatment modifications in a clinical trial or were lost to follow-up prior to 6 months. The primary endpoint was event-free survival (EFS) comprised of relapse, death, secondary malignancy, or failure to achieve complete remission. Secondary endpoints included overall survival (OS). Ph+ disease was not grouped into the poor-risk category. Results: 100 patients were included. Median age was 39 years, 57% were male, and 61% self-identified as Hispanic. 48 were included in the PIR and 52 in the HyperCVAD groups. 37 in the PIR group received CALGB 10403. There was no difference in race, ethnicity, rituximab use, WBC, LDH, bone marrow blast %, presence of CNS disease at diagnosis, or poor-risk genetics (Table) between the PIR and HyperCVAD groups. However, a lower rate of Ph+ disease (8.3% vs 58%) and younger median age (31 years vs 49 years) was observed in the PIR group. Allogeneic stem cell transplantation (ASCT) was pursued in 48% of PIR and 37% of HyperCVAD-treated patients. EFS at 5-years was lower among patients receiving a PIR compared to HyperCVAD (28% vs 41%; hazard ratio [HR], 1.89; P = .022). After censoring for ASCT there was no change (P = .03). Treatment group was the only significant predictor for EFS although a treatment-by-subgroup interaction (P &lt; .10) with Hispanic ethnicity was found. OS at 5-years was 61% in PIR and 64% in HyperCVAD-treated patients (HR, 1.54; P = .25). In multivariable Cox regression analysis, Hispanic ethnicity (HR, 2.56; P = .041) and male sex (HR, 2.62; P = .027) were predictors for worse OS. Hispanic patients demonstrated worse EFS with a PIR compared to HyperCVAD (HR, 2.52; P = .008), which remained significant when evaluating only Ph- patients (HR, 2.20; P=.048). Non-Hispanics did not experience the same difference in EFS (HR, 0.88; P=.81). Conclusions: Treatment with a PIR resulted in worse EFS over HyperCVAD in adult Hispanic ALL patients. Future studies focusing on regimen intensity, adherence, and toxicities are needed to explore potential causes for this disparity. [Table: see text]

Prognostic value of 18F-fluorodeoxyglucose uptake in the bone marrow on pretreatment positron emission tomography/computed tomography in patients with esophageal cancer who underwent esophagectomy.

Increased 18F-fluorodeoxyglucose (FDG) uptake in the bone marrow (BM) on positron emission tomography/computed tomography (PET/CT) clinically reflects increased BM metabolism owing to systemic inflammation, bacterial infection, anemia, and cytokine-producing tumors. The association between FDG uptake in the BM and prognosis after esophagectomy for esophageal cancer has not been investigated. This study included 651 patients who underwent PET/CT before any treatment and McKeown esophagectomy for esophageal cancer between June 2007 and August 2021. The pretreatment degree of FDG uptake in the BM was evaluated using a visual assessment criterion. Patients were divided into low- and high-FDG uptake groups. We retrospectively investigated whether the degree of FDG uptake in the BM was associated with clinicopathological and surgical backgrounds, blood parameters, and prognosis. High FDG uptake in the BM was significantly associated with elevated white blood cell and neutrophil counts, increased C-reactive protein levels, decreased hemoglobin, serum albumin, and total cholesterol levels. High FDG uptake in the BM was an independent predictor of worse overall survival in clinical stages 0-II esophageal cancer (hazard ratio, 2.27; 95% confidence interval, 1.097-4.695; P = 0.027). Worse overall survival was also associated with advanced age, low American Society of Anesthesiologists physical status, an advanced clinical stage, and high intraoperative blood loss. Increased FDG uptake in the BM on pretreatment PET/CT may be a surrogate indicator of various clinically disadvantageous backgrounds and may act as a predictor of poor prognosis after esophageal cancer surgery.

MP56-07 IMPACT OF SMOKING, CUMULATIVE EXPOSURE AND CESSATION ON ONCOLOGIC OUTCOMES AFTER RADICAL CYSTECTOMY AND ADJUVANT CHEMOTHERAPY FOR LOCALLY-ADVANCED BLADDER CANCER: A MULTICENTER STUDY

MP56-07 IMPACT OF SMOKING, CUMULATIVE EXPOSURE AND CESSATION ON ONCOLOGIC OUTCOMES AFTER RADICAL CYSTECTOMY AND ADJUVANT CHEMOTHERAPY FOR LOCALLY-ADVANCED BLADDER CANCER: A MULTICENTER STUDY

Comparison of clinicopathologic features, survival, and demographics in sebaceous carcinoma patients with and without Muir-Torre syndrome

Visceral malignancies in patients with Lynch syndrome behave less aggressively than in those without Lynch syndrome. The behavior of sebaceous carcinoma (SC) in Muir-Torre syndrome (MTS), a variant of Lynch syndrome, is incompletely investigated. To investigate features and survival of SC patients with and without MTS. Retrospective cohort study in the Surveillance, Epidemiology, and End Results 17 database from 2000 to 2019 of patients with SC. Patients were classified as MTS or non-MTS cases based on a threshold score of 2 on the Mayo MTS risk score. We identified 105 (2.8%) MTS cases and 3677 (97.2%) non-MTS cases. On univariate analysis, MTS patients were younger, had a higher proportion of tumors outside the head/neck, and had fewer high-grade tumors. On Kaplan-Meier analysis, MTS patients trended toward having better SC-specific survival. On multivariate Cox proportional hazards analysis adjusting for other covariates, MTS status was an independent predictor of worse overall survival. However, there was no association between MTS status and SC-specific survival. Given relatively high disease-specific survival in SC, our study may have been underpowered to detect a difference on Kaplan-Meier analysis. Our study suggests SC does not behave more aggressively in patients with MTS.

Expression of p53 and Rb reveal subtypes of gastric neuroendocrine carcinoma with distinct prognosis.

Gastric neuroendocrine carcinoma (NEC) is a rare tumor with a poor prognosis. Due to its rarity and disparity in prevalence across populations, there is limited data on gastric NEC. TP53 and RB1 genetic alterations or expression were reported for predictive value in neuroendocrine neoplasm and classification in pulmonary large cell NEC. This study investigated the genetic alteration and protein expression of TP53 and RB1 in gastric NEC. Thirty-nine patients were categorized as type A and B subtypes by p53 and Rb expression. Patients with concurrent abnormal p53 and Rb expression were defined as the type A group, and the remainder were defined as the type B group. Significant differences in TNM stages, tumor size, and lymph node metastasis were observed between the two subtypes. Type A characteristic is an independent predictor for worse overall survival (HR: 3.27; 95% CI: 1.12-9.58; p=.022). We further evaluated and compared immunotherapy-related markers, including PD-L1 expression, CD8 T cell infiltration, tumor mutation burden, and microsatellite instability in these two subtypes, whereas no significant differences were detected.

Prognostic impact of postoperative neutrophil-to-lymphocyte ratio on survival outcomes of patients treated with radical nephroureterectomy for upper urinary tract urothelial carcinoma: a single institution retrospective analysis using propensity score matching.

Purpose: To investigate the prognostic impact of postoperative neutrophil to lymphocyte ratio (NLR) on survival outcomes in upper urinary tract urothelial carcinoma (UTUC). Materials and methods: Data from 397 patients with UTUC who underwent radical nephroureterectomy (RNU) without a history of neoadjuvant chemotherapy between 2002 and 2017 were retrospectively analyzed. Based on a postoperative NLR cut-off of 3, patients were divided into low NLR (<3) or high NLR (≥ 3) groups. After 2:1 propensity score matching, a Kaplan-Meier with log-rank test was used to compare survival outcomes between the two groups. Univariate and multivariate Cox proportional hazard models were used to investigate the impact of the postoperative NLR on survival outcomes. Results: The matched cohort (n=176) consisted of 116 low NLR and 60 high NLR patients. The Kaplan-Meier curves showed significant differences in the 3- and 5-year overall and cancer-specific survival rates between the two groups (each p = 0.03). Multivariate Cox regression analysis revealed that a postoperative high NLR was an independent predictor of worse overall survival (hazard ratio [HR]:2.13; 95% confidence interval [CI]:1.18-3.85, p = 0.012) and cancer-specific survival (HR:2.16; 95% CI 1.11-4.21, p = 0.024). Conclusions: Propensity score matching analysis revealed postoperative high NLR can be considered a potential inflammatory biomarker for predicting survival outcomes of UTUC patients treated with RNU.

HLA Evolutionary Divergence (HED) Informs the Effect of HLA-B-Loci Mismatch on Relapse and Disease Free Survival after Haploidentical Hematopoietic Cell Transplantation (Haplo) with Post-Transplant Cyclophosphamide (PTCY)

The Success of allogeneic Hematopoietic cell transplantation (HCT) is dependent on a potent graft versus tumor (GVT) benefit. GVT relies on tumor-associated antigens TAAs that are presented to donor T cells via human leukocyte antigens HLAs. The high diversity of HLAs allows for presentation of immense repertoire of peptides including TAAs. HLAs are polymorphic and each allele presents a different repertoire of peptides referred to as the immunopeptidome. The HLA evolutionary divergence (HED) between alleles of a single individual can dictate the ability to present TAAs. Patients with higher HED can present a more diverse immunopeptidome, including TAAs and potentially have a benefit of higher GVT after allogeneic HCT. The effect of HED was studied among cancer patients receiving immune check point inhibitors where high HED diversity was associated with better survival. Low recipient HEDs in HLA class I and DR were strong predictors for worse overall survival after matched donor HCT. The effect of HED divergence among recipients of haplo HCT with PTCY has not been evaluated. Moreover, the mismatch between donor and recipient in haplo HCT allows for assessing the effect of HED divergence in the donor and in the donor/recipient mismatched haplotype. To study the effect of HED among recipients of haplo HCT, we analyzed 322 consecutive recipient/donor pairs who received their transplant at our center with a median follow up of 57.2 months (range 18-196). HED was calculated as pairwise differences using two methods: a Grantham distance metric using a perl Script ( https://sourceforge.net/projects/granthamdist/) and manual calculation of one random sample from each analysis to verity results. Data were collected from our database where it was prospectively entered. Patient diagnosis included AML (n=122), ALL (n=68), MDS (n=41), NHL (n=50), other (n=41). Baseline recipient characteristics included a median age of 50 years (19,80), 53% white, HCT-CI≥3 in 50%, Disease risk (intermediate 53%, high/very high 33%), PBSC graft 80% and myeloablative conditioning 49%. Donor characteristics were median age 37 years (13,73), CMV positive 61%, male 61% and female donor to male recipient 21%. Pairwise divergence of HLA class I and class II showed differences in values with HLA-B, DRB1 and DQB1 contributing most to mean HED class I and II. The HED values for recipient included mean HLA class I 6.85 (HLA-A 7.08, B 8.24 and C 3.47), class II 8.58 (DRB1 10.97, DQB1 10.06 and DPB1 4.06). Donor mean HED HLA-class I was 6.5 (HLA-A 6.43, B7.93 and C 4.61), mean HLA-class II was 8.84 (DRB1 10.93, DQB1 11.24 and DPB1 4.06). The mean HEDs for the mismatched haplotype between donor and recipient were class I 6.49 (A 6.43, B 7.8, C4.94) and Class II 8.74 (DRB1 10.48, DQB1 10.06, DPB1 4.06). Next, we performed a univariate Cox model to identify HED variables that are associated with OS, DFS, NRM and relapse. Based on continuous and dichotomized divergence (median cutoff) univariate cox, a high HED in class I mismatched donor-recipient haplotype was significant for worse DFS (HR 1.11, p=0.020), and relapse (HR 1.11, p=0.02). Also, high HED in HLA B in mismatched haplotype was significant for worse OS (HR 1.07, p=0.02), DFS (HR 1.09, p=0.002), higher relapse (HR 1.10, p=0.003) and similar NRM to low HED. AS HLA-B was the biggest contributor to class I HED mean and the only predictor of outcomes in a univariate cox, we evaluated HLA-B in mismatched haplotype ( donor-recipient) further in a Multivariate analysis using dichotomization based on median level. Variables in the analysis included were age (<55, ≥55), gender, race, diagnosis, cell source, regimen intensity, HCT-CI (0-2, ≥3), DRI (low/intermediate, high/very high), CMV status; donor age (<38, ≥38), donor gender, female-donor-to-male-recipient, donor CMV status, year of transplant. The multivariate cox analysis showed that high HED (≥7.8 vs <7.8) was significant for worse DFS ( HR 1.53, 95% CI 1.09-2.16; p=0.01), higher relapse (HR 1.61, CI 1.07-2.44, p=0.024) and similar NRM and OS (table 1) . The significance was reproduced in the lymphoid and myeloid lineages. In Summary, among patients receiving haplo with PTCY, a high divergence in HLA-B mismatch haplotype increases relapse risk and worsens DFS. In addition to this being the first analysis to assess HED in a large haplo cohort, the negative consequences of HED can be mitigated by selecting donors with lower HED in the mismatched haplotype at HLA-B. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Recurrence Risk Stratification for Women with FIGO Stage I Uterine Endometrioid Carcinoma Who Underwent Surgical Lymph Node Evaluation

<h3>Purpose/Objective(s)</h3> To estimate the recurrence risk based on the number of prognostic factors in women with FIGO stage I uterine endometrioid carcinoma (EC) in a large cohort of patients who underwent surgical staging including surgical lymph node evaluation (SLNE) and were managed with no adjuvant therapy. <h3>Materials/Methods</h3> We queried our in-house prospectively maintained uterine cancer database for patients with FIGO stage I EC underwent surgical staging including SLNE between 1/1990-12/2020. Patients with synchronous ovarian and breast cancer diagnosis were excluded as well as those who received adjuvant therapy of any form. Patient's demographics and pathologic variables were analyzed. We used multivariate analysis (MVA) with Stepwise Model Selection to determine risk factors for 5-year recurrence-free survival (RFS). Study population was then stratified based on the number of risk factors identified (0, 1 or 2). The resultant groups were compared for RFS, disease-specific survival (DSS) and overall survival (OS) using log-rank test and Kaplan-Meier curves. Additionally, independent predictors of DSS and overall OS were estimated. <h3>Results</h3> 706 patients were identified who met our inclusion criteria with a median age of 60 years (range, 30-93) and a median follow-up of 120 months. All patients had at least pelvic SLNE with a median number of examined lymph node (LN) of 8 (range, 1-66): 66 patients (11%) had a sentinel LN sampling and 43% had paraaortic SLNE. 639 patients (91%) were stage IA and lymphovascular space invasion (LVSI) was detected in 6% (n=41). Recurrence was diagnosed in 44 patients (6%). Independent predictors of 5-year RFS include age ≥ 60 years (<i>p</i>=0.038), grade 2 vs. 1 (<i>p</i>=0.003), and grade 3 vs 1 (<i>p</i><0.001). 5-year RFS for group-0 (age < 60 years and grade 1) was 98% vs. 92% for group-1 (either: age ≥ 60 years or grade 2/3) vs 84% for group-2 (both: age ≥ 60 years and grade 2/3), respectively (<i>p</i><0.001). 5- year DSS for the three groups was (100% vs 98% vs 95%, <i>p</i>=0.012) and 5-year OS was (98% vs 90% vs 81%, <i>p</i><0.001), respectively. On MVA, stage IB vs IA was deterministic for DSS (<i>p</i>=0.02); whereas age ≥ 60 years (p<0.001) and grade 3 vs grade 1 (<i>p</i>=0.004) were predictors for worse OS. <h3>Conclusion</h3> In patients with stage I endometrioid carcinoma who had surgical staging including SLNE and no adjuvant therapy, only age ≥ 60 years and high tumor grade were independent predictors of cancer recurrence and hence can be used to quantify individualized recurrence risk. Surprisingly, LVSI was not an independent prognostic factor in this study cohort with SLNE.

Gemcitabine-Paclitaxel Chemotherapy for Patients with Advanced Urothelial Cancer Refractory to Cisplatin-Based Chemotherapy: Predictive Role of PGK1 for Treatment Response to Cytotoxic Chemotherapy.

An investigation of alternatives to immune checkpoint inhibitors for advanced urothelial cancer (aUC), with biologic information, is urgently needed. Clinical data for 53 patients who received gemcitabine–paclitaxel therapy (GP) as 2nd-line chemotherapy for aUC refractory to platinum-based chemotherapy were retrospectively reviewed. The efficacy and tolerability of GP were evaluated, and the predictive value of phosphoglycerate kinase 1 (PGK1) immunostained in surgical specimens was investigated for treatment outcomes in 1st- and 2nd-line chemotherapy. GP was associated with an objective response rate of 35.8% and a median overall survival duration of 12.3 months. Multivariate analysis showed that PS2 and 1st- and 2nd-line non-response are independent predictors of worse progression-free survival and that PS2 and 1st-line non-response are independent predictors of worse overall survival. Adverse events were manageable, and no therapy-related deaths occurred. Non-response rates to 1st-line chemotherapy were significantly higher in patients with a high expression of PGK1 in the nucleus than in those with low expression (p = 0.006). Our study demonstrates the efficacy and tolerability of 2nd-line GP for patients with aUC who are refractory to platinum-based chemotherapy. Moreover, PGK1 in the nucleus was predictive values for resistance to platinum-based chemotherapy in aUC.