Lower 5-year Overall Survival Research Articles

Time to Local Recurrence as a Predictor of Survival in Patients With Soft Tissue Sarcoma of the Extremity and Abdominothoracic Wall.

ObjectiveThe purpose of this retrospective study was to identify the prognostic significance of time to local recurrence (TLR) with regard to overall survival (OS) and survival after local recurrence (SAR) in patients with soft tissue sarcoma (STS) of the extremity and abdominothoracic wall.MethodsWe identified 477 patients who underwent R0 resection for localized STS of the extremity and abdominothoracic wall, from January 1995 to December 2016, of whom 190 patients developed local recurrence as their first recurrent event. Based on TLR, patients were divided into two groups: early local recurrence (ELR, <12 months) and late local recurrence (LLR, ≥12 months). The Kaplan–Meier method and Cox regression analysis were used to estimate the OS and SAR, and to identify factors associated with patient outcomes.ResultsThe median follow-up time for the entire cohort was 118.4 months, and was 118.5 months for the 190 patients who developed local recurrence. Deep tumor location (HR 1.73, 95% CI 1.27–2.37, P = 0.001) and tumor grade ≥2 (G2 vs. G1: HR 1.75, 95% CI 1.21–2.53, G3 vs. G1: HR 2.57, 95% CI 1.66–3.98, P < 0.001) were associated with a higher rate of local recurrence. There were 99 patients in the ELR group and 91 in the LLR group, with a median TLR of 10.8 months for the entire cohort. Patients from the ELR group had a shorter OS and a lower 5-year OS rate than the LLR group. Univariate and multivariate analyses demonstrated TLR as an independent prognostic factor for SAR and OS, in addition to tumor grade. Also, surgical treatment and absence of metastasis after local recurrence were associated with longer SAR.ConclusionsIn patients with STS of the extremity and abdominothoracic wall, ELR after R0 resection indicated a worse prognosis than those with LLR, and TLR can be considered an independent prognostic factor for OS and SAR. Furthermore, local recurrence was significantly influenced by the depth and the histopathological grading of the primary tumor, and reoperation after local recurrence could improve survival, which means salvage surgery may still be the preferred treatment when there are surgical indications after recurrence.

Validating and Refining the 8th Edition TNM N-Classification for HPV Negative Oropharyngeal Cancer

The 8th edition TNM (TNM-8) re-introduced “overt clinical extranodal extension (cENE)” as an N-classification (cN) modifier for HPV-negative (HPV–) oropharyngeal cancer (OPC), although independent validation of outcome prediction over TNM-7 is not yet available. Emerging data shows that radiologic ENE (rENE) has a high specificity to predict pathological ENE (pENE) with similar prognostic importance. This study evaluates the performance of the TNM-8 vs TNM-7 N-classifications and explores the potential role of rENE in future cN classification. All HPV– OPC patients (n = 361) treated with definitive IMRT between 2005-2016 were included. cENE was retrospectively ascertained based on unambiguous “fixation” of neck mass or “skin involvement” detected by clinical examination. Pre-treatment CT/MR of cN+ cases were reviewed by a head-neck radiologist (EY) to determine rENE, defined as unequivocal evidence of tumor invading beyond the nodal capsule. Disease-free survival (DFS) and overall survival (OS) were compared between cENE-positive (cENE+) vs cENE-negative (cENE–) and rENE-positive (rENE+) vs rENE-negative (rENE–) patients. The prognostic value of cENE and rENE was confirmed by multivariable analyses (MVA). A refined cN-classification incorporating both cENE and rENE parameters was developed and then included in a revised TNM proposal. The performance of the revision was next compared to TNM-8 and TNM-7 using established criteria examining hazard consistency within each stage, hazard distinctiveness across stages, prognostic importance of the stage schema and sample size balance. A total of 48 cENE+ and 72 rENE+ cases were identified. Of cENE+ cases, 42 were rENE+ and 6 were rENE– due to excessive time lapse between CT and clinical evaluation, or subjectivity including primary tumor misinterpretation as nodal disease. The cENE+ and rENE+ proportion increased with higher N-category (N1/N2/N3: 2%/14%/87% and 7%/23%/100%, respectively p < 0.001). Median follow-up was 5.4 years. Compared to cENE–, cENE+ patients had lower 5-year OS (25% vs 42%, p = 0.006) and DFS (17% vs 37%, p < 0.001). Compared to rENE–, rENE+ patients had lower 5-year OS (30% vs 42%, p = 0.037) and DFS (36% vs 24%, p = 0.015). MVA confirmed a prognostic impact of cENE for OS (HR = 2.3, p = 0.001) and DFS (HR = 2.8, p < 0.001). We propose a refined N-categorization that reclassifies any cENE– case with rENE+ to one N stratum higher while any cENE+ still occupies the most adverse cN3b category. The revised stage schema with the refined N-categorization, that included both cENE and rENE elements, outperformed TNM-8 and both outperformed TNM-7 in OS prediction. We confirm the prognostic value of cENE and rENE. TNM-8 N-classification with the inclusion of cENE has improved outcome prediction compared to TNM-7 in HPV-negative OPC. rENE incorporation into TNM-8 appears to additionally augment the existing N classification to facilitate clinical trial design and decision making.

Prediction of tumor recurrence by α-fetoprotein model after curative resection for hepatocellular carcinoma

BackgroundPreoperative α-fetoprotein (AFP) level levels may help select patients with hepatocellular carcinoma (HCC) for surgery. The objective of the current study was to assess an AFP model to predict tumor recurrence and patient survival after curative resection for HCC. MethodsPatients undergoing curative-intent resection for HCC between 2000 and 2017 were identified from a multi-institutional database. AFP score was calculated based on the last evaluation before surgery. Probabilities of tumor recurrence and overall survival (OS) were compared according to an AFP model. ResultsA total of 825 patients were included. An optimal cut-off AFP score of 2 was identified with an AFP score ≥3 versus ≤2 independently predicting tumor recurrence and OS. Net reclassification improvements indicated the AFP model was superior to the Barcelona Clinic Liver Cancer (BCLC) system to predict recurrence (p < 0.001). Among patients with BCLC B–C, AFP score ≤2 identified a subgroup of patients with AFP levels of ≤100 ng/mL with a low 5-year recurrence risk (≤2 45.2% vs. ≥3 61.8%, p = 0.046) and favorable 5-year OS (≤2 54.5% vs. ≥3 39.4%, p = 0.035). In contrast, among patients within BCLC 0-A, AFP score ≥3 identified a subgroup of patients with AFP values > 1000 ng/mL with a high 5-year recurrence (≥3 47.9% vs. ≤2% 38.4%, p = 0.046) and worse 5-year OS (≥3 47.8% vs. ≤2 65.9%, p < 0.001). In addition, the AFP score independently correlated with vascular invasion, tumor differentiation and capsule invasion. ConclusionsThe AFP model was more accurate than the BCLC system to identify which HCC patients may benefit the most from surgical resection.

Tobacco exposure as a major modifier of oncologic outcomes in human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma

BackgroundThe incidence of oropharyngeal squamous cell carcinoma (OPSCC) in the US is rapidly increasing, driven largely by the epidemic of human papillomavirus (HPV)-mediated OPSCC. Although survival for patients with HPV mediated OPSCC (HPV+ OPSCC) is generally better than that of patients with non-virally mediated OPSCC, this effect is not uniform. We hypothesized that tobacco exposure remains a critical modifier of survival for HPV+ OPSCC patients.MethodsWe conducted a retrospective analysis of 611 OPSCC patients with concordant p16 and HPV testing treated at a single institute (2002–2013). Survival analysis was performed using Kaplan-Meier analysis and Cox regression. Recursive partitioning analysis (RPA) was used to define tobacco exposure associated with survival (p < 0.05).ResultsTobacco exposure impacted overall survival (OS) for HPV+ patients on univariate and multivariate analysis (p = 0.002, p = 0.003 respectively). RPA identified 30 pack-years (PY) as a threshold at which survival became significantly worse in HPV+ patients. OS and disease-free survival (DFS) for HPV+ > 30 PY patients didn’t differ significantly from HPV- patients (p = 0.72, p = 0.27, respectively). HPV+ > 30 PY patients had substantially lower 5-year OS when compared to their ≤30 PYs counterparts: 78.4% vs 91.6%; p = 0.03, 76% vs 88.3%; p = 0.07, and 52.3% vs 74%; p = 0.05, for stages I, II, and III (AJCC 8th Edition Manual), respectively.ConclusionsTobacco exposure can eliminate the survival benefit associated with HPV+ status in OPSCC patients. Until this effect can be clearly quantified using prospective datasets, de-escalation of treatment for HPV + OPSCC smokers should be avoided.

Quantifying the Interplay Between Smoking and Human Papillomavirus in Risk Stratification of Patients with Oropharyngeal Cancer Undergoing Radiotherapy

The incidence of oropharyngeal squamous cell carcinoma (OPSCC) in the US is rapidly increasing, driven largely by the epidemic of human papillomavirus (HPV)-mediated OPSCC. (Gillison M, et al. J Natl Cancer Inst. 2008) Although survival for patients with HPV mediated OPSCC (HPV+ OPSCC) is generally better than that of patients with non-viral mediated (HPV-) OPSCC, the improvement is not uniform. (Vadwa N, et al. Int J Radiat Oncol Biol Phys. 2019) We hypothesized that tobacco exposure remains a critical modifier of survival for HPV+ OPSCC patients. We sought to integrate smoking into current staging system after statistically identifying a threshold value for smoking pack-years (PY) that is associated with worse survival. We also aimed at modeling the differential competing risks of treatment failure and death in HPV+ heavy and non-heavy smokers. We performed a retrospective review of patients with OPSCC treated at a single institute (2002-2013). Survival analysis was performed using Kaplan-Meier analysis and Cox regression. Recursive partitioning analysis (RPA) was used to statistically define tobacco exposure associated with survival (p<0.05). We identified 611 OPSCC patients with concordant p16 and HPV testing results. Eighty-nine percent of patients were HPV+; 50% of whom were non-smokers compared to only 20% of HPV- patients. Tobacco exposure impacted overall survival (OS) for HPV+ patients on univariate and multivariate analysis (p=0.002, p=0.003 respectively). RPA identified 30 PY as a threshold at which survival became significantly worse in HPV+ patients. OS and disease-free survival (DFS) for HPV+ >30 PY patients didn’t differ significantly from HPV- group (p= 0.72, p= 0.27, respectively). HPV+ >30 PY patients had substantially lower 5-year OS when compared to their ≤30 PYs counterparts: 78.4% vs 91.6%; p= 0.03, 76% vs 88.3%; p= 0.07, and 52.3% vs 74%; p= 0.05, for stages I, II, and III (AJCC 8th Edition Manual), respectively. A competing risk analysis of modes of failure and causes of death showed a higher risk of loco-regional failure and non-cancer deaths among HPV+ >30 PY patients compared to HPV+ ≤30 PY patients. Tobacco exposure beyond 30 PY can eliminate the survival benefit associated with HPV+ status in OPSCC patients. Until this effect can be clearly quantified using prospective datasets, de-escalation of treatment for HPV+OPSCC smokers should be avoided.

&lt;p&gt;miR-210 is a Serological Biomarker for Predicting Recurrence and Prognosis of Colon Carcinoma Patients with Liver Metastases After Radiofrequency Ablation Treatment&lt;/p&gt;

PurposeHepatic metastasis of colon carcinoma seriously affects the prognosis of patients, and miRNA has attracted much attention in predicting hepatic metastasis of colon carcinoma (CC). This research aimed to explore the predictive role of miR-210 in serum for recurrence and prognosis of CC patients with hepatic metastasis.MethodsAltogether, 150 patients with liver metastases of CC (research group, RG) and 130 patients with non-metastatic of CC (control group, CG) admitted to People’s Hospital of Deyang City from March 2012 to March 2015 were obtained and their serum was collected. miR-210 in the RG and the CG, and miR-210 in the RG after radiofrequency ablation treatment were detected, the relationship between miR-210 and pathological parameters of CC patients with hepatic metastasis was analyzed, and patients in the RG were followed up for 5 years to analyze the recurrence, overall survival (OS) and disease-free survival (DFS). The area under the curve (AUC) of receiver operating characteristic curve (ROC) was applied to test the predictive value of miR-210. Cox regression was applied to analyze the independent prognostic factors of patients.ResultsmiR-210 in the RG was evidently higher than that in the CG, and AUC for distinguishing hepatic metastasis of CC was 0.907. miR-210 had a close correlation with lymph node metastasis, distant metastasis and pathological differentiation. After treatment, miR-210 in the RG was evidently reduced, and the serum was higher in patients with recurrence and with poor prognosis. AUC for predicting recurrence was 0.858, and AUC for predicting poor prognosis was 0.843. High miR-210 was closely related to lower 5-year OS and DFS and is also an independent prognostic factor affecting patients’ 5-year OS.ConclusionmiR-210 is enhanced in hepatic metastasis of CC, which is a serological biomarker for predicting recurrence and prognosis of patients with hepatic metastasis of CC after radiofrequency ablation, and has great clinical application value.

Hazard Ratio Analysis of Laparoscopic Radical Hysterectomy for IA1 With LVSI-IIA2 Cervical Cancer: Identifying the Possible Contraindications of Laparoscopic Surgery for Cervical Cancer.

Objectives: This study aimed to compare the 5-year disease-free survival (DFS) and overall survival (OS) of laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) for IA1 with lymphovascular space invasion (LVSI)-IIA2 cervical cancer and to analyze the Cox proportional hazard ratio (HR) of LRH among the total study population and different subgroups.Methods: This was a multicenter retrospective cohort study. The oncological outcomes of LRH (n = 4,236) and ARH (n = 9,177) were compared. The HRs and 95% confidence intervals for the effect of LRH on 5-year OS and DFS were estimated by Cox proportional hazards models.Results: Overall, there was no difference in DFS between LRH and ARH in the unadjusted analysis (HR 1.11, 95% CI: 0.99–1.25, p = 0.075). The risk-adjusted analysis revealed that LRH was independently associated with inferior DFS (HR 1.25, 95% CI: 1.11–1.40, p < 0.001). There was no difference in OS between the two groups in the unadjusted analysis (HR 1.00, 95% CI: 0.85–1.17, p = 0.997) or risk-adjusted analysis (HR 1.15, 95% CI: 0.98–1.35, p = 0.091). For patients with FIGO stage IB1 and tumor size <2 cm, LRH was not associated with lower DFS or OS (p = 0.637 or p = 0.107, respectively) in risk-adjusted analysis. For patients with FIGO stage IB1 and tumor size ≥2 cm, LRH was associated with lower 5-year DFS (HR 1.42, 95% CI: 1.19–1.69, p < 0.001) in risk-adjusted analysis, but it was not associated with lower 5-year OS (p = 0.107). For patients with FIGO stage IIA1 and tumor size <2 cm, LRH was not associated with lower 5-year DFS or OS (p = 0.954 or p = 0.873, respectively) in risk-adjusted analysis. For patients with FIGO stage IIA1 and tumor size ≥2 cm, LRH was associated with lower DFS (HR 1.48, 95% CI: 1.16–1.90, p = 0.002) and 5-year OS (HR 1.69, 95% CI: 1.22–2.33, p = 0.002) in risk-adjusted analysis.Conclusion: The 5-year DFS of LRH was worse than that of ARH for FIGO stage IA1 with LVSI-IIA2. LRH is not an appropriate option for FIGO stage IB1 or IIA1 and tumor size ≥ 2 cm compared with ARH.

Can neoadjuvant chemotherapy improve survival in stage T3-4N1 nasopharyngeal carcinoma? A propensity matched analysis

BackgroundTo estimate the efficacy of neoadjuvant chemotherapy (NCT) in stage T3-4N1 nasopharyngeal carcinoma (NPC).MethodsData on stage T3-4N1 NPC patients treated with concurrent chemoradiotherapy (CCRT) with or without NCT at the Sun Yat-sen University Cancer Center between January 2006 and December 2013 were retrospectively reviewed. Propensity score matching (PSM) was carried out to balance prognostic factors in NCT followed by CCRT (NCT + CCRT) group and CCRT group in a 1:1 ratio. Survival outcomes of matched patients in the two groups were compared, and prognostic factors were identified using Cox regression model.ResultsA total of 282 patients were involved in this study, with 136 of NCT + CCRT group and 146 of CCRT group. After PSM, 85 pairs of patients were selected. There were no significant differences in 5-year overall survival (OS), locoregional recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), and recurrence-free survival (RFS) between NCT + CCRT group and CCRT group (81.0% vs. 77.5%, P = 0.750; 85.8% vs. 88.1%, P = 0.495; 92.5% vs. 93.9%, P = 0.759; 81.0% vs.77.5%, P = 0.919, respectively). Multivariate analysis found that smoking history (P = 0.044) and T classification (P = 0.027) were independent prognostic factors for OS, lymph node diameter (P = 0.032) was independent prognostic factor for LRFS, positive pretreatment lymph node condition (PLNC), which was defined as the lymph node necrosis or confluent, was independent prognostic factor for DRFS (P = 0.007), and RFS (P = 0.009). Lower 5-year OS (82.7% vs. 94.1%, P = 0.014), DRFS (79.3% vs. 96.2%, P = 0.003), and RFS (62.4% vs. 86.8%, P = 0.001) were found in positive PLNC group compared with negative PLNC group. In terms of toxicities, the incidences of acute hematological Grade 3–4 adverse events (AEs) were higher in NCT + CCRT group compared with CCRT group (P < 0.05), while no significant difference was observed in the rates of non-hematological Grade 3–4 AEs between these two groups (P > 0.05).ConclusionsAdditional NCT is not associated with improved survival outcomes for patients with stage T3-4N1 NPC, but bring increased hematological Grade 3–4 AEs. PLNC is independent prognostic factor in stage T3-4N1 NPC, with positive PLNC correlating with poor survival outcomes.

Long non-coding RNA PVT1-mediated miR-543/SERPINI1 axis plays a key role in the regulatory mechanism of ovarian cancer.

Purpose: To investigate the regulation mechanism of long non-coding RNA (lncRNA) plasmocytoma variant translocation 1 (PVT1) in ovarian cancer (OC).Methods: The levels of PVT1, microRNA (miR)-543, serpin peptidase inhibitor-clade I (neuroserpin)-member 1 (SERPINI1) in OC tissues and OVCAR-3, A2780, TOV-112D of OC cell lines were detected by quantitative real-time PCR (qRT-PCR) and Western Blot (WB). Cell proliferation, migration, invasion, apoptosis and the regulatory relationship between genes and target genes were analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Transwell, flow cytometry and dual luciferase reporter (DLR). The OC patients were followed up for 5 years to analyze the relationship between PVT1 and 5-year overall survival (OS).Results: In contrast with miR-543, PVT1 and SERPINI1 were highly expressed in OC tissues and cell lines, and high levels of PVT1 were significantly associated with lower 5-year OS of patients. Down-regulating PVT1 not only inhibited the malignant proliferation, migration and invasion of OC cells, but promoted cell apoptosis. PVT1 regulated miR-543 in a targeted manner, and its overexpression could attenuate the anticancer effect of miR-543 on OC cells. In addition, miR-543 also directly targeted SERPINI1, and miR-543 knockdown weakened the inhibitory effect of down-regulated SERPINI1 on OC progression. Furthermore, we found that PVT1 acted as a competitive endogenous RNA to sponge miR-543, thereby regulating the expression of SERPINI1.Conclusion: PVT1 can mediate the molecular mechanism of OC by miR-543/SERPINI1 axis regulatory network, which is a new therapeutic direction for OC.

Evaluation of factors associated with the risk stratification of survivorship for stage IV squamous cell carcinoma of the oral cavity: A 10-year retrospective study.

Oral squamous cell carcinoma (OSCC) leads to thousands of deaths every year in Taiwan. Nearly 40% of OSCC patients are diagnosed with stage IV disease, which has a poor prognosis. Multimodality treatments including surgery and adjuvant therapy have been utilized, but their treatment outcomes are generally poor. In this study, we sought to identify possible clinical impact factors that may contribute to the survival of stage IV OSCC. Data for patients with malignant neoplasms of the oral cavity registered in the Cancer Registry Database of Taipei Veterans General Hospital between 2002 and 2011 were retrieved. The study patients consisted of OSCC patients with clinical stage IV disease who had undergone a surgery and adjuvant therapy. The primary endpoints were the 5-year disease-free survival (DFS) and overall survival (OS) rates. The clinicopathological characteristics of the patients were also stratified and compared. A total of 191 OSCC patients were included for retrospective analysis. The different subgroups of stage IV disease presented different treatment outcomes. The 5-year OS versus DFS rates of each subgroup were as follows: T4N0: 70.9% versus 52.6%; T1-3N23: 66.1% versus 49.8%; T4N1: 49.6% versus 31.6%; and T4N23: 40.9% versus 31.0% (p < 0.01). Patients with diabetes, moderate or poor cell differentiation, perineural invasion, and extracapsular spread presented lower 5-year OS rates (hazard ratio [HR] = 1.87, 1.65, 2.42, and 2.14, respectively), and patients with perineural invasion, positive cut margin, and extracapsular spread presented lower 5-year DFS rates (HR = 1.57, 1.62, and 1.71, respectively). In this study, we elucidated the different survival rates of different subgroups of stage IV OSCC following the same treatment scheme. The results of the study provide clinical physicians with references by which to evaluate prognosis and determine post-operative disease monitoring timetables based upon different characteristics.

The Prognostic Role of Pretransplant Serum Lactate Dehydrogenase Levels in Acute Myeloid Leukemia and Lymphoma Patients Undergoing Allogenic Hematopoietic Stem Cell Transplantation

<h3>Background</h3> Risk stratification is a critical step when considering allogeneic hematopoietic stem cell transplantation (HSCT). While Lactate dehydrogenase (LDH) is a readily available biomarker with a prognostic role in the front-line therapy setting of hematological malignancies, its' role in the pretransplantation setting is undefined. <h3>Methods</h3> This was a retrospective study on a cohort of patients who underwent allogeneic-HSCT at a single center between 2000 and 2016. Pre transplant LDH levels and other clinical features were extracted from medical record. The primary outcome was overall survival (OS), and secondary outcomes included non-relapse mortality (NRM) and relapse (considered as competing events). The median follow-up time was 59 months (IOR 27 - 112). We analyzed the association between median LDH levels, per disease category. Associations meeting a p-value below 0.05 for the primary outcome were further explored in a multivariable Cox regression (cause-specific Cox for competing events). The model was adjusted for age, disease risk index (DRI), year of HSCT, donor type, and conditioning regimens. <h3>Results</h3> A total of 1,250 adult (median age 52.8 years) patients with the following disease were included; Acute myeloid leukemia (AML, n=594; 48%), non-Hodgkin lymphoma (NHL, 211, 16.9%), acute lymphoblastic leukemia (ALL, n=175, 14%), myelodysplastic syndrome (n=165, 13%), and plasma cell dyscrasia (PCD, n=105, 8%). In the univariate analysis, AML patients with higher than median LDH levels (>193 IU/L) had lower 3-year OS (51.9% vs. 39.2%, p<0.001) (Fig.1A), and higher cumulative incidence of NRM (15.7% vs. 19.6%, p<0.04), and relapse incidence (RI) (26.7% vs. 40.7%, p<.0001). In a cubic spline (Fig.1B), we showed that the relationship between increasing LDH and reduced OS was linear (p<0.001). Higher LDH maintained its prognostic capacity in the multivariable Cox model (OS: hazard ratio [HR] 1.34 95% CI [1.06-1.7], NRM: [HR] 1.31 95% CI [0.87-1.98], RI: [HR] 1.42 95% CI [1.07-1.89]). In a univariate analysis of NHL patients, LDH levels above median value (>228 IU/L) was associated decreased OS (51.9% vs. 39.2%, p<.0001) (Fig.1C), and increased RI (17.1% vs. 29.2%., p=0.02), but not NRM. Using a cubic spline (Fig.1D), the association between LDH and mortality was also linear (p=0.007). Other malignancies did not reach statistical significance. <h3>Conclusion</h3> Using a systematic approach, we showed that pre-transplantation LDH is a potent biomarker that could be used for risk stratification for AML and NHL patients who are candidates for allogeneic-HSCT. While further validation is warranted it may be rewarding to incorporate LDH in future prognostic models assessing the risk of transplantation.

Impact of HHV-6 in Recipients of Ex Vivo T-Cell Depleted Hematopoietic Cell Transplant

<h3>Introduction</h3> Recipients of ex-vivo T-cell depleted (TCD) (CD34⁺ selected) hematopoietic cell transplant (HCT) are at increased risk for infections by double-stranded DNA viruses. TCD HCT recipients at Memorial Sloan Kettering Cancer Center were routinely screened for HHV-6 by plasma PCR between 2012 and 2016. The objectives of our study were to 1) report the incidence of persistent HHV-6 viremia and disease 2) identify risk factors of persistent HHV-6 viremia; 3) examine the association between persistent HHV-6 viremia and overall survival (OS) at 1-year post-HCT. <h3>Methods</h3> Recipients with TCD HCT between 2012 and 2016 routinely screened for HHV-6 by plasma PCR were reviewed retrospectively. CD34⁺ selection was performed by the CliniMACS CD34 Reagent system (Miltenyi Biotec, Germany). HHV-6 viremia was defined as ≥1 HHV-6 viral load (VL) >limit of quantification. Persistent HHV-6 viremia was defined as ≥2 consecutive measurements of VL ≥500 copies/mL through day+100 post-HCT, death, relapse, and second transplant whichever occurred first. Cox proportional model was used to examine the risk factors of persistent HHV-6 viremia. One-year OS was estimated by Kaplan-Meier method. <h3>Results</h3> Of 312 patients, 59% were male and median age was 55 years (range, 22-73). 67% had acute leukemia and myelodysplastic syndrome and 18% had mismatched donors. 55% developed HHV-6 viremia. Eighty-three (27%) had persistent HHV-6 viremia with a median duration of 67 days (interquartile range [IQR], 56-75) (Figure 1). Mismatched donor (P=0.04) and recipient CMV seronegativity (R-) (P=0.04) were associated with persistent HHV-6 viremia. Of 83 patients with persistent HHV6 viremia, 23 (28%) had max VL ≥10,000 copies/mL and 7 (8%) developed HHV-6 disease (encephalitis 1, pneumonitis 4, and organizing pneumonia 2). Maximum VL with HHV-6 disease was a median VL 71,700 copies/mL (IQR, 8,211-123,500). Persistent HHV-6 viremia was associated with lower absolute lymphocyte counts (ALCs) up to 1-year post-HCT (figure 2) and lower 1-year OS (P=0.02) (figure 3). <h3>Conclusion</h3> 27% of TCD HCT recipients developed persistent HHV-6 viremia. Mismatched donor and CMV R- were associated with persistent HHV-6 viremia. Among patients with persistent HHV-6 viremia, 8% developed HHV-6 disease. Persistent HHV-6 viremia was associated with lower ALCs and OS at 1-year post-HCT.

Correlation analysis between CXC chemokine receptor 6 and prognosis of renal clear cell carcinoma

Objective To investigate the correlation between CXC chemokine receptor 6 (CXCR6) and prognosis of renal clear cell carcinoma. Methods A total of 100 patients with renal clear cell carcinoma who underwent surgery in the First People's Hospital of Ziyang from January 2013 to October 2014 were selected. Immunohistochemistry was used to detect the expression of CXCR6 in 100 cases of renal clear cell carcinoma and adjacent normal tissues. The patients were followed up to observe the positive rate of CXCR6 expression and the factors affecting overall survival (OS) and progression-free survival (PFS) of renal clear cell carcinoma and adjacent normal tissues. Results The positive rate of CXCR6 expression in renal clear cell carcinoma tissues was higher than that in adjacent tissues, and the difference was statistically significant [46.0% (46/100) vs. 20.0% (20/100), χ2 = 15.287, P < 0.01]. The positive expression rate of CXCR6 in patients with clinical stage Ⅲ-Ⅳ, lymph node metastasis and pathological grade Ⅲ-Ⅳ was higher than that in patients with clinical stage Ⅰ- Ⅱ, pathological grade Ⅰ- Ⅱ and without lymph node metastasis, and the difference was statistically significant (all P < 0.05). A total of 92 patients were followed up and 40 died. The follow-up time reached to (35-60) months and the median follow-up time was 48.9 months. Kaplan-Meier and log-rank test showed that patients with positive CXCR6 expression had lower 3-year OS and PFS rate compared with patients with negative CXCR6 expression, and the difference was statistically significant (3-year OS rate: 52.1% vs. 78.6%, χ2 = 10.027, P = 0.001; 3-year PFS rate: 48.3% vs. 67.8%, χ2 = 4.344, P = 0.037). Cox regression multivariate analysis showed pathological grade (OS: OR = 2.154, 95% CI 1.547-9.517, P = 0.023; PFS: OR = 1.235, 95% CI 1.109-5.917, P = 0.042), lymph node metastasis (OS: OR = 1.412, 95% CI 1.109-5.917, P = 0.041; PFS: OR = 1.841, 95% CI 1.354-8.994, P = 0.010), CXCR6 expression (OS: OR = 1.864, 95% CI 1.358-6.813, P = 0.031; PFS: OR = 1.457, 95% CI 1.127-6.884,P = 0.025) were independent risk factors of OS and PFS for renal clear cell carcinoma patients treated by the surgery. Conclusions The positive expression of CXCR6 is an independent risk factor for OS and PFS of renal clear cell carcinoma. The prognosis of patients with positive CXCR6 expression is poor. Key words: Carcinoma, renal cell; Receptors, chemokine; Prognosis

Overexpression of B7H5/CD28H is associated with worse survival in human gastric cancer.

Gastric cancer (GC) is a common malignancy with low 5‐year overall survival (OS). Recently, immune therapy has been used to treat cancer. B7H5 and CD28H are novel immune checkpoint molecules. However, the prognostic value of B7H5/CD28H expression in patients with GC remains unclear. In this study, seventy‐one patients diagnosed with GC were included in this study. Patients' GC tissues and matched adjacent tissue constructed a tissue microarray. The expression levels of B7H5 and CD28H were examined using immunohistochemistry. Correlations between the expression of B7H5 and CD28H and the clinical data were evaluated. We found that the expression of B7H5 and CD28H (both P = .001) were higher in GC tumour tissues than in adjacent noncancerous tissues. B7H5/CD28H expression acted as an independent predictive factor in the OS of patients with GC. High expression of B7H5 and CD28H predicted poor outcome. Patients in the B7H5+CD28H+ group had a lower 5‐year OS compared with patients in the B7H5−CD28− group (4.5% vs 55.6%, P = .001). A significant difference was found in the 5‐year OS between patients in the B7H5+CD28H− and B7H5+CD28H+ groups (33.5% vs 4.5%, P = .006). However, there was no correlation between B7H5 and CD28H expression (P = .844). Therefore, B7H5 and CD28H expression are up‐regulated in GC and are independent prognostic factors for overall survival in patients with GC. Although there was no correlation between B7H5 and CD28H expression, high expression of B7H5 and CD28H predicts poor prognosis, especially when both are highly expressed.

Association of Body Composition with Long-Term Survival in Non-metastatic Rectal Cancer Patients.

PurposeWe evaluated the association of body composition with long-term oncologic outcomes in non-metastatic rectal cancer patients.MethodsWe included 1,384 patients with stage(y)0-III rectal cancer treated at Asan Medical Center between January 2005 and December 2012. Body composition at diagnosis was measured using abdomino-pelvic computed tomography (CT). Sarcopenia, visceral obesity (VO), and sarcopenic obesity (SO) were defined using CT measured parameters such as skeletal muscle index (total abdominal muscle area, TAMA), visceral fat area (VFA), and VFA/TAMA. Inflammatory status was defined as a neutrophil-lymphocyte ratio of ≥3. Obesity was categorized by body mass index (≥ 25 kg/m2).ResultsAmong the 1,384 patients, 944 (68.2%) had sarcopenia and 307 (22.2%) had SO. The 5-year overall survival (OS) rate was significantly lower in sarcopenic patients (no sarcopenia vs. sarcopenia; 84% vs. 78%, p=0.003) but the 5-year recurrence-free survival (RFS) rate was not different (77.3% vs. 77.9% p=0.957). Patients with SO showed lower 5-year OS (79.1% vs. 75.5% p=0.02) but no difference in 5-year RFS (p=0.957). Sarcopenia, SO, VO, and obesity were not associated with RFS. However, obesity, SO, age, sex, inflammatory status, and tumor stage were confirmed as independent factors associated with OS on multivariate analysis. In subgroup analysis, association of SO with OS was more prominent in patients with (y)p stage 0-2 and no inflammatory status.ConclusionThe presence of SO and a low body mass index at diagnosis are negatively associated with OS in non-metastatic rectal cancer patients.

Survival After Abdominal Q-M Type B versus C2 Radical Hysterectomy for Early-Stage Cervical Cancer.

PurposeTo evaluate the survival outcomes of abdominal Q-M type B and type C2 radical hysterectomy (RH) for early-stage (IA1 (lymphovascular invasion)-IIA2) cervical cancer.Patients and methodsBased on this multicenter, retrospective cohort study on the clinical diagnosis and treatment for cervical cancer in China (Four C), the survival outcomes of abdominal type B and type C2 RH for early-stage cervical cancer were compared under real-world and matched cohort study conditions.ResultsIn total, 46,313 cases were included in the Four C database, among whom 20,018 underwent abdominal type B or type C2 RH. In the real-world study, no differences were found in the 5-year overall survival (OS) between the type B group (n=15,471) and type C2 group (n=4547), but the 5-year disease-free survival (DFS) was lower in the type C2 group (82.1 vs 84.8%, hazard ratio: 1.144). Based on the inclusion criteria, 9135 cases were included and the type C2 group (n=1818) was found to have a lower 5-year OS and DFS (OS: 89.5 vs 92.0%, hazard ratio: 1.393; DFS: 84.3 vs 87.4%, hazard ratio: 1.342). Subsequently, 1799 cases from each group were matched and the type C2 group had a lower 5-year DFS (84.6 vs 88.4%, hazard ratio: 1.332). Upon further analysis of the subgroups, the type C2 group had a lower 5-year OS and DFS (OS: 90.3 vs 93.8%, hazard ratio: 1.522; DFS: 85.2 vs 89.4%, hazard ratio: 1.439).ConclusionQ-M type B RH could be used for the treatment of stage IA1 (lymphovascular invasion)-IIA2 cervical cancer.

Patterns and Prognostic Value of Lymph Node Metastasis on Distant Metastasis and Survival in Nasopharyngeal Carcinoma: A Surveillance, Epidemiology, and End Results Study, 2006-2015.

This study was conducted to identify factors associated with lymph node (LN) metastasis in nasopharyngeal carcinoma (NPC) patients, analyze node distribution patterns, and explore the prognostic value of the LN metastasis level for survival. We included 2994 patients with primary NPC diagnosed between 2006 and 2015 with information in the Surveillance, Epidemiology, and End Results (SEER) database. Patients' demographic and clinicopathologic features were compared according to LN status using chi-squared tests. The 5-year overall survival (OS) and cancer-specific survival (CSS) rates were calculated by the Kaplan–Meier method, and the differences were estimated by log-rank tests. Multivariate Cox proportional hazard models were used to evaluate independent risk factors for OS and CSS. Logistic regression was used to evaluate the risk of each LN metastasis category for distant metastasis. There were 695 patients in the N0 stage and 2299 with LN metastasis (classified as stage N1, N2, or N3). The overall incidence of LN metastasis was 76.8%. Sex and T stage were not associated with LN metastasis. Older patients had a significantly worse 5-year OS and CSS than younger patients. In terms of histologic type, keratinizing squamous cell carcinoma had the lowest 5-year OS and CSS at 48.2% and 53.8%, respectively. The most common nodal involvement level was II (65.9%), followed by III (29.1%), V (25.6%), I (17.6%), IV (15.7%), and retropharynx (13.5%). The skip metastasis rate was 5.7% (130/2299). Patients with only level II metastasis (classified as level 2) was the most common category, accounting for 30%. Compared to level 2, patients with only level I (classified as level 1) had an OR of 2.101 (95% CI: 1.090–4.047, P=0.027) for distant metastasis, patients with simultaneous levels II, III, IV, and V (classified as levels 2345) had the highest OR of 4.064 (95% CI: 2.155–7.666, P < 0.001) for distant metastasis, and level 24 had an OR of 3.003 (95% CI: 1.074–8.395, P=0.036) for distant metastasis. In survival analysis, levels 235 had a significant HR of 1.708 (95% CI: 1.089–2.678, P=0.020) for CSS compared to level 2 after adjustment for age, sex, race, histology, TNM (tumor, node, and metastasis) stage, and treatment.

The Comparison of Hypomethylating Agents (HMA) Monotherapy with HMA Combined with Intensive Chemotherapy for Intermediate / High-Risk MDS or AML

Introduction: Hypomethylating agents (HMA) azacitidine and decitabine were the first-line therapy for intermediate/ higher-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients unsuitable for hematopoietic cell transplantation (HSCT). HMA combined with chemotherapy was recently used to achieve for a better outcome. However, few studies were carried out to compare the HMA monotherapy to the HMA and chemotherapy combination therapy. This meta-analysis aimed to compare the efficacy, survival benefit and safety of HMA monotherapy and combination therapy (with chemotherapy) in patients with intermediate/high-risk MDS or AML. Methods: Related articles published between January 2009 and April 2019 were selected and patients were separated as monotherapy group and combination group for meta-analysis. To further eliminate the potential influence of differences in patients' baseline characteristic between the two groups, subgroups with similar patients' baseline characteristics were selected for further analysis. Complete response (CR) rate, overall response (ORR) rate, 1-year overall survival (OS) rate, 1-month death rate and the proportion of adverse event (AE) were pooled and compared. Results: 13 RCT or cohort studies with 997 patients (790 in monotherapy group, 207 in HMA combination group) were selected for meta-analysis. For the pooled data, there was no significant difference in sex and cytogenetic risk between the 2 groups, but the age of combination therapy group was significantly younger than that of the monotherapy group (61.3±13.2 year-old vs 67.7±10.2 year-old, p=0.000). The CR and ORR rate were significantly higher in combination therapy group (53% vs 17%, p=0.000 for CR and 67% vs 44%, p=0.000 for ORR). However, the 1-year OS (56% for combination therapy vs 51% for HMA monotherapy group, p=0.282) and 1-month death rate (5% for combination therapy vs 4% for HMA monotherapy group, p=0.965) were similar between the two groups. The incidence of CTCAE grade 3-4 infection and bleeding were significantly higher (infection: 50% for combination therapy vs 25.7% for monotherapy group, p=0.003; bleeding: 27.5%% for combination therapy vs 7.8% for monotherapy group, p=0.004) in combination group. In subgroup analysis, 117 and 179 patients were included in combination group and HMA monotherapy group, respectively. There was no significant difference in age (69.5±4.6 vs 69.0±6.8 years old, p=0.451) and proportion of favorable/intermediate cytogenetic risk (62% vs 71%, p=0.114) between the two groups, but a significantly lower proportion of male was found in combination therapy group (57% vs 74%, p=0.003). Although combination group had a higher CR rate (49% vs 17%, p=0.000), it had similar ORR rate (58% vs 49%, p=0.140) to monotherapy group. Meanwhile, combination therapy came with higher 1-month death rate (12% vs 3%, p=0.008) and lower 1-year OS (54% vs 68%, p=0.013) compared with monotherapy group. Conclusions: HMA combined with chemotherapy could increase CR rate in all patients and ORR rate in younger patients, but could not improve OS. For patients with similar older age, combination therapy could result in higher 1-month death rate and less 1-year OS. Disclosures No relevant conflicts of interest to declare.

Lactate Dehydrogenase Is a Key Prognostic Factor in Acute Myeloid Leukemia and Lymphoma Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Background: Risk stratification is critical for balancing the potential benefit and harm of allogeneic hematopoietic stem cell transplantation (HSCT). However, our ability to do so is suboptimal and better markers are warranted. Lactate dehydrogenase (LDH) is a readily available biomarker with a well-established prognostic role in the front-line therapy setting of hematological malignancies. Few reports in selected diseases have studied the utility of LDH as a surrogate for pre-transplant risk-stratification. We, therefore, sought to systematically study the prognostic role of LDH in patients with various hematological malignancies undergoing allogeneic - HSCT. Methods : This was a retrospective study on a cohort of patients who underwent allogeneic-HSCT at a single center between 2000 and 2016. LDH levels in the day before conditioning initiation were extracted from the electronic medical record, as well as features related to patients, disease, donor, and transplant. The primary outcome was overall survival (OS), and secondary outcomes included non-relapse mortality (NRM) and relapse (considered as competing events). The median follow-up time was 59 months (IOR 27 - 112). Using Kaplan-Meier estimates or cumulative incidence curves for competing events, we analyzed the association between median LDH levels, per disease category, with the detailed outcomes. Associations meeting a p-value below 0.05 for the primary outcome were further explored in a multivariable Cox regression (cause-specific Cox for competing events). The model was adjusted for age, disease risk index (DRI), year of HSCT, donor type, and conditioning regimens. Results A total of 1,250 adult (median age 52.8 years) patients were included in this study. Acute myeloid leukemia (AML) was the leading transplantation induction (n=594; 48%), followed by non-Hodgkin lymphoma (NHL, 211, 16.9%), acute lymphoblastic leukemia (ALL, n=175, 14%), myelodysplastic syndrome (MDS, n=165, 13%), and plasma cell dyscrasia (PCD, n=105, 8%). The majority of patients had intermediate-risk disease (44%), sibling or match unrelated donor (51% and 31% respectively) and received myeloablative or reduced-toxicity conditioning regimens (27% and 36%, respectively). In the univariate analysis, AML patients with higher than median LDH levels (&gt;193 IU/L) had lower 3-year OS (51.9% vs. 39.2%, p&lt;0.001) (Fig.1A), and higher cumulative incidence of NRM (15.7% vs. 19.6%, p&lt;0.04), and relapse incidence (RI) (26.7% vs. 40.7%, p&lt;.0001). We constructed a cubic spline (Fig.1B), which showed that the relationship between increasing LDH and reduced OS was linear (p&lt;0.001). Higher LDH maintained its prognostic capacity in the multivariable Cox model (OS: hazard ratio [HR] 1.34 95% CI[1.06-1.7], RI :[HR] 1.42 95% CI[1.07-1.89]) though not in NRM: [HR] 1.31 95% CI [0.87-1.98] .In a univariate analysis of NHL patients, LDH levels above median value (&gt;228 IU/L) was associated decreased OS (51.9% vs. 39.2%, p&lt;.0001) (Fig.1C), and increased RI (17.1% vs. 29.2%., p=0.02), but not NRM. Using a cubic spline (Fig.1D), we showed that the association between LDH and mortality is also linear (p=0.007). LDH did not meet the criteria for statistical significance for all studied outcomes in ALL, MDS, and PCD. Conclusion Using a systematic approach, we show that pre-transplantation LDH is a potent biomarker that could be used for risk stratification for AML and NHL patients who are candidates for allogeneic-HSCT. While further validation is warranted it may be rewarding to incorporate LDH in future prognostic models assessing the risk of transplantation. Figure 1 Disclosures No relevant conflicts of interest to declare.

An Analysis from the WM UK Rory Morrison Registry - How Does Waldenström's Macroglobulinemia Affect Younger Patients?

Introduction Waldenström's macroglobulinaemia (WM), an indolent IgM-secreting non-Hodgkin's B-cell lymphoplasmacytic lymphoma, has a reported average age of diagnosis of 65-70 years. and it is often regarded as a disease of the elderly. However, a significant proportion of patients are diagnosed at a younger age and data about this cohort is relatively limited, partly because of the low disease incidence. We seek to further elucidate the characteristics and impact of the disease in the younger patient cohort. Methods The WMUK Rory Morrison Registry (RMR) was searched for all patients younger than 60 years on day of diagnosis. Demographics, disease characteristics, treatment information and survival status were collected retrospectively. Results of patient reported outcome measures (PROMs) were collated. Results 269 patients from 16 UK centres were identified, with years of diagnosis between 1978 and 2018. Analysis focused on 235 patients who fulfilled diagnostic criteria for WM. Patient characteristics are shown in table 1. M:F ratio was 1.61:1 of which 158 patients were Caucasian, 17 Asian, 5 Black, 3 mixed and 6 of other ethnicity, 56 unrecorded. Bone marrow results were available in 156 patients from time of diagnosis, with a median infiltration of 40%. MYD88 L265P was found in 61/74 patients (82.4%) and CXCR4 mutation in 14/39 patients (35.9%). Median Hb was 114/L (range 33-170), platelet count 250x109/L (range 24-689), IgM 19 (range 0-65) and B2-microglobulin 2.7mcg/mL (range 0.5-56.3). The baseline IPSSWM scores were available for 115 patients. 9 patients were anti-MAG antibody positive and 11 had cryoglobulins. Treatment was received by 164 patients (69.8%). The median time from diagnosis to treatment was 2.5 months, range 0-312 months; 69 patients had one line, 32 two lines, 31 three lines, 12 four lines, and 20 five or more lines.14% received R-CHOP as first line therapy, 12.2% DRC,12.2% R-Bendamustine, 7.3% Rituximab monotherapy, 6.7% R-CVP and 6.7% chlorambucil. However, since 2010 DRC and R-Bendamustine were the most frequent. Following first line treatment, 14.7% achieved CR, 55.3% PR or VGPR, 11.9% MR and 14% had SD or PD. At some point in their disease course, high-grade transformation (HGT) was noted in 2 patients and CNS involvement in 10. 30 patients had undergone autologous and six patients allogenic transplantation. Complete, up to date survival information was available for 188 patients, of who 40 patients were deceased (median time from diagnosis 116 months, range 14-451 months). Unfortunately, cause of death was available for only 8 patients at time of analysis, including disease-related in 4, sepsis in 2, HGT in 1 and subdural haemorrhage in 1. One-, 5- and 10-year overall survival (OS) rates were 99.5%, 90% and 81.1%. There was a significant difference in OS according to IPSSWM risk (log rank, P &amp;lt;0.005), with a 5-year OS rate of 92.% for the low risk, 79% for the intermediate, and 38% for the high risk group. There was no significant difference in OS rates according to age group. Of 164 patients asked about their level of disease understanding on a scale of 0-10, the median rating was 0 (average rating 1.85). Only eight patients rated it as 10. Functional information was available for 62 patients, of who 42 (67.7%) had impairment in their ability to go for a walk outside, eight patients (12.9%) required assistance with self-care and one patient (1.6%) was fully dependent on others for personal care. 32 patients (51.6%) needed to spend some or most of their day in a bed or chair. 29 patients (47.8%) had suffered significant financial difficulties because of their diagnosis. Of 59 patients who responded about psychological wellbeing, 36 patients (61%) described feeling depressed. One patient described feeling 'very' depressed, 8 patients 'moderately' depressed and 27 patients 'slightly' depressed. Conclusion A significant proportion of patients with WM are diagnosed under the age of 60 years, and despite its limitations, this retrospective analysis of a large cohort of younger patients illustrates the evolving treatment landscape in the UK. To be expected, WM significant impacts on quality of life and psychological and financial wellbeing in a cohort who would expect to be in work. Encouragingly, OS rates are generally good, although a high IPSSWM risk carries a markedly lower 5-year OS rate also in the younger cohort. A more detailed analysis is underway to explore these issues further. Disclosures McCarthy: Janssen: Honoraria, Other: Educational grant to attend meetings . Pratt:Binding Site, Amgen, Takeda, Janssen, Gilead: Consultancy, Honoraria, Other: Travel support. D'Sa:Janssen: Honoraria, Research Funding.