5-year Cumulative Rate Research Articles

A Nomogram to Predict Recurrence After Bronchial Artery Embolization for Hemoptysis Due to Bronchiectasis.

To develop and validate a nomogram for predicting recurrent hemoptysis after successful bronchial arterial embolization (BAE) in patients with bronchiectasis. From January 2015 to December 2019, a total of 251 patients were enrolled in this study. A nomogram was developed with the predictors of recurrent events, which were identified by univariate and multivariate Cox regression analyses. We evaluated nomogram discrimination by area under the receiver operating characteristic curve, calibration by the calibration curve, and clinical usefulness potential by decision curve analysis. The one-month, 1-year, 2-year, 3-year, and 5-year cumulative recurrence-free rates of patients were 98.4%, 90.5%, 82.8%, 77.7%, and 74.4%, respectively. Three predictive factors, namely sex, lung destruction, and systemic arterial-pulmonary circulation shunts, were applied to develop the nomogram. The model maintained good discrimination (area under the curve, 0.72; 95% confidence interval, 0.62-0.81), low prediction error (integrated Brier score, 0.129), and certain net benefits in terms of clinical usefulness. The proposed nomogram showed favorable predictive efficacy for hemoptysis recurrence after BAE in patients with bronchiectasis. Improved long-term outcomes are expected with close follow-up, a healthy lifestyle, and pulmonary rehabilitation for patients at risk of recurrence according to the model.

Long-term outcomes of endoscopic balloon dilation for intestinal strictures in patients with Crohn's disease during maintenance treatment with anti-tumor necrosis factor alpha antibodies.

Efficacy of endoscopic balloon dilation (EBD) for intestinal strictures in patients with Crohn's disease (CD) receiving anti-tumor necrosis factor alpha antibodies (anti-TNF) as maintenance therapy is unclear. We investigated the long-term efficacy and safety of EBD for intestinal strictures in patients with CD receiving anti-TNF. We retrospectively analyzed data from patients with CD who received anti-TNF as maintenance therapy from 2008 to 2017, underwent EBD, and were followed up for ≥6 months. The primary endpoint was the cumulative surgery-free rate. The main secondary endpoints were technical success, repeat EBD rate, risk factors affecting surgical outcomes, and safety. Seventy-two patients with CD were assessed. The median observation period after EBD was 50 months. The technical success rate was 67%. The 3- and 5-year cumulative surgery-free rates were 81.1% and 73.5%, respectively. The repeat EBD rate was 74%. Multivariable analyses showed that risk factors affecting surgical outcomes were age at disease onset ≤16 years (hazard ratio 3.69; 95% confidence interval 1.36-10.01; P = 0.011). Serious complications requiring surgery developed in three patients. Endoscopic balloon dilation was an effective and safe short-term treatment and a useful long-term treatment for CD patients with intestinal strictures receiving anti-TNF as maintenance therapy.

Association of improved overall survival with decreased distant metastasis following asparaginase-based chemotherapy and radiotherapy for intermediate- and high-risk early-stage extranodal nasal-type NK/T-cell lymphoma: a CLCG study

BackgroundThis study evaluated the survival benefit of asparaginase (ASP)-based versus non-ASP-based chemotherapy combined with radiotherapy in a real-world cohort of patients with early-stage extranodal nasal-type natural killer/T-cell lymphoma (ENKTCL).Patients and methodsWe identified 376 patients who received combined radiotherapy with either ASP-based (ASP, platinum, and gemcitabine; n = 286) or non-ASP-based (platinum and gemcitabine; n = 90) regimens. The patients were stratified into low-, intermediate-, and high-risk groups using the early stage-adjusted nomogram-revised risk index. Overall survival (OS) and distant metastasis (DM)-free survival (DMFS) between the chemotherapy regimens were compared using inverse probability of treatment weighting (IPTW) and multivariable analyses.ResultsASP-based (versus non-ASP-based) regimens significantly improved 5-year OS (84.5% versus 73.2%, P = 0.021) and DMFS (84.4% versus 74.5%, P = 0.014) for intermediate- and high-risk patients, but not for low-risk patients in the setting of radiotherapy. Moreover, ASP-based regimens decreased DM, with a 5-year cumulative DM rate of 14.9% for ASP-based regimens compared with 25.1% (P = 0.014) for non-ASP-based regimens. The survival benefit of ASP-based chemotherapy and radiotherapy remained consistent after adjusting the confounding variables using IPTW and multivariate analyses; additional sensitivity analyses confirmed these results.ConclusionsThe findings provided support for ASP-based chemotherapy and radiotherapy as a first-line treatment strategy for intermediate- and high-risk early-stage ENKTCL.

Unrelated cord blood stem cell transplantation for high-risk/refractory childhood acute myeloid leukemia: a clinical analysis of 160 cases

目的探讨单份非血缘脐血干细胞移植（UCBT）治疗高危/难治儿童急性髓系白血病（AML）的疗效。方法对2008年6月至2018年12月期间接受UCBT的160例高危/难治AML（不含急性早幼粒细胞白血病）患儿进行回顾性分析。全部病例均采用清髓性预处理方案，应用环孢素A（CsA）联合短程霉酚酸酯（MMF）预防移植物抗宿主病（GVHD）。结果160例AML患儿中男103例、女57例，中位年龄7（1～14）岁，中位体重23（8～77）kg。移植后42 d中性粒细胞累积植入率为95.0％（95％CI 90.0％～97.5％），移植后120 d血小板累积植入率为85.5％（95％CI 83.3％～93.4％），中性粒细胞、血小板植入中位时间分别为移植后16（11～38）d、35（13～158）d。Ⅱ～Ⅳ、Ⅲ～Ⅳ度急性GVHD发生率分别为37.3％（95％CI 29.3％～45.2％）、27.3％（95％CI 20.0％～35.0％），慢性GVHD发生率为22.4％（95％CI 15.5％～28.7％）。可评估的移植后360 d移植相关死亡率（TRM）为13.1％（95％CI 8.4％～18.9％）。移植后5年累积复发率为13.8％（95％CI 8.5％～20.3％），无病生存（DFS）率为71.7％（95％CI 62.7％～77.8％）、总生存（OS）率为72.2％（95％CI 64.1％～78.7％），无GVHD无复发生存（GRFS）率为56.1％（95％CI 46.1％～64.9％）。移植前处于第1次完全缓解（CR1）期（95例）、第2次完全缓解（CR2）期（28例）、未缓解患者（37例）的移植后5年累积复发率分别为5.3％（95％CI 1.9％～11.1％）、19.9％（95％CI 6.9％～37.7％）、30.9％（95％CI 14.3％～49.2％）（P＝0.001），移植后5年OS率分别为79.9％（95％CI 70.3％～86.7％）、71.1％（95％CI 50.4％～84.4％）、52.9％（95％CI 33.0％～69.3％）（χ2＝7.552，P＝0.020）。结论UCBT是治愈高危/难治儿童AML安全、有效的治疗方法。第1次完全缓解期进行UCBT有利于改善预后。

Factors Predicting Locoregional Recurrence After Neoadjuvant Chemotherapy and Nipple-Sparing/Skin-Sparing Mastectomy With Immediate Breast Reconstruction.

BackgroundFew data are available on the risk factors of locoregional recurrence (LRR) after neoadjuvant chemotherapy (NACT) and immediate breast reconstruction (IBR) in breast cancer. Herein, we evaluated the factors predicting LRR in a large series of patients who underwent either nipple- (NSM) or skin-sparing mastectomy (SSM) with IBR after NACT.MethodsWe retrospectively analyzed 609 breast cancer patients who underwent NACT and NSM/SSM with IBR between February 2010 and June 2017. Factors associated with an increased risk of LRR were analyzed by univariate (chi-square or Fisher’s exact test) and multivariate (Cox proportional hazard regression model) analyses.ResultsDuring a median follow-up of 63 months, LRR as the first event occurred in 73 patients, and the 5-year cumulative LRR rate was 10.8%. Multivariate analysis revealed post-NACT Ki67 ≥ 10% [hazard ratio (HR), 2.208; 95% confidence interval (CI), 1.295-3.765; P = 0.004], high tumor grade (HR, 1.738; 95% CI, 1.038-2.908; P = 0.035), and presence of lymphovascular invasion (LVI) (HR, 1.725; 95% CI, 1.039-2.864; P = 0.035) as independently associated with increased LRR risk. The 10-year LRR rate was 8.5% for patients with none of the three associated risk factors, 11.6% with one factor, 25.1% with two factors, and 33.7% with all three factors (P < 0.001).ConclusionsPost-NACT Ki67 ≥ 10%, high tumor grade, and presence of LVI are independently associated with an increased risk of developing LRR after NACT and NSM/SSM with IBR. Future prospective trials are warranted to decrease the risk of LRR in patients with associated risk factors.

Outcomes of anus squamous cell carcinoma. Management of anus squamous cell carcinoma and recurrences

BackgroundLittle is known about the management of squamous cell carcinoma of the anal canal and its recurrence at a population level. The aim of this study was to draw a picture of management, recurrence and survival in squamous cell carcinoma of the anal canal. Material and methodsThe 5-year probability of recurrences was estimated using the cumulative incidence function to consider competing risks of death. Net survival was estimated and a multivariate survival analysis was performed. The study was conducted using data of the Burgundy Digestive Cancer Registry. Overall, 273 squamous cell carcinomas of the anal canal registered between 1998 and 2014 were considered. ResultsOverall, 80% of patients were treated with curative intent. Of these, 61% received chemoradiotherapy, 35% received radiotherapy and 4% received abdominoperineal resection alone. After these treatments, for cure the 5-year cumulative recurrence rate was 27% overall; it was 20% after chemoradiotherapy and 38% after radiotherapy. Five-year net survival was 71% overall; it was 81% after chemoradiotherapy and 55% after radiotherapy. Conclusions and relevanceChemoradiotherapy was highly effective in routine practice. We confirm that it is difficult to distinguish between persistent active disease and local inflammation due to radiotherapy. Squamous cell carcinoma of the anal canal recurrences remains a substantial problem, highlighting the interest of prolonged surveillance. Aggressive management of recurrences may be beneficial.

Clinical Implication of Gene Mutations in Children Myelodysplastic Syndromes

BackgroundMyelodysplastic syndromes (MDS) are typically diseases of older adults. Children with MDS may have distinct molecular and clinical features or reflect a demographic continuum.MethodWe studied a cohort of 81 pediatric patients with various subcategories of myelodysplastic syndrome and acute myeloid leukemia with myelodysplasia-related changes. All subjects provided informed consent in compliance with the Declaration of Helsinki. Bone marrow and blood samples were collected. DNA was extracted from the patients' marrow and wherever possible germline DNA was obtained from selected CD3+ T cells. We designed a targeted sequencing assay to test a panel of 417 genes. The panel contain reported gene associated with MDS and IBMFs that need be differentiated. The average coverage of targeted region was 98.15%, and the average sequencing depth was 1000×.ResultsClinical features ofpediatricmyelodysplastic syndromeIn the cohort, 51 (63%) were males and 30 (37%) females, with a median age of 6 years (range, 4months-18 years). According to the WHO 2008 criteria, 37 (46%) patients with refractory cytopenia of childhood (RCC), among them, 2 (3%) patients with RCUD, 30 (37%) RCMD, 2 (3%) RCMD-RS, and 3 (4%) MDS unclassifiable (MDS-U), 14 (17%) RAEB1, 16(20%) RARB2, 14 (17%) AML (MDS associated). Follow-up data was available for 73 (90%) subjects. Median follow-up for survivors was 18 months (range, 2-124). The 3-year and 5-year overall survival is 78% and 60%. The 3-year cumulative rate of leukemia transformation was 23.3%. According to the IPSSR, 2 (3%) patients were classified as very low risk group, 15 (21%) low risk , 14 (20%) intermediate risk, 15 (21%) high risk, and 24(34%) very high risk and the 3-year overall survival was 100%, 88%, 79%, 32% and 55% respectively (P=0.001). 29 (39.7%) subjects received bone marrow transplantation (BMT). the 3-year overall survival for patient with or without BMT was 96% and 45% (P=0.001). For patients with BMT, the IPSSR have no prognostic significance.Patterns of molecular lesionsWe found 397 mutations in 152 distinct genes with mutation loads varying from 10% to 100%. 17 (21%) subjects with 1 mutant gene, 17 (21%) with 2 mutant genes, 11 (14%) with 3 mutant genes and 14 (17%) with more than 3 mutant genes. 12 genes were mutated in greater than 5% of patients, namely SETBP1 15%, PTPN11 11%, ASXL1 10%, RUNX1 9%, WT1 9%, NRAS 7%, GATA2 7%, TET2 7%, NF1 7%, NPM1 6%, GATA 1 6%, U2AF1 6%. The distribution of gene mutations (>5%) observed in the entire study set was mirrored within the disease categories (Figure 1A).Compared to SETBP1 wildtypesubjects, SETBP1 mutated subjects were significantly associated with abnormal karyotype (P=0.019). Compared to PTPN11 wildtypesubjects, PTPN11 mutated subjects were significantly associated with younger than 6-year old and poor survival (3-year OS: 46% vs. 26%, P=0.031). However, WT1 or NPM1 mutated subjects were significantly associated with elder than 6-year old (P=0.002). GATA2 mutation was enriched for SETBP1 mutation (P=0.012, OR=7.33, 95%CI: 1.28-42.02), ASXL1 mutation (P=0.013, OR=14, 95%CI: 2.223-88.16), and RUNX1 mutation (P<0.001, OR=17.75, 95%CI: 2.68-117.7). More detailed association between different gene mutations is shown in Figure 1B.ConclusionCompared with gene mutation landscape in adult MDS, children with MDS have distinct gene mutation characteristics. Our study indicates some interesting association between different genes. The further identification has the potential to advance understanding of the pathogenesis of pediatric myelodysplasia. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Simple parameters predicting extrahepatic recurrence after curative hepatectomy for hepatocellular carcinoma

Extrahepatic recurrence (EHR) after curative hepatectomy for hepatocellular carcinoma (HCC) is associated with a poor prognosis. We investigated the features of EHR and identified its predictive factors. This retrospective study included 398 treatment-naive patients who underwent curative hepatectomy for HCC at two tertiary hospitals. Multivariate Cox-regression analysis was performed to identify the variables associated with EHR. EHR was diagnosed in 94 patients (23.6%) over a median follow-up period of 5.92 years, most commonly in the lungs (42.6%). The 5-/10-year cumulative rates of HCC recurrence and EHR were 63.0%/75.6% and 18.1%/35.0%, respectively. The median time to EHR was 2.06 years. Intrahepatic HCC recurrence was not observed in 38.3% of patients on EHR diagnosis. On multivariate analysis, pathologic modified Union for International Cancer Control stage (III, IVa), surgical margin involvement, tumor necrosis, sum of tumor size > 7 cm, and macrovascular invasion were predictive factors of EHR. Four risk levels and their respective EHR rates were defined as follows: very low risk, 1-/5-year, 3.1%/11.6%; low risk, 1-/5-year, 12.0%/27.7%; intermediate risk, 1-/5-year, 36.3%/60.9%; and high risk, 1-year, 100.0%. Our predictive model clarifies the clinical course of EHR and could improve the follow-up strategy to improve outcomes.

Hepatitis B core-related antigen predicts disease progression and hepatocellular carcinoma in hepatitis B e antigen-negative chronic hepatitis B patients.

The serum hepatitis B core-related antigen (HBcrAg) is considered a surrogate marker of the amount and activity of intrahepatic covalently closed circular DNA. This study aims to investigate the virological characteristics of HBcrAg in chronic hepatitis B (CHB) patients and to reveal the hepatocellular carcinoma (HCC) risk factors of hepatitis B e antigen (HBeAg)-negative patients. Hepatitis B core-related antigen was measured in 245 naive CHB patients before receiving nucleoside/nucleotide analog (NA) therapy. All patients were receiving NA (entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide) continuously for more than 1year until the end of follow-up, and they did not have a history of HCC. Hepatitis B viral status was compared between 106 HBeAg-positive and 139 HBeAg-negative patients. Median HBcrAg levels were significantly higher in HBeAg-positive patients than in HBeAg-negative patients (>6.8 vs 3.7log U/mL, P<0.01). In HBeAg-negative patients, higher HBcrAg levels were associated with cirrhosis (119 chronic hepatitis/20 cirrhosis=3.5/4.7log U/mL, P=0.03) and higher serum hepatitis B virus DNA. During a median follow-up of 5.28 (1.03-12.0) years, the 5-year cumulative HCC incidence rate was 5.4% in the HBeAg-negative cohort. In the multivariate Cox regression analysis, higher HBcrAg levels at 1year were independent predictive factors for HCC development in HBeAg-negative patients who received NA therapy (cutoff value, 4.1log U/mL; hazard ratio, 6.749; 95% confidence interval, 1.334-34.15, P<0.01) and even in non-cirrhosis patients. Hepatitis B core-related antigen was useful for understanding disease progression in CHB patients and for stratifying the risk for carcinogenesis in HBeAg-negative patients receiving NA therapy.

Outcomes in Patients With Chronic Renal Failure on Hemodialysis After Aortic Valve or Root Replacement

The long-term survival and reoperation rate in chronic renal failure (CRF) on hemodialysis (HD) patients after aortic valve/root replacement (AVR/ARR) with a stentless bioprosthesis is unknown. From 1992-2015, 1941 patients underwent AVR/ARR with stentless valve for primary indications of aortic stenosis/insufficiency, root aneurysm, and acute type A aortic dissection, including 93 CRF-HD (64 new-onset postoperative HD, and 29 preoperative HD) and 1848 non-CRF-HD. Data was obtained from the STS database, retrospective chart review, administered surveys and national death index data. Compared to the non-CRF-HD group, the CRF-HD group had significantly higher incidence of diabetes mellitus (28 vs 18%), CAD (49 vs 38%), COPD (31 vs 16%), NYHA class IV (12 vs 4%), atrial fibrillation (24 vs 12%), and previous cardiac surgery (27 vs 16%). Postoperatively, CRF-HD group had a higher reoperation for bleeding (10 vs 4%), length of hospital stays (20 vs 7 days), and operative mortality (23 vs 2.3%), all p < 0.01. The odds ratio of CRF-HD for operative mortality was 8.97. The long-term survival was worse in CRF-HD group than that in non-CRF-HD group [8-year survival: 31% vs 70%, p < 0.0001]. The hazard ratio of CRF-HD for long-term mortality was 2.4. The 10-year cumulative reoperation rate for structural valve deterioration in the CRF-HD group was 6.0% vs 5.0% in the non-CRF-HD group, p=0.74. Surgeons should consider poor short- and long-term outcomes of patients with high risk of being on dialysis when offering aortic valve/root replacement. Bioprosthesis could be a good option in this patient population.

The Phenomenon of Gene Rearrangement is Frequently Associated with TP53 Mutations and Poor Disease-Free Survival in Hepatocellular Carcinoma.

PurposeGene rearrangements (GRs) have been reported to be related to adverse prognosis in some tumours, but the relationship in hepatocellular carcinoma (HCC) remains less studied. The objective of our study was to explore the clinicopathological characteristics and prognosis of HCC patients (HCCs) with GRs (GR-HCCs).Patients and MethodsThis retrospective study included 297 HCCs who underwent hepatectomy and had their tumours sequenced by next-generation sequencing. Categorical variables between groups were compared by the chi-square test. The impact of variables on disease-free survival (DFS) and survival after relapse (SAR) was analysed by the Kaplan–Meier method and Cox regression.ResultsWe observed four repetitive GR events in 297 HCCs: BRD9/TERT, ARID2/intergenic, CDKN2A/intergenic and OBSCN truncation. GR-HCCs frequently presented with low tumour differentiation, tumour necrosis, microvascular invasion, elevated AFP and gene mutations (TP53, NTRK3 and BRD9). The 1-, 2-, and 3-year cumulative DFS rates in GR-HCCs were 45.1%, 31.9%, 31.9%, respectively, which were significantly lower than those of GR-negative HCCs (NGR-HCCs) (72.5%, 57.9%, and 49.0%, respectively; P = 0.001). GR was identified as an independent risk factor for inferior DFS in HCCs (HR = 1.980, 95% CI = 1.246–3.147; P = 0.004). However, there was no significant difference in SAR between GR-HCCs and NGR-HCCs receiving targeted therapy or immunotherapy.ConclusionGR is frequently associated with TP53 mutations and significantly affects DFS following radical resection for HCC. We recommend that GR-HCCs should be closely followed up as a high-risk group for postoperative recurrence.

MicroRNAs as predictors of future endometrial malignancies in endometrial hyperplasia without atypia.

e17563 Background: The histological criteria of predicting risk of progression of endometrial hyperplasia (EH) to endometrial cancer (EC) is based on the degree of architectural crowding and nuclear atypia. We aim to investigate the cumulative rate of progression to EC in simple or complex hyperplasia without atypia (SH/CH-nonA) and the molecular biomarkers for risk of developing EC in women with SH/CH-nonA. Methods: EH tissues of EC patients with preceding SH/CH-nonA (case) were compared to SH/CH-nonA patients without progression to EC (control) using miRNA array, followed by reverse transcription and quantitative real-time polymerase chain reaction (RT-qPCR), and verified in an independent cohort. Results: The 10-year and 15-year cumulative rates were 8% and 10%, respectively by the hospital medical records. The median time from EH to EC was 8.71 years (range, 0.55-19.84). Twenty miRNAs (p &lt; 0.05, fold change &gt; 4) were significantly different in SH/CH-nonA cases (n = 6) compared to SH/CH-nonA controls (n = 12) by miRNA array. Multiplex RT-qPCR validation (51 SH/CH-nonA controls and 19 SH/CH-nonA cases) selected miR30a-3p, miR141, miR200a, and miR200b. Area under the curve values for tissue miR30a-3p (p = 0.043), miR141(p = 0.003), miR-200a (p &lt; 0.001), and miR200b (p = 0.004) in discriminating cases from controls were 0.658, 0.734, 0.811, and 0.710, and the sensitivity and specificity rates were 56.9% and 76.5%, 73.7% and 74.5%, and 68.4% and 100%, 47.4% and 100%, respectively. Conclusions: MiR30a-3p, miR141, miR-200a, and miR200b are useful tissue biomarkers for predicting future risk of developing EC for patients with SH/CH-nonA.

Stereotactic ablative radiotherapy in operable stage I NSCLC patients: Long-term results of the expanded STARS clinical trial.

8506 Background: We published a pooled analysis of 2 randomized trials (STARS/ROSEL) that compared lobectomy with mediastinal lymph node dissection (L-MLND) vs stereotactic ablative radiotherapy (SABR) in operable stage I NSCLC. There were no significant differences in disease progression but significantly higher 3-year overall survival (OS) in the SABR arm (95% vs 79%). Owing to concerns regarding the small sample size (n = 58), short follow-up (3 years), and non-uniform use of video-assisted thoracoscopic surgery (VATS), we expanded the STARS protocol to a single-arm SABR trial with a protocol-specified comparison to a published, longitudinally-followed institutional cohort of stage IA NSCLC status post VATS L-MLND (n = 229). Methods: Inclusion criteria were stage IA NSCLC (≤3 cm, N0M0 and staged by PET/CT with EBUS) with Zubrod performance status (PS) 0-2, baseline FEV1 &gt; 40% and DLCO &gt; 40% and deemed operable by a multidisciplinary team. SABR utilized 4-dimensional CT simulation and volumetric image guidance; 54 Gy in 3 fractions were delivered to planning target volumes (PTVs) located peripherally, or 50 Gy in 4 fractions to more central PTVs. All patients were followed by chest CT every three months for the first two years, every 6 months for another three years, and then annually. Non-inferiority of SABR could be claimed if the 3-year OS was not lower than the historical VATS L-MLND cohort by more than 12%. We conducted a risk-factor matched comparison study of the primary outcome between the SABR and the historical VATS L-MLND. Results: The median follow-up among the 80 SABR patients was 61 months (range, 34-79 months). The OS and progression-free survival (PFS) were 91% (95% CI: 85̃98%) and 80% (95% CI: 72̃89%) at 3 years, and 87% (95% CI: 79̃95%) and 77% (95% CI: 68̃87%) at 5 years, respectively. The 5-year cumulative incidence rate counting death as competing risk was 6.3% (95% CI: 2.3̃13.2%) local, 12.5% (95% CI: 6.4̃20.8%) regional, and 8.8% (95% CI: 3.8̃16.2%) distant (any recurrence 17.6% (95% CI: 10.1̃26.7%)). The 5 year cumulative incidence rate of second lung primary was 6.9% (95% CI: 2.5̃14.6%). There were 1.3% grade 3 and no grade 4-5 toxicities. The propensity score matched (age, gender, tumor size, histology, PS) comparison of SABR vs VATS L-MLND revealed no significant differences in PFS (p = 0.063), lung cancer-specific survival (p = 0.075), or cumulative incidence rates of local (p = 0.54), regional (p = 0.97), or distant failures (p = 0.33). The SABR arm was associated with significantly higher OS (91% vs 82% at 3 years and 87% vs 72% at 5 years; p = 0.012 from log-rank test). The hazard ratio was 0.411 (95% CI: 0.193̃0.875; p = 0.021). Conclusions: The long-term OS and PFS of SABR is not inferior to VATS L-MLND for operable stage IA NSCLC. SABR remains a promising approach for this population, but multidisciplinary management is strongly recommended. Clinical trial information: NCT02357992.

Growth of vestibular schwannoma: long-term follow-up study using survival analysis.

A vestibular schwannoma (VS) is a benign nerve sheath tumor derived from the vestibular nerves. The growth rate of VS during long-term follow-up has not yet been fully evaluated. We aimed to investigate the growth rate of newly diagnosed VS and the related predictive factors for tumor growth. A retrospective review was performed using VS patients who underwent at least two magnetic resonance imaging (MRI) scans before tumor growth was observed. Tumor growth was defined as a size increase of more than 2mm in the longest diameter of the tumor. To assess the growth rate of VS and related factors, we assessed tumor growth using survival analysis. Survival analysis to assess the growth rate and Cox regression analysis were performed to find related factors. The study included 118 patients. The mean age of patients was 57.0 ± 12.9years. During the observation period, the 5-year cumulative growth incidence rate was 41.3% by survival analysis. Extrameatal tumor location and hearing loss were found to be associated with an increased hazard ratio (HR) for tumor growth. After long-term observation of VS, 41.3% of VS patients presented cumulative growth incidence rate in the first 5years after diagnosis. Extrameatal tumor location and hearing changes were related to subsequent tumor growth.

Percutaneous Microwave Ablation Versus Open Surgical Resection for Colorectal Cancer Liver Metastasis.

PurposeTo compare the therapeutic outcomes between open surgical resection (OSR) and percutaneous microwave ablation (PMWA) for colorectal liver metastasis (CRLM) ≤3 cm.MethodsIn this retrospective study, 200 consecutive patients with 306 CRLMs were reviewed. Overall survival (OS), disease-free survival (DFS), local tumour progression (LTP), intrahepatic distant recurrence, and extrahepatic metastasis were analysed to compare the therapeutic efficacy. Cox proportional hazards regression analysis was used to identify the prognostic factors for OS and DFS. Major complications and postoperative hospital stay were also assessed.ResultThe 1-, 3-, and 5-year OS rates were 91.6%, 64.1%, and 46.3%, respectively, in the PMWA group and 89.7%, 62.4% and 44.7%, respectively, in the OSR group (P=0.839). The 1-, 3-, and 5-year DFS rates were 61.9%, 44.8%, and 41.3%, respectively, in the PMWA group and 58.1%, 24.4%, and 18.3%, respectively, in the OSR group (P =0.066). The two groups had comparable 5-year cumulative rates of intrahepatic distant recurrence (P=0.627) and extrahepatic metastasis (P=0.884). The 5-year cumulative LTP rate was lower in the OSR group than in the PMWA group (P=0.023). The rate of major complications was higher in the OSR group than in the PMWA group (P =0.025), and the length of hospital stay after treatment was shorter in the PMWA group (P<0.001).ConclusionThere were no significant differences in OS or DFS between the two groups. PMWA was associated with increased LTP, fewer postoperative days and fewer major complications.

Identification of Patients with Locally Advanced Rectal Cancer in Whom Preoperative Radiotherapy Can Be Omitted: A Multicenter Retrospective Study at Yokohama Clinical Oncology Group (YCOG1307).

Objectives: The present study aimed to identify patients with locally advanced rectal cancer in whom preoperative radiotherapy (RT) can be omitted. Methods: This study was a retrospective multi-institutional study for patients with pathological stage II and III rectal cancer who underwent surgery without preoperative therapy between January 2008 and December 2012. Clinicopathological factors were examined by univariate and multivariate analyses to clarify independent risk factors of local recurrence (LR). Results: The 5-year cumulative local recurrence rate (LRR) of 815 patients was 11.2%. Independent predictive factors of LR were determined by a multivariate analysis to be a tumor location of <10 cm from the anal verge, a tumor diameter of ≥50 mm, undifferentiated histological type, and advanced T-N substage (T3N+ or T4Nany). In lower rectal cancer located <10 cm from the anal verge (n = 510), the 5-year cumulative LRR of patients without any remaining three factors was 4.4%, with one factor was 13.0%, with two factors was 22.2%, and with all three factors was 41.6%. Conclusions: Preoperative RT may be omitted in patients with lower rectal cancer with no risk factors. However, in addition to the present risk factors, we need to further examine the extramural vascular invasion (EMVI) status and circumferential resection margin (CRM) using magnetic resonance imaging (MRI) findings. The trial was registered with UMIN Clinical Trails Registry, number 000006039.

A Survivorship-Period-Cohort Model for Cancer Survival: Application to Liver Cancer in Taiwan, 1997-2016.

Monitoring survival in cancer is a common concern for patients, physicians, and public health researchers. The traditional cohort approach for monitoring cancer prognosis has a timeliness problem. In this paper, we propose a survivorship-period-cohort (SPC) model for examining the effects of survivorship, period, and year-of-diagnosis cohort on cancer prognosis and for predicting future trends in cancer survival. We used the developed SPC model to evaluate the relative survival (RS) of patients with liver cancer in Taiwan (diagnosed from 1997 to 2016) and to predict future trends in RS by imputing incomplete follow-up data for recently diagnosed patient cohorts. We used cross-validation to select the extrapolation method and bootstrapping to estimate the 95% confidence interval for RS. We found that 5-year cumulative RS increased for both men and women with liver cancer diagnosed after 2003. For patients diagnosed before 2010, the 5-year cumulative RS rate for men was lower than that for women; thereafter, the rates were better for men than for women. The SPC model can help elucidate the effects of survivorship, period, and year-of-diagnosis cohort effects on cancer prognosis. Moreover, the SPC model can be used to monitor cancer prognosis in real time and predict future trends; thus, we recommend its use.

Predictive performance of newer Asian hepatocellular carcinoma risk scores in treated Caucasians with chronic hepatitis B

Background & AimsRecently, several risk scores for prediction of hepatocellular carcinoma (HCC) were developed in cohorts of treated Asian patients with chronic hepatitis B (CHB), but they have not been assessed in non-Asian patients. We evaluated the predictability and comparative utility of our PAGE-B and recent Asian HCC risk scores in nucleos(t)ide analogue (NA)-treated adult Caucasian patients with CHB, with or without well-documented compensated cirrhosis but not previous diagnosis of HCC.MethodsWe included 1,951 patients treated with entecavir/tenofovir and followed up for a median of 7.6 years. The c-statistic was used to estimate the predictability of PAGE-B, HCC-Rescue, CAMD, mPAGE-B, and AASL score for HCC development within 5 or 10 years. The low- and high-risk group cut-offs were used for estimation of negative (NPV) and positive predictive values (PPV), respectively.ResultsHCC developed in 103/1,951 (5.3%) patients during the first 5 years and in another 39/1,428 (2.7%) patients between years 5 and 10. The 3-, 5-, and 10-year cumulative HCC rates were 3.3%, 5.9%, and 9.6%, respectively. All scores offered good 5- and 10-year HCC prediction (c-statistic: 0.78–0.82). NPVs were always >99% (99.3–100%), whereas PPV ranged between 13% and 24%.ConclusionsIn NA-treated Caucasian patients with CHB including compensated cirrhosis, HCC risk scores developed in NA-treated Asian patients offer good 5- and 10-year HCC predictability, similar to that of PAGE-B. PAGE-B and mPAGE-B scores are simpler in clinical practice, as they do not require an accurate diagnosis of cirrhosis, but the addition of albumin in mPAGE-B score does not seem to offer an advantage in patients with well compensated liver disease.Lay summarySeveral risk scores for prediction of hepatocellular carcinoma (HCC) were recently developed in cohorts of treated Asian patients with chronic hepatitis B (CHB). In Caucasian patients with CHB treated with oral antivirals, newer Asian HCC risk scores offer good 5- and 10-year HCC predictability, similar to that of PAGE-B. For clinical practice, PAGE-B and mPAGE-B scores are simpler, as they do not require an accurate diagnosis of cirrhosis.

The effect of body mass index on the outcomes of cementless medial mobile-bearing unicompartmental knee replacements

PurposeGiven an increasingly overweight population, unicompartmental knee replacements (UKRs) are being performed in patients with higher body mass indices (BMIs). There are concerns that cemented fixation will not last. Cementless fixation may offer a solution, but the long term results in different BMI groups has not been assessed. We studied the effect of BMI on the outcomes of cementless UKRs.MethodsA prospective cohort of 1000 medial cementless mobile-bearing UKR with a mean follow up of 6.6 years (SD 2.7) were analysed. UKRs were categorised into four BMI groups: (1) ≥ 18.5 to < 25 kg/m2 (normal), (2) 25 to < 30 kg/m2 (overweight), (3) 30 to < 35 kg/m2 (obese class 1) and (4) ≥ 35 kg/m2 (obese class 2). Implant survival was assessed using endpoints reoperation and revision. Functional outcomes were assessed.ResultsTen-year cumulative revision rate for the normal (n = 186), overweight (n = 434), obese class 1 (n = 213) and obese class 2 (n = 127) groups were 1.8% (CI 0.4–7.4), 2.6% (CI 1.3–5.1), 3.8% (CI 1.5–9.2) and 1.7% (CI 0.4–6.8) with no significant differences between groups (p = 0.79). The 10-year cumulative reoperation rates were 2.7% (CI 0.8–8.2), 3.8% (CI 2.2–6.6), 5.2% (CI 2.5–10.7) and 1.7% (CI 0.4–6.8) with no significant differences between groups (p = 0.44). The 10-year median Oxford Knee Score were 43.0, 46.0, 44.0 and 38.0 respectively.ConclusionCementless mobile-bearing UKR has low 10-year reoperation and revision rates across in all BMI groups, and there are no significant differences between the groups. Although higher BMI groups had slightly worse functional outcomes, the improvement in function compared to preoperatively tended to be better. This study suggests that BMI should not be considered a contraindication for the cementless mobile-bearing UKR.

Effect of smoking status and programmed death-ligand 1 expression on the microenvironment and malignant transformation of oral leukoplakia: A retrospective cohort study.

Tobacco smoking is associated with an increased risk of oral leukoplakia and head and neck cancer. Although it has recently been reported that the establishment of an immunosuppressive microenvironment in oral potentially malignant disorders may lead to malignant transformation, it is unclear whether the microenvironments of oral potentially malignant disorders differ according to smoking status. We examined differences in programmed death-ligand 1 (PD-L1) expression and subepithelial CD163+ TAM and CD8+ cell/lymphocyte counts in the microenvironment of oral leukoplakia of smoking and non-smoking patients and investigated their associations with malignant transformation. Pathology reports and original biopsy request forms from 1995–2015 were retrospectively reviewed. Lesions clinically characterized as white plaques/lesions of the oral mucosa and pathologically diagnosed as oral epithelial dysplasia were included. Immunohistochemistry was performed to evaluate PD-L1 expression and subepithelial CD163+/CD8+ cell counts. The significance of prognostic factors in predicting malignant transformation was determined using Cox regression analysis. Statistical significance was defined as P<0.05. In total, 200 patients with oral leukoplakia were selected. The mean age at diagnosis was higher in non-smoking patients (n = 141; 66.9 years) than in smoking patients (n = 59; 60.5 years). The 5-year cumulative malignant transformation rate was higher in non-smoking patients than in smoking patients (9.3% vs. 3.0%, respectively). Oral leukoplakia was associated with significantly higher PD-L1 expression and increased numbers of subepithelial CD163+ cells in the non-smoking group compared with the smoking group. Non-smoking-related oral leukoplakia with positive PD-L1 expression was associated with a 6.97-fold (95% confidence interval: 2.14–22.7) increased risk of malignant transformation. The microenvironment of oral leukoplakia differed according to smoking status. A combination of smoking status and PD-L1 expression may predict malignant transformation in oral leukoplakia patients. This study highlights the importance of understanding the interaction between smoking and the microenvironment in oral leukoplakia.