Radiation-induced undifferentiated pleomorphic sarcoma after radiation therapy for a desmoid tumour

Radiation-induced sarcoma is a long-term complication of radiation therapy. The most common secondary neoplasia is the undifferentiated pleomorphic sarcoma, which is usually described in the deep soft tissue of the trunk or extremities. Radiation-induced sarcomas have a poor prognosis. An early diagnosis and management are needed to improve the survival rate of such patients. We presently report a case of a radiation-induced undifferentiated pleomorphic sarcoma of the left gluteus maximus muscle, which developed 25 years after an initial diagnosis of aggressive fibromatosis and 21 years after a tumour recurrence. This case study illustrates the risk of developing a sarcoma in a radiation field and the need for long-term follow-up after radiation therapy. Unnecessary radiation therapy, in particular in the case of benign conditions in young patients, should be avoided.     

肾脏原发性未分化多形性肉瘤MSCT诊断及病理对照研究

目的:探讨肾脏原发性未分化多形性肉瘤的临床、病理特征及多层螺旋CT表现.方法:回顾性分析8例经病理证实的肾脏原发性未分化多形性肉瘤的临床病理资料及CT影像特征.结果:8例均为单发,左肾6例,右肾2例,5例病灶主体位于肾上极,3例位于肾下极.5例病灶主体位于肾实质,2例侵犯肾窦,1例主体位于肾窦.5例伴有同侧不同程度肾积水,2例伴有明显肾周侵犯,1例肾静脉癌栓形成.7例形态不规则、边界不清,1例类圆形、边界清晰.CT平扫均表现为不均匀等/低混杂密度,1例病灶内可见斑点状、结节状钙化;增强扫描8例皮质期均表现为不均匀轻至中度强化,强化程度低于肾皮质;6例实质期、肾盂期持续强化,2例强化程度下降.结论:肾脏原发性未分化多形性肉瘤易误诊,CT增强扫描有一定的特征性,主要依靠病理和免疫组化确诊.     

Neutrophil-to-lymphocyte ratio as a prognostic factor for survival in patients with colorectal liver metastases: A systematic review

BACKGROUNDThe inflammatory response to tumor has been proven to be closely related to the prognosis of colorectal cancer. Neutrophil to lymphocyte ratio (NLR) is a widely available inflammatory biomarker that may have prognostic value for patients with colorectal liver metastasis (CRLM).AIMTo assess the role of NLR as a prognostic factor of survival and tumor recurrence in patients with CRLM.METHODSA systematic literature search of PubMed, Cochrane Library and clinicaltrials.gov was conducted by two independent researchers in order to minimize potential errors and bias. Conflicts were discussed and settled between three researchers. Studies including patients undergoing different types of medical interventions for the treatment of CRLM and evaluating the correlation between pretreatment NLR and disease-free survival (DFS) and overall survival (OS) were included in the review. Nineteen studies, involving 3283 patients matched our inclusion criteria.RESULTSIn the studies included, NLR was measured before the intervention and the NLR thresholds ranged between 1.9 and 7.26. Most studies used 5 as the cut-off value. Liver metastases were treated with hepatectomy with or without chemotherapy regimens in 13 studies and with radiofrequency ablation, radioembolization, chemoembolization or solely with chemotherapy in 6 studies. High NLR was associated with decreased OS and DFS after liver resection or other medical intervention. Moreover, high NLR was associated with poor chemosensitivity. On the contrary, CRLM patients with low pretreatment NLR demonstrated improved OS and DFS. NLR could potentially be used as a predictive factor of survival and tumor recurrence in patients with CRLM treated with interventions of any modality, including surgery, chemotherapy and ablative techniques.CONCLUSIONNLR is an inflammatory biomarker that demonstrates considerable prognostic value. Elevated pretreatment NLR is associated with poor OS and DFS in patients with CRLM who are submitted to different treatments.     

Neurotensin receptor 1 is a new therapeutic target for human undifferentiated pleomorphic sarcoma growth

Undifferentiated pleomorphic sarcoma (UPS) is the second most common soft tissue sarcoma. For patients with unresectable or metastatic disease, chemotherapies are considered, but in many cases they are not curative. There is a need to identify specific molecular dysregulations that can be therapeutic targets. We focused on neurotensin receptor 1 (NTSR1), which belongs to the G‐protein‐coupled receptor. NTSR1 expression was upregulated in specimens from patients with UPS. Real‐time polymerase chain reaction showed that expression of NTSR1 messenger RNA was 5‐ to 7‐fold increased in UPS cells compared with myoblasts. Western blot showed a high expression of NTSR1 protein in UPS cell lines. Knockdown of NTSR1 prevented UPS cell proliferation and invasion. We confirmed that SR48692, an inhibitor of NTSR1, exhibited antitumor activities in UPS cells. The combination index showed that SR48692 and standard chemotherapeutic drugs prevented UPS cell proliferation synergistically. Mouse xenograft models showed that SR48692 inhibited extracellular signal‐regulated kinase phosphorylation and enhanced the response to standard chemotherapeutic drugs. Inhibition of NTSR1 improved the effect of standard chemotherapeutic drugs for UPS. SR48692 may be a new drug for targeted UPS therapy.     

Identifying actionable variants using next generation sequencing in patients with a historical diagnosis of undifferentiated pleomorphic sarcoma

There are limited data regarding the molecular characterization of undifferentiated pleomorphic sarcomas (UPS; formerly malignant fibrous histiocytoma). This study aimed to investigate the utility of next generation sequencing (NGS) in UPS to identify subsets of patients who harbour actionable mutations. Patients diagnosed with UPS underwent pathological re‐evaluation by a pathologist specializing in sarcoma. Tumor DNA was isolated from archived fresh frozen tissue samples and genotyped using NGS with the Illumina MiSeq TruSeq Amplicon Cancer Panel (48 genes, 212 amplicons). In total, 95 patients initially classified with UPS were identified. Following pathology re‐review the histological subtypes were reclassified to include: Myxofibrosarcoma (MFS, N = 44); UPS(N = 18); and Others (N = 27; including undifferentiated spindle cell sarcoma (N = 15) and dedifferentiated liposarcoma (N = 6)). Seven cases were excluded from further analysis for other reasons. Baseline demographics of the finalized cohort (N = 88) showed a median age of 66 years (32–95), primarily with stage I–III disease (92%) and high‐grade (86%) lesions. Somatic mutations were identified in 31 cases (35%)(Total mutations = 36: solitary mutation(n = 27); two mutations( =n = 3); three mutations(n = 1)). The most commonly identified mutations were in TP53 (n = 24), ATM (n = 3) and PIK3CA (n = 2). Three of 43 patients with MFS and one of 18 patients with UPS had clinically relevant mutations, mainly related to biomarkers of prediction of response; however few had targetable driver mutations. Somatic mutation status did not influence disease free or overall survival. Based on the small number of clinically relevant mutations, these data do not support the routine use of targeted NGS panels outside of research protocols in UPS.     

The neutrophil-to-lymphocyte ratio (NLR) predicts short-term and long-term outcomes in gastric cancer patients

Background

The preoperative neutrophil-to-lymphocyte ratio (NLR) is a well-known prognostic marker for gastric cancer patients. However, the utility of the NLR in predicting short-term outcomes in gastric cancer patients remains unclear. Here, we investigated whether the preoperative NLR is a predictor of short-term outcomes in gastric cancer patients.

Neutrophil/lymphocyte ratio is associated with survival in synovial sarcoma

Background

Synovial sarcoma is a rare malignant soft tissue tumor, more common in adolescents and young adults and entails a poor prognosis. Several good prognostic factors have been well established such as age less than 25, size less than 5?cm and absence of a poorly differentiated component. Inflammation has a well-established role in tumor proliferation and survival. The aim of this study was to investigate the prognostic significance of the neutrophil/lymphocyte ratio (NLR) in a large cohort of synovial sarcoma patients.

Neutrophil-to-lymphocyte ratio as a prognostic marker in locally advanced nasopharyngeal carcinoma: A pooled analysis of two randomised controlled trials

PurposeTo assess the prognostic value of neutrophil-to-lymphocyte ratio (NLR) in patients with International Union Against Cancer (UICC)–staged III/IVA,B nasopharyngeal carcinoma (NPC), who were enrolled into two randomised controlled trials of concurrent/adjuvant chemotherapy when added to radiotherapy (SQNP01), and induction chemotherapy when added to chemoradiotherapy (NCC0901).Material and methodsA post hoc analysis of pooled cohorts from SQNP01 (N = 221) and NCC0901 (N = 172) was performed. We employed a threshold of pre-treatment NLR = 3.0 (median) to stratify patients. Survival outcomes were compared using log-rank test. Multivariable Cox regression analyses were performed to assess association between NLR and overall survival (OS), disease-free survival (DFS), distant metastasis–free survival (DMFS), and locoregional recurrence–free survival (LRFS).ResultsHigh NLR (≥3.0) was associated with advanced T-status (p = 0.002), N-status (p = 0.002), overall UICC stage (p = 0.004), and high pre-treatment Epstein–Barr virus DNA titre (p = 0.001). High NLR was not associated with OS (0.94 [0.67–1.32], p = 0.7), DFS (0.98 [0.73–1.33], p = 0.9), DMFS (1.02 [0.66–1.57], p = 0.9), and LRFS (1.37 [0.84–2.22], p = 0.2) on univariable and multivariable analyses, while conventional clinical indices (T-status, N-status, and overall UICC stage) were prognostic of clinical outcomes. High NLR also did not predict for a treatment effect with the experimental arms in both trials.ConclusionOur pooled analyses that were confined to a homogenous patient population of locally advanced NPC do not suggest that NLR adds prognostic value to conventional clinical indices in identifying patients with unfavourable disease.     

Alveolar space filling ratio as a favorable prognostic factor in small peripheral squamous cell carcinoma of the lung

Introduction

Squamous cell carcinomas (SqCCs) of the lung can be divided into two types according to the location of primary site; one is central type and another is peripheral type. Many reports on the central type revealed the clinicopathological characteristics relating carcinogenesis, therapeutics and prognosis. On the other hand, those on the peripheral type are very a few and prognostic indicators of peripheral type have not been enough elucidated. The aim of this study was to clarify clinicopathological prognostic factors of small peripheral SqCCs of the lung 30 mm or less.

Materials and methods

We evaluated various 15 clinicopathological parameters in 81 patients with peripheral type SqCCs, which are defined as tumors located in or more peripheral from the third branching bronchus, measuring 30 mm or less in diameter.

Results

Univariate analyses were performed using the log lank test and multivariate analyses using logistic regression model. As a result, two factors had a statistically significant influence on outcome of the patients in the univariate analysis; no relapse was observed in the patients with the ratio of alveolar space filling (ASF) area to tumor area of 70% or more and the maximum diameter of invasive area measuring 10 mm or less in size (P = 0.0214, P = 0.0373, respectively). Meanwhile, multivariate analysis showed that the ASF ratio of 70% or more significantly affected the outcome of the patients (P = 0.0337), however the maximum diameter of invasive area did not (P = 0.2136). We could not show the unfavorable prognostic factor contributory to tumor relapse.

Conclusions

We have shown that the ASF ratio is a significantly favorable prognostic factor for small peripheral type. Especially the focally invasive tumors with ASF ratio of 70% or more might be classified as “a microinvasive carcinoma” of the peripheral SqCCs of the lung and tumors with ASF ratio 100% as noninvasive carcinoma.     

The lymph node ratio as prognostic factor in node-positive breast cancer

BACKGROUND AND PURPOSE: The clinical records of the node-positive breast cancer patients treated at our department were reviewed, to evaluate if there is a correlation between the ratio of involved axillary lymph nodes and the overall and cause specific survival. PATIENTS AND METHODS: From 1984 until July 2001, 2073 files from patients with an invasive breast carcinoma were submitted to retrospective analyses. In 810 cases, a node positive status was diagnosed. All pT-stages were included. The total number of dissected nodes (pNtot) and the number of involved nodes (pN+) were available for 741 patients. The ratio of nodal involvement (pN+%) was categorized into three groups, pN+%< or =10% (n = 212) between 11 and 50% (n = 346) and between 51 and 100% (n = 183). RESULTS: The actuarial overall survival (OS) at 5 and 10 years was, respectively, 78.2 and 59.1%. Cause specific survival (CSS) rates were, respectively, 83.6 and 69.1%. In univariate analyses, age (P = 0.01), grade (P = 0.02), pT-stage (P < 0.0001), chemotherapy (P = 0.0002), the number of involved nodes < or =3 versus >3 (pN+) (P < 0.0001) and ratio pN+% (P < 0.0001) were associated significantly with overall survival. A multivariate analysis using the Cox proportional hazards model found that pN+% was the most significant prognostic factor; pN+lost significance when pN+% was taken into account. CONCLUSIONS: The percentage of positive lymph nodes in an axillary lymph node dissection appears to be an important prognostic factor for survival. The nodes ratio improved on the absolute numbers of involved axillary lymph nodes for assessment of prognosis.     

Prognostic value of inflammation-based markers in patients with pancreatic cancer administered gemcitabine and erlotinib

AIM: To evaluate the value of systemic inflammation-based markers as prognostic factors for advanced pancreatic cancer (PC). METHODS: Data from 82 patients who underwent combination chemotherapy with gemcitabine and erlotinib for PC from 2011 to 2014 were collected retrospectively. Data that included the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio, and the C-reactive protein (CRP)-to-albumin (CRP/Alb) ratio were analyzed. Kaplan-Meier curves, and univariate and multivariate Cox proportional hazards regression analyses were used to identify the prognostic factors associated with progression-free survival (PFS) and overall survival (OS). RESULTS: The univariate analysis demonstrated the prognostic value of the NLR (P = 0.049) and the CRP/Alb ratio (P = 0.047) in relation to PFS, and a positive relationship between an increase in inflammation-based markers and a poor prognosis in relation to OS. The multivariate analysis determined that an increased NLR (hazard ratio = 2.76, 95%CI: 1.33-5.75, P = 0.007) is an independent prognostic factor for poor OS. There was no association between the PLR and the patients’ prognoses in those who had received chemotherapy that comprised gemcitabine and erlotinib in combination. The Kaplan-Meier method and the log-rank test determined significantly worse outcomes in relation to PFS and OS in patients with an NLR > 5 or a CRP/Alb ratio > 5. CONCLUSION: Systemic inflammation-based markers, including increases in the NLR and the CRP/Alb ratio, may be useful for predicting PC prognoses.     

单中心高度恶性软组织肉瘤的诊疗经验

背景与目的：高度恶性软组织肉瘤是一类转移率高、预后差的恶性肿瘤。该研究总结单中心高度恶性软组织肉瘤的治疗经验,以指导制定这类肿瘤患者的个体化治疗方案。方法：对2000年7月—2014年7月在北京大学人民医院骨与软组织治疗中心接受手术及辅助治疗的473例高度恶性软组织肉瘤患者的临床资料进行回顾性分析,随访这些患者复发、转移及生存情况,分析影响预后的因素。结果：共有400例（84.6%）患者接受了保肢治疗。103例患者出现局部复发,148例患者出现肺、骨等远处转移,419例（88.6%）患者接受广泛性切除。370例患者接受术后化疗,153例患者接受局部放疗。平均随访时间为46.9个月（8.0~127.0个月）。随访期间114例患者死亡。3、5及10年总生存率分别为82.6%、69.0%及58.7%。统计学分析显示,肿瘤的组织学类型、辅助化疗及转移情况是影响患者预后的危险因素。结论：对高风险的肿瘤患者应进行积极的辅助治疗,包括通过化疗降低转移风险和局部放疗降低复发率,以期提高这些患者的生存率。     

Prognostic significance of neutrophil-to lymphocyte ratio and platelet-to lymphocyte ratio in older patients with metastatic colorectal cancer

Aging is associated with a higher risk of cancer, >70% of cancer-related deaths occur in aged patients; however, this population is underrepresented in clinical trials, therefore, clinical information regarding this age group is rather limited.ObjectivesNeutrophil-to lymphocyte ratio (NLR) and platelet-to lymphocyte ratio (PLR) have been described as biomarkers in cancer, thus, we have assessed their impact in an aged cohort of patients with metastatic colorectal cancer (mCRC).Patients and Methods110 patients with a mean age of 72.2 years at diagnosis were retrospectively reviewed; NLR and PLR were calculated and dichotomized using a cutoff point estimated by a ROC curve. Survival curves and Cox regression analysis were performed to assess the prognostic potential of ratios in terms of progression free survival (PFS) and overall survival (OS).ResultsHigh NLR was associated to worse outcome in terms of PFS (ten vs sixteen months; Log rank <0.001) (HR 2.00 95%CI 1. 29–3.11; p = .002) and OS (20 vs 26 months; Log rank 0.002) (HR 2.28 95%CI 1.40–3.71; p = .001). Similarly it occurs with high PLR and PFS (nine vs fifteen months; Log rank 0.04) (HR 1.55 95%CI 1.01–2.40; p = .04) and OS (nineteen vs 25 months; Log rank <0.001) (HR 2.35 95%CI 1.45–3.80; p < .001).ConclusionThis study confirms the role of NLR and PLR as accessible and noninvasive biomarkers that could be use as a routine tool in the clinical practice in geriatric patients with mCRC.     

Lymphovascular space invasion as a prognostic determinant in uterine cancer.

The objective of this study was to evaluate the clinical significance of lymphovascular space invasion (LVSI) in patients with uterine cancer in terms of lymph node metastasis, recurrence and survival rate. A total of 190 patients with newly diagnosed uterine cancer who underwent total abdominal hysterectomy (TAH), bilateral salpingo-oophorectomy (BSO), omentectomy, peritoneal washing or ascitic fluid collection, and pelvic/paraaortic lymph node sampling at Chiang Mai University Hospital between January 1999 and December 2004 were evaluated. All medical records and histopathologic slides were retrospectively reviewed to determine the relationship between LVSI and clinicopathological characteristics. LVSI was present in 79 patients (42%) and significantly correlated with lymph node metastasis (p0.001), BMI 25 kg/m2 (p0.001), advanced FIGO stage (p 0.001), poor histologic grade (p0.001), and deep uterine invasion (p0.001). Patients with LVSI, when stratified by FIGO stage, also had a significant lower 5-year survival rate. For those who had disease recurrence, LVSI and histologic grade were found to be independent prognostic factors in a multivariate analysis. LVSI was one of the prognostic determinants for disease recurrence and associated with poor survival in patients with uterine cancer.     

中性粒细胞与淋巴细胞比值早期预测直肠癌术后吻合口瘘的价值

目的探讨中性粒细胞与淋巴细胞比值(NLR)在早期预测直肠癌术后吻合口瘘中的临床价值。方法收集2014年1月至2017年12月就诊于郑州大学附属肿瘤医院普外科、行直肠癌根治术的787例患者的临床资料。患者于术后第1、3、5天分别检测血常规,记录白细胞计数(WBC),计算NLR。分析术后第1、3、5天NLR与吻合口瘘的关系,绘制受试者工作特征(ROC)曲线,并计算曲线下面积(AUC),评价术后NLR预测吻合口瘘的准确率。结果术后第1、3、5天,吻合口瘘患者的平均WBC分别为13.2×10^9/L、9.1×10^9/L和8.9×10^9/L,吻合口愈合患者的平均WBC分别为12.9×10^9/L、9.0×10^9/L和8.8×10^9/L,差异无统计学意义(P>0.05)。术后第1天,吻合口瘘和吻合口愈合患者的平均NLR分别为13.3和11.6,差异无统计学意义(P=0.364);吻合口瘘患者术后第3、5天的平均NLR分别为10.9和7.6,吻合口愈合患者术后第3、5天的平均NLR分别为9.3和5.3,差异有统计学意义(P<0.05)。ROC曲线显示,术后第3天NLR截点值为8.6时,预测直肠癌术后吻合口瘘的灵敏度为73.2%,特异度为75.6%,AUC为0.744。术后第5天NLR截点值为5.5时,预测直肠癌术后吻合口瘘的灵敏度为69.6%,特异度为75.5%,AUC为0.726。多因素分析显示,术后第3天NLR为预测直肠癌术后吻合口瘘的独立因素。结论术后第3天NLR可以较为准确地预测直肠癌术后吻合口瘘的发生,有助于早期发现吻合口瘘,减少吻合口瘘导致的并发症。     

中性粒细胞与淋巴细胞比值及血小板与淋巴细胞比值变化在直肠癌新辅助治疗中的意义

目的探讨新辅助治疗前后中性粒细胞与淋巴细胞比值(NLR)及血小板与淋巴细胞比值(PLR)变化在直肠癌新辅助治疗中的意义。方法回顾性分析2013年11月至2015年1月山西省肿瘤医院收治的86例接受新辅助治疗的直肠癌患者资料,分析新辅助治疗前后NLR、PLR变化与患者临床病理特征及疗效的关系。结果86例患者治疗后NLR、PLR升高均为43例。直肠癌患者新辅助治疗前后的NLR及PLR变化与患者年龄、性别、TNM分期、淋巴结转移及癌结节数量、肿瘤长径均无关(均P>0.05),肿瘤与肛门距离<6 cm者治疗后NLR、PLR升高者比例均高于≥6 cm者[60.00%(30/50)比36.11%(13/36),χ^2=4.778,P=0.029;64.00%(32/50)比30.56%(11/36),χ^2=9.364,P=0.002];体质量指数≥28 kg/m2者治疗后NLR、PLR升高者比例均高于<28 kg/m2者[81.82%(9/11)比45.33%(34/75),χ^2=5.108,P=0.024;90.91%(10/11)比44.00%(33/75),χ^2=8.444,P=0.004]。治疗后NLR降低组患者的缓解率高于NLR升高组[72.09%(31/43)比51.16%(31/43),χ^2=3.983,P=0.046],而治疗前后PLR变化与患者新辅助治疗效果无关(P>0.05)。结论直肠癌患者新辅助治疗前后NLR变化与其疗效相关。