Progression-free Overall Survival Research Articles

Clinical and Hematological Predictors of High-Grade Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors

Background: Life-threatening immune-related adverse events (irAEs) that require hospital admission are not uncommon in patients treated with immune checkpoint inhibitors (ICIs). The clinical and hematological parameters are attractive biomarkers as potential predictors of irAE. Methods: This is a retrospective study of patients with melanoma and lung cancer treated with ICIs between 2015 and 2019 at the University of South Alabama Mitchell Cancer Institute. Fisher’s exact test, Pearson Chi-squared test, log-rank test, and Cox proportional hazard model were used to evaluate clinical and hematological parameters as possible predictors of irAE. Results: The cohort consisted of 160 patients treated with at least two doses of ICI, of which 54 (33.8%) patients had melanoma and 106 (66.3%) had lung cancer. Incidence of irAE did not have any bearing on the overall survival (OS) or progression-free survival (PFS) of the cohort. The clinical factors associated with irAE were dual-agent therapy (ipilimumab/nivolumab combination) and high disease burden (≥ 2 metastatic sites). The irAE-group had a lower mean platelet-to-lymphocyte ration (PLR, 200 vs. 257, P = 0.04). Although not statistically significant at the level of 0.05, other factors such as type of cancer (lung cancer > melanoma (P = 0.06)), stage at treatment (stage IV > stage II and III disease (P = 0.06)), and higher absolute lymphocyte counts (P = 0.07) showed a considerable association with irAE and warrants further review with different patient data. Conclusions: Irrespective of ICI used to treat lung cancer and melanoma, patients with high disease burden and dual-agent ICI therapy were more prone to irAE. The only hematological parameter that may predict the incidence of irAE is low baseline PLR. J Clin Med Res. 2021;13(5):268-275 doi: https://doi.org/10.14740/jocmr4511

Circular RNA circ-MTO1 serves as a novel potential diagnostic and prognostic biomarker for gallbladder cancer.

Primary gallbladder carcinoma (GBC) is one of the most common biliary malignancies in the gastrointestinal tract. In this work, we examined the roles of circular-mitochondrial translation optimization 1 (circ-MTO1) in GBC tissues and patient plasma. Circ-MTO1 expression in GBC tissues and patient plasma was evaluated by quantitative Real Time-PCR (qRT-PCR). The relationships between circ-MTO1 expression and the pathological characteristics of GBC were analyzed. Kaplan-Meier survival curve was applied to calculate overall survival (OS) and progression-free survival (PFS) in GBC patients with different circ-MTO1 expression. The univariate COX regression curve analysis method was employed to analyze the potential relationships between high circ-MTO1 expression and OS and PFS. At last, we assessed the diagnostic value of the circ-MTO1 level in GBC patient plasma. Circ-MTO1 expression was significantly upregulated in tumor tissues and plasma in GBC patients. In addition, circ-MTO1 expression was associated with clinical-pathological characteristics in GBC. High circ-MTO1 expression served as an independent prognostic factor for poor OS and PFS in GBC patients. Moreover, upregulated plasma circ-MTO1 level was significantly associated with tumor development. Circ-MTO1 is a potential early diagnostic and prognostic biomarker for patients with gallbladder cancer. Thus, our present work might provide a new understanding of the diagnosis and treatment of GBC.

Anaplastic thyroid cancer: How far can we go?

Globally, thyroid cancer accounts for 2 % of all cancer diagnoses, and can be classified as well-differentiated or undifferentiated. Currently, differentiated thyroid carcinomas have good prognoses, and can be treated with a combination of therapies, including surgical thyroidectomy, radioactive iodine therapy and hormone-based therapy. On the other hand, anaplastic thyroid carcinoma, a subtype of undifferentiated thyroid carcinoma characterized by the loss of thyroid-like phenotype and function, does not respond to either radioactive iodine or hormone therapies. In most cases, anaplastic thyroid carcinomas are diagnosed in later stages of the disease, deeming them inoperable, and showing poor response rates to systemic chemotherapy. Recently, treatment courses using multiple-target agents are being explored and clinical trials have shown very promising results, such as overall survival rates, progression-free survival and tumor shrinkage. This review is focused on thyroid carcinomas, with particular focus on anaplastic thyroid carcinoma, exploring its undifferentiated nature. Special interest will be given to the treatment approaches currently available and respective obstacles or drawbacks. Our purpose is to contribute to understand why this malignancy presents low responsiveness to current treatments, while overviewing novel therapies and clinical trials.

Intraoperative radiotherapy with low energy x-rays for primary and recurrent soft-tissue sarcomas

BackgroundSoft tissue sarcomas (STS) treatment remains a therapeutic challenge. Intraoperative radiotherapy (IORT) resembles a safe and efficient for STS treatment. The first data on electronic-IORT (eIORT) using low-energy photons is herein presented.MethodsThirty-one patients with newly and recurrent STS were retrospectively assessed. EIORT was applied with low-energy photons during surgery. The dose was either prescribed to the applicator surface (spherical applicators) or 5 mm depth (flat applicators). Overall progression-free survival (O-PFS), local progression-free survival (L-PFS), overall survival (OS) and adverse events were evaluated.ResultsMedian follow-up was 4.88 (1.0–8.95) years. Twenty-five patients (80.6%) had recurrent STS with prior treatment. The resection status was R1 in 25.8% and R2 in 6.5%. The distribution was 51.7% for extremities, 35.5% for abdomen and pelvis, 9.7% for thorax and 3.2% for head and neck tumors. The median O-PFS was 11.0 months, with 42.6% 5-year estimated O-PFS. The only local recurrence in the primary setting occurred after 22 months. Median L-PFS in recurrent STS was 12.5 months, with 65.5% 5-year estimated L-PFS. The 5-year OS estimated rate was 94.7% (3 events after 7 years). No G3 toxicity related to eIORT was observed. Two patients exhibited G2 acute neuropathic pain. Late neuropathic pain was seen in 6 patients being 3 graded as G1 and 3 as G2. No wound-related toxicity was found.ConclusionElectronic IORT with low-energy photons is a safe treatment option for STS, yielding similar outcomes as historical series reporting IORT with electrons or HDR brachytherapy.

Hyperthermic Intraperitoneal Chemotherapy for Primary or Recurrent Adrenocortical Carcinoma. A Single Center Study.

Background. This study explores the impact of Hypertermic Intra PEritoneal Chemotherapy (HIPEC) on adrenocortical carcinoma (ACC) management through a safety analysis completed by a preliminary evaluation of survival performances. Methods. Retrospective chart review of 27 patients submitted to surgical treatment completed by HIPEC for primary (SP, 13 patients) or recurrent (SR, 14 patients, 17 treatments) ACC. Safety was evaluated by means of procedural morbidity and mortality. Survival performances included multiple end points: local/peritoneal disease-free survival (l/pDFS), overall progression-free survival (OPFS), and overall survival (OS). Results. In the SP group, mortality was nil and morbidity was 46% (major 23%). At a median follow-up of 25 months, the median value for all the different survival measures had not been reached. Mortality was also nil in the SR group. However, morbidity was 77% (major 18%). Median l/pDFS and OPFS were 12 ± 4 and 8 ± 2 months, respectively. At a median follow-up of 30 months, median OS had not been reached. Conclusion. Surgery and HIPEC is an invasive procedure. Its employment in the surgery for primary setting deserves attention as it may affect oncologic outcomes positively. Its value in the management of recurrences seems less appreciable, albeit it may find its place in the multimodal management of a rare disease for which multiple therapeutic options do not yet exist.

Survival analysis and quality of life of pediatric low grade glioma treated by postoperative radiotherapy

Objective To analyze the clinical characteristics of children with low grade glioma (LGG) and evaluate their survival status and quality of life in LGG pediatric patients after postoperative radiotherapy. Methods Clinical data of 27 LGG children aged≤14 years admitted to Department of Radiation Oncology of our hospital from January 2011 to December 2017 were retrospectively analyzed. The 5-year overall survival (OS) and progression-free survival (PFS) were estimated with the Kaplan-Meier method.The quality of life was evaluated by body mass index (BMI), WeeFIM and enrollment situation. Results The 5-year OS and PFS of 27 pediatric patients were 92% and 87%. BMI was measured in 25 children who were still alive and the results showed that 1 child was slightly emaciated, 3 were overweight and 21 were normal. The total score of WeeFIM was> 108 in 21 cases and< 90 in 4 cases. In terms of social role-playing assessment, 5 cases delayed enrollment for≥ 2 years, 2 cases had good adaptation except the difficulties due to lameness, 7 of them had poor study performance, but had no communication barrier. Conclusions Children with LGG can obtain relatively excellent OS and PFS after postoperative radiotherapy. Part of the children with long-term survival may experience a declined quality of life, which is mainly manifested with a decline in motor and cognitive functions. Key words: Pediatric low grade glioma/radiotherapy; Survival; Quality of life

Single-docking transperitoneal robotic-assisted nephroureterectomy: surgical techniques and outcomes

Objective To introduce and discuss the efficacy of a new technique to perform transperitoneal single-docking robot-assisted laparoscopic nephroureterectomy (RNU). Methods A total of 44 patients diagnosed with urothelial neoplasm of the renal pelvis or were investigated from January 2016 to November 2019. RNU was performed by a single surgeon. Among the 44 patients, 31 were male, and 13 were female. The median age was 63 (IQR: 58-71). The median body mass index (BMI) was 23.08 (IQR: 21.55-24.60) kg/m2. All operations were performed with general anesthesia. The patients were positioned 80 degrees flank with the diseased side up, and the head was tilted 10 degrees downwards. The camera port was placed one finger lateral to the umbilicus. For the right-sided tumors, robotic arm 1 was inserted through the trocar on the right pararectus line, 8 cm above the umbilicus, and robotic arm 2 was inserted through the trocar on the same line, 8 cm below the umbilicus. Assistant trocar 1 was placed where the anterior midline joins the perpendicular bisector of the camera port and robotic 2, and assistant trocar 2 was placed below the xiphoid process. For the left-sided tumors, all trocars were centrosymmetric to that of the right-sided tumors, except that assistant port 2 was placed 3 finger width above the pubic symphysis. The peritoneum was incised along the Toldt line, and the inferior vena cava was isolated (for left sided tumor, the abdominal aorta was isolated instead). The renal artery and vein were clipped with Hem-o-lok and ligated, and the kidney were isolated. The ureter was identified and isolated downwards across the common iliac artery and then clipped distal to the tumor site. The bladder cuff was resected and sutured under the laparoscopy. Results The median operation time was 145 (IQR: 130-175) min, with the median console time of 119 (IQR: 108.5-136.0) min, the anastomosis of bladder cuff of 12 min, and the median estimated blood loss of 50(20-100)ml. After the surgery, 6 Clavien-Dindo grade 2 complications occurred, including 2 chylous leakage, 1 hemostasis, 1 blood transfusion, 1 deep vein thrombus, and 1 acute coronary syndrome. The median length of stay (LOS) was 8 (IQR: 6.5-10.0) d. The median length of follow-up was 12 months. In total, 5 patients were dead, including 3 cancer-specific death. Four recurrence occurred and caused 3 death. The 2-year overall survival and progression-free survival were 68.2% and 77.9%, respectively. Conclusions The technique of RNU with simultaneous bladder cuff excision (BCE). Our technique improved the surgical outcome. The perioperative complication rate was low, and the short-term survival outcomes were satisfactory. Key words: Ureteral neoplasms; Upper tract urothelial carcinoma(UTUC); Nephroureterecto-my; Robotic surgery; Laparoscopic surgery

Efficacy and safety of neoadjuvant concurrent chemoradiotherapy followed by surgery versus surgery alone in the treatment of resectable esophageal squamous cell carcinoma: a Meta-analysis

Objective To systematically evaluate the efficacy and safety between neoadjuvant concurrent chemoradiotherapy followed by surgery and surgery alone in the treatment of resectable esophageal squamous cell carcinoma. Methods Literature review was performed from Embase, PubMed, Web of Science, Cochrane Library, CBM, Wanfang Data, CNKI and Chongqing VIP. The randomized controlled clinical trials of concurrent chemoradiotherapy followed by surgery versus surgery alone in the treatment of resectable esophageal squamous cell carcinoma were retrieved. The meta-analysis of survival data, R0 resection rate, incidences of postoperative complications and peritreatment mortality was conducted by using RevMan 5.3 software. Results A total of 1450 patients from 11 controlled clinical trials were included in this meta-analysis. The results of the meta-analysis showed that concurrent chemoradiotherapy followed by surgery group had significantly higher 2-and 5-year overall survival rate (RR=1.14, 95%CI: 1.05-1.23, P=0.00) and progression-free survival rate (RR=1.56, 95%CI: 1.05-2.32, P=0.03). R0 resection rate were also improved in concurrent chemoradiotherapy followed by surgery group (RR=1.10, 95%CI: 1.05-1.14, P=0.00). Compared with the surgery alone group, the incidence of arrhythmia in the concurrent chemoradiotherapy plus surgery group was significantly higher (RR=2.45, 95%CI: 1.37-4.38, P=0.00). However, there was no significant difference in the overall incidence of postoperative complications (RR=1.12, 95%CI: 0.79-1.59, P=0.51) and incidence of peritreatment mortality (RR=1.78, 95%CI: 0.90-3.52, P=0.10) between two groups. Conclusions Neoadjuvant concurrent chemoradiotherapy followed by surgery improves the survival and R0 resection rate over surgery alone among patients with resectable esophageal squamous cell carcinoma, whereas it does not increase the risk of postoperative complications. Consequently, neoadjuvant concurrent chemoradiotherapy followed by surgery is an optimal treatment for patients with resectable esophageal squamous cell carcinoma. Key words: Esophageal neoplasm/neoadjuvant chemoradiotherapy; Esophageal neoplasm/surgery; Prognosis; Meta-analysis

MAGI1-IT1 stimulates proliferation in non-small cell lung cancer by upregulating AKT1 as a ceRNA.

This study aims to illustrate the potential role of MAGI1-IT1 in the progression of non-small cell lung cancer (NSCLC) and the underlying mechanism. The relative level of MAGI1-IT1 in normal lung tissues and NSCLC tissues was determined. Its level in NSCLC patients with different tumor sizes (<5 cm or >5 cm), metastatic statues (positive or negative), and tumor staging (stage I+II or stage III+IV) was detected as well. The prognostic potential of MAGI1-IT1 in evaluating the overall survival (OS) and progression-free survival (PFS) of NSCLC patients was assessed by the Kaplan-Meier method. In A549 and PC-9 cells, the regulatory effect of MAGI1-IT1 on the proliferative ability was examined by the cell counting kit-8 (CCK-8), colony formation, and 5-Ethynyl-2'-deoxyuridine (EdU) assay. The target miRNA of MAGI1-IT1 and the target gene binding to miRNA-512-3p were predicted using the Diana database. The interactions among MAGI1-IT1/miRNA-512-3p/AKT1 regulatory loop were tested by the Dual-luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay. At last, the rescue experiments were carried out to uncover the regulatory effect of MAGI1-IT1/AKT1 axis on NSCLC progression. MAGI1-IT1 was upregulated in NSCLC tissues. Its level was higher in NSCLC patients with larger tumor size, positive metastasis, or advanced stage. High level of MAGI1-IT1 predicted worse OS and PFS in NSCLC patients. The knockdown of MAGI1-IT1 remarkably attenuated the proliferative ability in A549 and PC-9 cells. MAGI1-IT1 could target miRNA-512-3p, and AKT1 was the target gene of miR-512-3p. The overexpression of AKT1 stimulated lung cancer cells to proliferate. Of note, the elevated proliferative rate in lung cancer cells overexpressing AKT1 was reversed by the silence of MAGI1-IT1. MAGI1-IT1 is upregulated in NSCLC tissues and cell lines, and predicts a poor prognosis in NSCLC patients. MAGI1-IT1 stimulates proliferative ability in NSCLC by upregulating the AKT1 level by binding to miRNA-512-3p.

UCHL1 enhances the malignant development of glioma via targeting GAS2.

To detect the expression pattern of UCHL1 in glioma samples and its influence on the metastasis of glioma, as well as the underlying mechanism. UCHL1 levels in 42 paired glioma tissues and paracancerous ones were detected. The relationship between UCHL1 level and pathological indexes in glioma patients was analyzed. After establishing UCHL1 knockdown model in U251 and T98-G cells, their migratory ability was assessed by transwell and wound healing assay. At last, Luciferase assay, Western blot and rescue experiments were conducted to explore the role of UCHL1 in aggravating the development of glioma through targeting GAS2. UCHL1 was upregulated in glioma samples than paracancerous ones. High level of UCHL1 indicated high rates of lymphatic metastasis and distant metastasis, as well as low rates of overall survival and progression-free survival in glioma. Knockdown of UCHL1 markedly inhibited migratory ability in glioma cells. GAS2 was the downstream gene of UCHL1. A positive correlation was found between expression levels of UCHL1 and GAS2 in glioma tissues. Overexpression of GAS2 could reverse the inhibitory effects of silenced UCHL1 on migratory ability in glioma cells. UCHL1 level is linked to lymphatic metastasis, distant metastasis and prognosis in glioma patients. It stimulates migratory ability in glioma by positively regulating GAS2 level.

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

Clinical outcomes of stereotactic body radiation therapy for T2N0M0 non-small cell lung cancer

Objective To investigate the clinical efficacy and adverse effects of stereotactic body radiotherapy (SBRT) in the treatment of T2N0M0 non-small cell lung cancer (NSCLC) patients. Methods By retrospectively analyzing the clinical data of 30 inoperable patients with stage T2N0M0 NSCLC treated by SBRT, the overall survival, progression-free survival, cancer-specific survival and adverse effects were determined. Results The median follow-up was 18.4 months. The 1-, 2-, and 3-year overall survival rates were 92.2%, 92.2% and 80.6%, respectively. The corresponding cause-specific survivals were 95.7%, 95.7% and 83.7%. The progression-free survivals were 70.2%, 54.1% and 40.6%. The local control rates were 100%, 94.4%, and 94.4%. The regional controls were 84.2%, 72.1%, and 54.1%; and distant controls were 84.6%, 72.4% and 64.3%, respectively. Twenty patients (66.7%) developed symptoms of grade 1 radiation-related toxicities: dyspnea, chest pain, fatigue, cough, esophagitis, or pneumonia. Among these, 5 patients suffered grade ≥2 radiation pneumonitis, and one patient experienced grade 4 radiation pneumonitis. Conclusions SBRT was efficient and safe for patients with inoperable T2N0M0 NSCLC, imposing tolerable toxicities. Key words: Stereotactic body radiation therapy; Non-small cell lung cancer; Overall survival; Progression-free survival; Cause-specific survival

Analysis of prognostic factors and survival status of children with medulloblastoma

Objective To investigate the prognostic factors and survival status of children with medulloblastoma (MB) by using retrospective analysis. Methods From February 2011 to December 2017, 224 children with newly-diagnosed MB were enrolled in this study, which was carried out at Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University.The overall survival (OS) rate and progression-free survival (PFS) rate were calcula-ted by using Kaplan-Meier method, the difference between 2 groups was tested by Log-rank method, and prognostic factors were analyzed by COX regression. Results Until December 30, 2018, the median survival time of all these 224 children was 4.1 years, the survival rate was 74.6%, complete response (CR) rate was 60.3%, and the relapse rate was 1.7%. The 5-year PFS rate and 5- year OS rate of all patients were (58.2±3.6)% and (72.5±3.3)%, respectively. Survival rates of children in the high-risk group, with metastatic disease, aged <3 years, and with positive tumor cells in the cerebrospinal fluid(CSF) were very low. The 5-year OS rates were (54.8±5.3)%, (57.7±5.9)%, (41.6±8.7)%, and (53.0±7.3)%, respectively.Compared to others, the children with MB large-cell/anaplastic histology [5-year OS rate was (35.3±13.6)%] and MB group 3 subtype [3-year OS rate was (25.0±13.0)%] lived a miserable life.Meanwhile, the children in the stand-risk group, without metastatic disease, no large-cell/anaplastic histology, age older than 3 years, and with tumor cell negative in CSF, lived a better life. The 5-year OS rates were (87.5±3.5)%, (80.3±3.7)%, (70.6±5.5)%, (78.3±3.3)%, and (78.4±3.5)%, respectively, and all of them were over 70.0%. No WNT tumors progressed or relapsed, and 5- year OS rate was 100.0%. The survival status of SHH subgroup was inferior to that of group 4 subtype[(64.8±5.8)% vs.(83.5±3.8)%, χ2=5.417, P=0.015]. With COX analysis, age and tumor cells in CSF at the time of diagnosis were independent risk factors for OS and PFS of MB (PFS: Wald=8.485, P=0.004; Wald=11.702, P=0.001; OS: Wald=16.274, P=0.000; Wald=7.191, P=0.007). Conclusions Survival of children with MB more than 3 years old has been reached a perfectly high level.Age and tumor cells in CSF are independent risk factors for the OS and PFS. However, the prognosis of large-cell/anaplastic histology, malignancy cell positive in CSF, group 3 and children under 3 years old, is still poor, and intensive treatment is needed urgently for those patients. Key words: Child; Medulloblastoma; Prognosis; Survival

Prognostic and survival analyses of early-stage diffuse large B-cell lymphoma of Waldeyer′s ring

Objective To analyze the clinical efficacy and prognostic factors of patients with early-stage diffuse large B-cell lymphoma of Waldeyer′s ring (WR-DLBCL) treated with CHOP-based chemotherapy. Methods A total of 137 patients diagnosed with WR-DLBCL admitted to our hospitalfrom 2006 to 2018 were enrolled, including 22 patients with stage Ⅰ and 115 patients with stage Ⅱ WR-DLBCL. All patients received CHOP-based chemotherapy, of whom 62 receiving rituximab and 87 receiving involved-field radiotherapy. The overall survival (OS), progression-free survival (PFS) and local recurrence-free survival (LRRFS) were calculated by Kaplan-Meier method. Log-rank test, was conducted for univariate analysis and Cox’s regression model was performed for multivariate analysis. Results The 5-year OS, PFS, and LRFFS in the whole group were 78.6%, 69.5% and 83.2%, and 87.5%, 80.2%, 90.9% in the comprehensive treatment group, and 64.2%, 53.6% 72.9% in the chemotherapy group, respectively. Univariate analysis showed that lactate dehydrogenase (LDH), international prognostic index score, large mass, rituximab, chemotherapy cycle and comprehensive treatment were the prognostic factors of OS and PFS. In addition, LDH, large mass and comprehensive treatment were the prognostic factors associated with LRFFS. Multivariate analysis demonstrated that LDH, comprehensive treatment mode and rituximab were the prognostic factors of OS. LDH and comprehensive treatment mode were the prognostic factors associated with PFS. LDH was a prognostic factor of LRFFS. Conclusion Patients with early-stage WR-BLBCL obtain excellent clinical prognosis. In the era of rituximab treatment, chemotherapy combined with radiotherapy remains an efficacious treatment of early-stage WR-BLBCL. Key words: Diffuse large B-cell lymphoma of Waldeyer′s ring/targeted therapy; Diffuse large B-cell lymphoma of Waldeyer′s ring/radiotherapy; Diffuse large B-cell lymphoma of Waldeyer′s ring/chemotherapy; Prognosis

Circulating tumor DNA applications in treatment monitoring of metastatic colorectal cancer patients

Colorectal cancer is the third most common cancer worldwide. New cancer treatment strategies such as monoclonal antibodies against growth factor and angiogenesis receptors improved the overall survival (OS) and progression-free survival (PFS) in metastatic colorectal cancer (mCRC) patients. However, acquired resistance could happen after these therapies. Circulating tumor DNA (ctDNA) is the DNA fraction derived from tumor cells and could be applied as a non-invasive method for detecting tumor mutations before, during, and after therapies. Here, we reviewed most of the studies on the application of ctDNA as treatment monitoring in mCRC patients who receive different target therapies. Also, we compared ctDNA with other existing cancer-treatment monitoring methods.

Effect of peripheral blood lymphocyte-to-monocyte ratio on prognosis of esophageal cancer patients treated with intensity-modulated radiotherapy

Objective To observe the variation trend of the peripheral blood lymphocyte-to-monocyte ratio (LMR) during radiotherapy in patients with esophageal cancer and analyze the relationship between LMR and the radiation-induced injury, aiming to provide parameters for accurate evaluation of radiotherapy responses and clinical efficacy. Methods Clinical data of 248 eligible patients undergoing definitive radiotherapy in our department from January 2013 to December 2015, 248 were retrospectively analyzed. The routine peripheral blood examination was performed weekly before, during and at the end of radiotherapy. The absolute number of lymphocyte and monocyte was recorded to calculate the LMR. The standard classification of LMR value was conducted based on the median value of each parameter. All data including the lesion length, lesion location, clinical stage and LMR were analyzed using the Kaplan-Meier, cox and logistic regression methods, respectively. Results LMR displayed an exponential decline during radiotherapy. Univariate analysis showed that the average LMR value was the influential factor of overall survival (P=0.011) and progression-free survival (P=0.017). The mean LMR value almost exerted significant effect upon local control rate (P=0.053). No significant correlation was observed between the mean LMR value and radioactive esophagitis and pneumonitis. Stratified analysis based on the results of multivariate analysis demonstrated that patients with higher average LMR value still had longer survival. Logistic regression model revealed that the length of esophageal lesion and irradiation pattern were the influential factors of the mean LMR value. Conclusions LMR value displays an exponential decline during radiotherapy. The greater amplitude prompts the worse prognosis. The wider the irradiation field and the greater decrease in LMR exert more obvious impact on the prognosis. Key words: Lymphocyte-to-monocyte ratio; Esophageal neoplasm/intensity-modulated radiotherapy; Prognosis

Systemic immune-inflammation index as a prognostic marker in patients with newly diagnosed metastatic nasopharyngeal carcinoma: a propensity score-matched study

Background: Systemic immune-inflammation index (SII) is significantly associated with poor survival in variety of cancers. However, SII has not yet been investigated in patients with newly diagnosed metastatic nasopharyngeal carcinoma (mNPC). Thus, our aim is to explore the role of SII in metastatic Nasopharyngeal Carcinoma. Methods: Two hundred and forty-three patients with newly diagnosed mNPC were retrospectively enrolled. The Kaplan-Meier analysis and Cox regression analysis was performed to evaluate the prognostic value of SII in overall survival (OS) and progression-free survival (PFS). Heterogeneity of factors was balanced by using propensity score-matched (PSM) analysis (1:1 for high SII versus low SII). Results: Kaplan-Meier analysis showed that patients with high SII were associated with poor median OS (18.0 vs. 36.0 m, P Conclusions: SII is an independent prognostic biomarker for poor OS and PFS in patients with newly diagnosed mNPC and might be a promising tool for guiding treatment strategy decisions.

Expression level of ZNF217 in bladder cancer and its clinical significance

Objective To determine the expression of ZNF217 protein in bladder cancer tissues and to analyze its clinicopathological characteristics, so as to clarify its clinical significance. Methods The clinicopathological data of 123 patients with bladder cancer who underwent bladder cancer resection were retrospectively analyzed. The expression of ZNF217 protein in bladder cancer tissues and corresponding adjacent tissues was detected by immunohistochemistry, and its correlation with clinical characteristics of patients was analyzed. Results ZNF217 protein was highly expressed in tumor tissues, and the ratio of high expression of tumor tissues was 67.4%, but it was lowly expressed in adjacent tissues. By comparing with clinicopathological features, the expression level of ZNF217 was significantly correlated with tumor T stage and tumor recurrence (all P 0.05). The survival analysis showed that patients with high expression of ZNF217 in bladder cancer had significantly shorter overall survival and progression-free survival than those with low ZNF217 expression (all P<0.05). Conclusions ZNF217 is highly expressed in bladder cancer tissues, and its expression level is associated with tumor stage, tumor recurrence and poor prognosis, suggesting that it can be used as a potential therapeutic target for bladder cancer. Key words: Bladder cancer; Immunohistochemistry; ZNF217; Tumor stage; Recurrence

The role of radiotherapy in primary central nervous system lymphoma

Objective To explore the role of radiotherapy in the treatment of primary central nervous system lymphoma. Methods Clinical data of 60 patients diagnosed with primary central nervous system lymphoma from September 2010 to December 2017 were retrospectively analyzed. Among them, 50 cases were diagnosed by histopathological examination after stereotactic biopsy or tumor resection and 10 patients were diagnosed by gadolinium enhanced magnetic resonance imaging (MRI). Fifty-two patients underwent chemotherapy, and 45 of them received methotrexate-based chemotherapy, 25 received rituximab-based regimen. Twenty-seven patients were given with planned whole brain radiotherapy, while 33 patients were not. Salvage radiotherapy was delivered in 9 patients after treatment failure. Results The median follow-up time was 28 months (5-70 months). The median overall survival time and median progression-free survival time of the whole patients was 22 months (5-65 months) and 13 months (5-55 months), respectively. The 4-year overall survival rate and progression-free survival rate were 61% and 33%, respectively. The 4-year overall survival rates between patients with and without planned whole brain radiotherapy were 68% and 54%(P=0.083). The 4-year progression-free survival rates between patients with and without planned whole brain radiotherapy were 47% and 20%(P=0.014), respectively. Patients with and without salvage whole brain radiotherapy had a 4-year overall survival of 49% and 68%, respectively (P=0.398). Among patients who received whole brain radiotherapy, patients with a lower dose of ≤36 Gy had a similar overall survival compared with those with a higher dose of>36 Gy (80% vs. 45%, P=0.136). Conclusions Radiotherapy is part of the comprehensive treatment of primary central nervous system lymphoma. Planned radiotherapy may bring clinical benefits to patients during the comprehensive therapy. However, the irradiation dose to the whole brain should not be too high because of neurotoxicity. Key words: Primary central nervous system lymphoma/radiotherapy; Primary central nervous system lymphoma/chemotherapy; Prognosis

The efficacy and safety of neoadjuvant therapy followed by radical surgery versus definite chemoradiotherapy in the treatment of IB2-IIB cervical cancer: a meta-analysis

Objective To systematically evaluate the efficacy and safety between neoadjuvant therapy followed by radical surgery and definite chemoradiotherapy in the treatment of ⅠB2-ⅡB cervical cancer. Methods A computerized search was performed in PubMed, Embase, Cochrane Library, Web of Science, CBM, Wanfang Data, CNKI and VIP to collect controlled clinical trials related to neoadjuvant therapy followed by radical surgery versus definite chemoradiotherapy in the treatment of ⅠB2-ⅡB cervical cancer. The meta-analysis of survival data and adverse events was performed by Review Manager 5.3 software. Results Nine controlled clinical trials involving 3 914 patients were included in this meta-analysis. There were no significant differences in overall survival (HR=0.83, P=0.31) and progression-free survival (HR=0.85, P=0.57) between two groups. Compared with patients receiving definite chemoradiotherapy, those in the neoadjuvant therapy group had a significantly lower risk of irradiation enteritis (RR=0.27, P=0.03), whereas no significant difference was observed in the risk of irradiation cystitis (RR=0.30, P=0.34) and grade ≥3 neutropenia (RR=0.77, P=0.46) between two groups. Conclusion In the treatment of locally advancedⅠB2-ⅡB cervical cancer, two modalities show similar survival benefits. Although the neoadjuvant therapy group yields a lower incidence of irradiation enteritis, the incidence rates of irradiation cystitis and grade ≥3 neutropenia do not significantly differ between two groups. Neoadjuvant therapy followed by radical surgery is not superior to the standard therapeutic regime. Key words: Cervical neoplasm/surgery; Cervical neoplasm/concurrent radiochemotherapy; Prognosis; Meta-analysis