Three-year Survival Rates Research Articles

EMPIRE-1: Randomized Trial Comparing Conventional- vs Conventional Plus Fluciclovine (18F) PET/CT Imaging-Guided Post-Prostatectomy Radiotherapy for Prostate Cancer

Background: Molecular imaging is increasingly used to guide prostate cancer decisions and treatment planning. The specific aim was to evaluate the role of fluciclovine (18F) PET/CT [PET] in improving cancer control over conventional imaging for post-prostatectomy radiotherapy. Methods: Patients with prostate cancer with detectable PSA post-prostatectomy and negative conventional imaging were randomized to radiotherapy directed by conventional imaging (Arm 1) vs conventional imaging+PET (Arm 2). The treatment setting was an academic medical center with community affiliates. In Arm 2, radiotherapy decisions were rigidly determined by PET, which was also used for target delineation. Using a standard post-radiotherapy failure definition, failure rates at 3 years (primary study endpoint) were compared. Univariate and multivariable analyses were performed for demographic, disease, and treatment factors. Secondary endpoints included provider-reported gastrointestinal and genitourinary toxicities. Findings: From September 18, 2012 to March 4, 2019, 165 patients were randomized. PET findings resulted in a 35·4% rate of decision changes, including 4 patients having radiotherapy aborted. Median follow-up was 3·52 years. Three-year failure-free survival rate for Arm 1 vs Arm 2 was 63·0 vs 75·5% (difference,12·5; 95% CI:4·3-20·8; p=0·0028) and at 4-years was 51·2 vs 75·5% (difference,24·3; 95% CI:15·6-33·0; p<0·0001). On univariate analysis, Arm achieved a statistical trend(p=0·0540); Gleason sum, extracapsular extension, seminal vesicle invasion, pelvic field, and PSA reached significance. On multivariable analysis, Arm (HR=2·04[95%CI: 1·06-3·93], p=0·0327), extracapsular extension, pelvic field, and PSA reached significance. Toxicity was similar in both Arms. Interpretation: Inclusion of fluciclovine (18F) PET into post-prostatectomy radiotherapy decisions and planning resulted in a significant improvement in failure rate. Integration of novel PET radiotracers into radiotherapy decisions and planning for prostate cancer patients warrants further study. Trial Registration: Enrollment was done under ClinicalTrials.gov registration (NCT 01666808) which is closed to new participants. Funding: NIH R01 CA169188 [major source]; Blue Earth Diagnostics, Ltd. [cassette arrangement with Emory]. Declaration of Interests: ABJ reports personal fees from Blue Earth Diagnostics, Ltd. in the role of advisory board service outside the submitted work. ES - none. SG - none. RH - none. BH - none. PJR - none. JWS - none. PRP - none. KMX - none. MG discloses he is entitled to a royalty derived from sale of products related to the research described in this manuscript. The terms of this arrangement have been reviewed and approved by Emory University in accordance with its conflict of interest policies. For human research studies the consent forms it is stated that he is entitled to a share of sales royalty received by the University from Nihon under that agreement. The terms of this arrangement have been reviewed and approved by the University in accordance with its conflict of interest policies. VAM - none. SSJ - none. OK - none. BCC - none. MAB - none. OAA - none. AAA - none. VRD - none. DMS participates through the Emory Office of Sponsored Projects in sponsored grants including those funded or partially funded by Blue Earth Diagnostics, Ltd; Nihon MediPhysics Co, Ltd.; Telix Pharmaceuticals (US) Inc.; Advanced Accelerator Applications; FUJIFILM Pharmaceuticals U.S.A., Inc; Amgen Inc. Also reports consultant fees outside the submitted work from: Syncona; AIM Specialty Health; Global Medical Solutions Taiwan; Progenics Pharmaceuticals, Inc. Ethics Approval Statement: Signed informed consent was obtained from every trial participant. The treatment setting was at Winship Cancer Center of Emory University (academic medical center with community affiliates); institution review board approval was through Emory University.

Role of Preoperative Chemoradiotherapy in Clinical Stage II/III Rectal Cancer Patients Undergoing Total Mesorectal Excision: A Retrospective Propensity Score Analysis.

BackgroundAlthough the current standard preoperative chemoradiotherapy (PCRT) for stage II/III rectal cancer decreases the risk of local recurrence, it does not improve survival and increases the likelihood of preoperative overtreatment, especially in patients without circumferential resection margin (CRM) involvement.MethodsStage II/III rectal cancer without CRM involvement and lateral lymph node metastasis was radiologically defined by preoperative magnetic resonance imaging (MRI). Patients who received PCRT followed by total mesorectal excision (TME) (PCRT group) and upfront surgery (US) with TME (US group) between 2010 and 2016 were analyzed. We derived cohorts of PCRT group versus US group using propensity-score matching for stage, age, and distance from the anal verge. Three-year relapse-free survival rate, disease-free survival (DFS), and overall survival (OS) were compared between the two groups.ResultsA total of 202 patients were analyzed after propensity score matching. There were no differences in baseline characteristics. The median follow-up duration was 62 months (interquartile range, 46–87). There was no difference in the 3-year disease-free survival rate between the PCRT and US groups (83 vs. 88%, respectively; p=0.326). Likewise, there was no significant difference in the 3-year OS (89 vs. 91%, respectively; p=0.466). The 3-year locoregional recurrence rates (3 vs. 2% with US, p=0.667) and distant metastasis rates (16 vs. 11%, p=0.428) were not significantly different between the two groups. Time to completion of curative treatment was significantly shorter in the US group (132 days) than in the PCRT group (225 days) (p<0.001).ConclusionUsing MRI-guided selection for better risk stratification, US without neoadjuvant therapy can be considered in early stage patients with good prognosis. PCRT may not be required for all stage II/III rectal cancer patients, especially for the MRI-proven intermediate-risk group (cT1-2/N1, cT3N0) without CRM involvement and lateral lymph node metastasis. Further prospective studies are warranted.

Early Administration of Tolvaptan Can Improve Survival in Patients with Cirrhotic Ascites.

(1) Backgrounds and aim: Tolvaptan, a selective vasopressin type 2 receptor antagonist, was approved for ascites, and its short-term efficacy and safety have been confirmed. However, it is still unclear whether this novel drug may improve long-term survival rates in cirrhotic patients with ascites. (2) Patients and methods: A total of 206 patients who responded insufficiently to conventional diuretics and were hospitalized for refractory ascites for the first time were retrospectively enrolled in this study. Among them, the first 57 consecutive patients were treated with conventional diuretics (the conventional therapy group); the latter 149 consecutive patients were treated with tolvaptan in addition to the conventional therapy (the tolvaptan group). (3) Results: The exacerbation of renal function was significantly milder in the tolvaptan group than in the conventional therapy group. The prognostic factors for survival in the tolvaptan group were being male, having hyperbilirubinemia, having a high blood urea nitrogen (BUN), and receiving high-dose furosemide at the start of tolvaptan treatment. The one-year and three-year cumulative survival rates were 67.8 and 45.3%, respectively, in patients with low-dose furosemide (<40 mg/day) at the start of tolvaptan treatment. The prognosis was significantly better in the tolvaptan group with low-dose furosemide than in the conventional therapy group (p < 0.001). (4) Conclusion: Tolvaptan can improve survival in patients with cirrhotic ascites, especially when tolvaptan is started before high-dose furosemide administration.

Outcome of chemoradiotherapy using intensity-modulated radiation therapy for cervical esophageal cancer: a single institute experience.

The role of intensity-modulated radiation therapy in the treatment of cervical esophageal cancer remains unclear. The outcome of concurrent chemoradiotherapy for cervical esophageal squamous cell carcinoma using intensity-modulated radiation therapy was retrospectively evaluated. Between 2004 and 2017, 36 patients with cervical esophageal cancer treated with intensity-modulated radiation therapy were included. Among these patients, one had stage II disease, three stage III, 19 stage IVA, and 13 stage IVB. All patients received radiotherapy at a dose of 60Gy and concurrent platinum-based doublet chemotherapy. The median follow-up period for surviving patients was 36months. Three-year locoregional control, progression-free survival, and overall survival rates were 54, 40, and 46%, respectively. Disease progression was noted in 20 out of 36 patients (56%). Grade 3 late toxicities were observed in four patients (three esophageal stenoses and one carotid artery stenosis). There were no grade 4-5 toxicities. Univariate analysis identified the duration of radiotherapy as a prognostic factor for overall survival. Chemoradiotherapy using intensity-modulated radiation therapy for locally advanced cervical esophageal carcinoma achieved satisfactory locoregional control and survival with acceptable toxicities.

Metastasis to lymph nodes around the vascular tie worsens long-term oncological outcomes following complete mesocolic excision and conventional colectomy for right-sided colon cancer.

Oncologic outcomes after complete mesocolic excision (CME) in colon cancer are under investigation. The aim of our study was to compare CME and conventional colectomy (CC) in terms of pathological and oncological outcomes for right colon cancer and to evaluate the impact of lymph node metastasis around the vascular tie on survival. Consecutive patients with right colon cancer who had CME or CC between January 2011 and August 2018 at two specialized centers in Turkey were included. Statistical analyses were performed with respect to demographic characteristics, operative and pathologic outcomes, harvested and metastatic lymph nodes around the vascular tie (LNVT), recurrences, and survival. There were 91 patients in the CME group (58 males, mean age 64 ± 16years) and 192 patients in the CC group (96 males, mean age 66 ± 14years). The mean number of harvested lymph nodes (CME: 42 ± 15 vs CC: 34 ± 13, p = 0.01) and LNVT were higher in the CME group (CME: 3.2 ± 2.2 vs CC: 2.4 ± 1.6, p = 0.001). LNVT metastases were 7.7% and 8.3% in the CME and CC groups, respectively (p = 0.85). Three-year overall and disease-free survival rates were 96.4% and 90.9% in the CME group and 90.4% and 87.6% in the CC group in stage I-III patients (p > 0.05). In stage III patients, the 3-year overall survival (92.5% vs 63.5%, p = 0.03) and disease-free survival (85.6% vs 52.1%, p = 0.008) were significantly better in LNVT-negative patients than in LNVT-positive patients. LNVT metastasis seems to be the key factor associated with poor disease-free and overall survival in right colon cancer regardless of the radicality of surgery.

RNA-binding proteins RBM-HuR, RBM3 and PODXL expression in urothelial carcinoma of the urinary bladder. Prognostic and clinical implications.

Aim of the studyThe clinical significance and predictive and prognostic value of HuR, RBM3, and PODXL expression in patients with urothelial bladder cancer (UBC) are not clear yet. The aim of this study was to assess HuR, RBM3 and PODXL expression in muscle invasive and non-muscle invasive UBC tissues, and to investigate the clinicopathological correlations and their predictive and prognostic impact in patients with such type of cancer.Material and methodsRBM-HuR, RBM3 and PODXL expression levels were evaluated in 70 patients with urothelial carcinoma by immunohistochemistry. The relationships between their expression, clinicopathological findings and prognostic data were analyzed.ResultsHigh RBM-HuR expression was related to muscle invasion (p = 0.008), metastasis to lymph nodes (p = 0.007), and presence of blood spread (p = 0.049). High RBM3 expression was associated with lower grade (p = 0.044), absence of distant metastasis (p = 0.025), and absence of lymph node metastasis (p = 0.018). High PODXL expression was significantly associated with advanced tumor stage (p < 0.001), larger tumor size (p = 0.050), lymphovascular invasion (p = 0.006), lymph node metastasis (p = 0.008), higher grade (p = 0.043) and distant metastasis (p = 0.002).Three-year overall survival rate was negatively associated with high expression of both RBM-HuR and PODXL while it was directly correlated with high expression of RBM3 (p = 0.008, 0.009 and 0.015 respectively). High RBM-HuR and PODXL expression and low expression of RBM3 were related to tumor recurrence (p = 0.022, 0.011 and 0.015).ConclusionsRBM-HuR and PODXL expressions are markers of poor prognosis while RBM3 is a good prognostic marker for urothelial carcinoma of the bladder.

Impact of Variant Histology on Clinical and Pathological Outcomes in Patients with the Upper Urinary Tract Urothelial Carcinoma.

ObjectivesThe objective of the study was to determine the effect of variant histology on pathological outcomes and survival in patients operated for the upper urinary tract urothelial carcinoma (UTUC).MethodsData of 128 patients who were operated for UTUC between 2001 and 2019 were retrospectively analyzed. Patients with pure urothelial carcinoma and patients with variant histology were compared in terms of demographics, pathological outcomes, and survival.ResultsThe mean age of the patients was 65±11 years, female to male ratio was 30/98 and median follow-up period was 26.5 (1–176) months. Variant histology was detected in 14.8% of patients. Variant histology was found to be associated with surgical margin positivity, lymph node metastasis, presence of lymphovascular invasion, high tumor stage and grade (p=0.001, p=0.012, p=0.001, p=0.002, and p=0.009, respectively). Three-year cancer-specific and overall survival rates were 79.6% and 77.3%, respectively. There was no statistically significant relationship between variant histology with cancer-specific and overall survival (p=0.514 and p=0.515, respectively).ConclusionVariant histology of UTUC was found to be associated with locally advanced disease, but its effect on survival could not be demonstrated.

Prognostic and clinicopathological implications of expression of Beclin-1 and hypoxia-inducible factor 1α in serous ovarian carcinoma: an immunohistochemical study.

Serous ovarian carcinoma (SOC) is anovarian cancer with ahigh fatality rate. Therefore, alot ofresearchers have tried to identify novel prognostic biomarkers which might improve thepatient prognosis. The aims ofthestudy were to detect thetissue protein expression ofBeclin-1 in addition to HIF-1α in SOC patients, to evaluate therelationship between their expression, theclinicopathological parameters, patients' prognosis, and therelation to chemotherapy resistance in SOC. We evaluated theexpression ofBeclin-1 in addition to HIF-1α in 60 patients with SOC using immunohistochemistry, followed all patients for about 36 months, analyzed associations between both markers' expression, clinicopathological data, and patients' prognosis. Beclin-1 expression was related to low grade (p=0.002), early SOC stage, absence ofperitoneal spread (p=0.006), and absence oflymph nodes, and distant metastases (p=0.004 and<0.001 respectively), while HIF-1α expression was associated with higher grade and stage (p=0.007), and presence ofnodal and distant metastases (p<0.001 and=0.012 respectively). High Beclin-1 expression and low HIF-1α expression were positively associated with good response to chemotherapy (p=0.047 and p=0.022 respectively), alower recurrence rate after successful therapy (p=0.006 and<0.001 respectively), and increased three-year recurrence-free and overall survival rates (p<0.001). In SOC patients; Beclin-1 is agood prognostic marker, while HIF-1α is apoor prognostic marker.

Circular RNA Hsa_circRNA_101996 promotes the development of Gastric Cancer via Upregulating Matrix Metalloproteinases-2/Matrix Metalloproteinases-9 through MicroRNA-143/Ten-eleven translocation-2 Pathway.

Background: The long-term survival rate of gastric cancer (GC) patients at advanced stages remains low worldwide. Circular RNAs (circRNAs) a newly studied type of non-coding RNA that play an important role in the pathogenesis and diagnosis of various diseases. In this research, we aimed to explore the functions of hsa_circRNA_101996 in GC cells and an animal model of GC.Methods: The expression of hsa_circRNA_101996, microRNA (miR)-143, and ten-eleven translocation (TET)-2 in GC tissues, the adjacent tissues, and cell lines were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Transwell assays were used to analyze the knockdown effects of hsa_circRNA_101996, miR-143, and overexpression of TET2 on cell proliferation, migration, and invasion abilities. Western blotting was used to analyze the expression of matrix metalloproteinases (MMP)2/MMP9. Binding interactions between, hsa_circRNA_101996 and miR-143 and between, miR-143 and TET2 were detected by Dual-luciferase reporter assays. Levels of protein expression were analyzed by Western blotting. Tumor models were established by subcutaneous injection of tumor cells in Bl6/Rag2/GammaC double knockout mice.Results: The result showed that hsa_circRNA_101996 expression was significantly upregulated in GC tissues compared to that in the adjacent tissues, and its level in cancer tissue was correlated with tumor size, lymphatic metastasis, and distant metastasis. Compared with the low hsa_circRNA_101996 expression group, the three-year survival rate of patients in the high hsa_circRNA_101996 expression group was significantly lower. The knockdown of hsa_circRNA_101996 dramatically suppressed the cell migration, invasion, and proliferation of GC cells by sponging to absorb miR-143 and elevated the expression of TET2. In vivo studies showed that the knockdown of hsa_circRNA_101996 delayed tumor growth. Furthermore, we revealed that TET2 regulates MMP2/MMP9 expression through the DNA demethylation pathway.Conclusion: Our findings indicate that hsa_circRNA_101996 promotes GC development by upregulating MMP2/MMP9 through miR-143/TET2 pathway, which may provide a novel target for GC.

Clinical and epidemiological aspect of malignant neoplasm of conjunctiva in the Chelyabinsk region

Malignant neoplasms of conjunctiva (MNC) are characterized by high degree of malignancy and predisposed to invasive growth and generalization of the process, which leads to fatal outcomes. Purpose: to investigate clinical and epidemiological aspects of malignant conjunctival tumors over a 18-year period starting in 2001. Material and methods. We analyzed the epidemiological factors of MNC in 51 patients aged 15 to 97 (average 63.1 ± 17.3), who were treated in the Center of Oncological ophthalmology at the Chelyabinsk regional clinical center of oncology and nuclear medicine. Results. The structure and morbidity changes of MNC are presented, showing the age and gender distribution of patients and revealing the clinical picture for varying types of the pathology. Long-term results were as follows: MNC relapses occurred in 11 patients (22.4 %) 36.0 ± 24.5 months after treatment. Tumor metastases into regional lymph nodes and hematogenous metastases averagely developed after 18.5 ± 6.8 years. Between 2008 and 2015, 9 patients (17.6 %) died. The Cancer Register of the Center was used to calculate the parameters of corrected cumulative survival rate for Chelyabinsk region population after MNC as a whole, as well as separately for melanomas and squamous cell carcinomas of the conjunctiva, and for the stages of the disease. The three-year survival rate for MNC was 80.5 %, for conjunctival melanoma 90.1 %, for squamous cell carcinomas 80.5 %. The 5-year survival rates were, respectively, 71.5, 80.1 and 60.5 %. The 3-year MNC survival rate for stages I and II of MNC was 100 %. For stage III, it was 76.9 %, and for stage IV, 33.3 %. The 5-year survival rates for stages I to IV of MNC were respectively, 100, 88.9, 69.2 % and 33.3 %. Conclusion. The new Center for oncological ophthalmology established within a multidisciplinary oncological treatment and prophylactic institution improved medical assistance and diagnostics of patients with MNP. The results obtained should be taken into account when developing preventive measures for the early detection of conjunctival malignancy.

Bone marrow transplantation from HLA-identical siblings as treatment for myelodysplasia

AbstractAllogeneic hematopoietic stem cell transplantation is the only curative therapy for myelodysplasia (MDS). To identify factors influencing transplantation outcome, we studied 452 recipients of HLA-identical sibling transplants for MDS from 1989 to 1997, reported to the International Bone Marrow Transplant Registry. Patients with treatment-related MDS or unclassified MDS were excluded. Median age was 38 years (range, 2-64 years). Sixty percent had refractory anemia with excess blasts (n = 136) or with excess blasts in transformation (n = 136). Conditioning regimens included total body irradiation in 199 (44%) cases. Marrow was T-cell depleted for 58 (13%) transplants. Cumulative incidences of neutrophil engraftment, grades II-IV acute graft-versus-host disease (GVHD), and chronic GVHD were 91% (95% confidence interval [CI], 88%-93%), 36% (95% CI, 31%-40%), and 39% (95% CI, 33%-44%), respectively. Three-year transplantation-related mortality (TRM), relapse, disease-free survival, and overall survival rates were 37% (95% CI, 32%-42%), 23% (95% CI, 19%-27%), 40% (95% CI, 36%-45%), and 42% (95% CI, 37%-47%), respectively. Multivariate analyses showed that young age and platelet counts higher than 100 × 109/L at transplantation were associated with lower TRM and higher disease-free and overall survival rates. Relapse incidence was higher in patients with high percentages of blasts in the marrow at transplantation or presentation, with high International Prognostic Scoring System scores at diagnosis, and with T-cell–depleted transplants. These findings indicate that transplantation from an HLA-identical sibling offers the possibility of long-term, disease-free survival to patients with MDS. Best candidates are younger patients with a low percentage of blasts and preserved platelet counts.

Primary bone sarcomas in KSA: A Saudi tumor registry review

ObjectivesThe geographical incidence of tumours is usually influenced by the environment, race, and culture. This study aimed to report the incidence and differences in tumour type, site of origin, and mortality across gender, regions, age, and the different characteristics of tumour types. MethodsThis retrospective cohort study included all patients diagnosed with primary bone sarcomas from January 1, 2013, to December 31, 2017. Frequencies and percentages were generated for categorical variables. Means and standard deviations were calculated for quantitative variables. A chi-squared test was used to detect differences among categorical variables. Student-t, ANOVA, and Tukey tests were used to detect differences among quantitative variables. Lastly, we calculated the incidence of each tumour type. ResultsOf 451 patients, 248 (55%) had osteosarcomas; 160 (35.5%) had Ewing's sarcoma, and 43 (9.5%) had chondrosarcoma. The incidence was 1.56 cases per 1,000,000 per year for osteosarcoma, 0.95 cases per 1,000,000 per year for Ewing's sarcoma, and 0.27 cases per million per year for chondrosarcoma. The three-year survival rate was 82.30%. Significant differences in tumour type, origin site, and three-year survival across age and gender were detected. Similarly, significant differences were also noted in origin site, grade, basis of diagnosis, and lateralisation across tumour types. ConclusionsIn our study, the observed bone sarcoma incidence rates were lower than the ones reported worldwide. Understanding the pattern of tumour behaviour in the region will help develop a risk and response-based treatment plan for early decision-making.

Pretherapeutic nutritional/inflammatory factors as predictors for survival of both early and advanced staged head and neck cancer patients

ObjectivesMalnutrition and inflammation are common in patients with head and neck cancer and are closely associated with prognosis. Although several parameters for evaluating nutritional/inflammatory status have been assessed in relation to the prognosis of patients with head and neck cancer, previous studies primarily included patients with advanced-stage disease. To date, there is no consensus regarding the most reliable parameter for predicting the prognosis of early and advanced-stage head and neck cancer. This study sought to evaluate nutritional/inflammatory prognostic factors before treatment in patients with early and advanced-stage head and neck cancer. MethodsWe retrospectively reviewed medical records of patients treated between 2008 and 2015 at our institution in order to evaluate the effects of nutritional/inflammatory parameters, including C-reactive protein/albumin ratio, modified Glasgow prognostic score, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and Geriatric Nutritional Risk Index, on overall survival. Effects of potential risk factors on overall survival were analyzed by computing Kaplan-Meier estimates; curves were compared using the log-rank test. ResultsA total of 164 patients were enrolled. C-reactive protein/albumin ratio, modified Glasgow prognostic score, platelet/lymphocyte ratio, and Geriatric Nutritional Risk Index were found to be statistically significantly correlated with overall survival. Only the Geriatric Nutritional Risk Index remained statistically significant in the multivariate analysis. The three-year survival rates according to the four-group Geriatric Nutritional Risk Index scores for normal, low, moderate, and high risk were 95.5%, 84.3%, 53.8%, and 23.4%, respectively. ConclusionThe Geriatric Nutritional Risk Index is therefore a useful prognostic factor for patients with early and advanced-stage head and neck cancer.

Immune-Related Four-lncRNA Signature for Patients with Cervical Cancer

Cervical cancer (CC) is a common gynecological malignancy for which prognostic and therapeutic biomarkers are urgently needed. The signature based on immune-related lncRNAs (IRLs) of CC has never been reported. This study is aimed at establishing an IRL signature for patients with CC. A cohort of 326 CC and 21 normal tissue samples with corresponding clinical information was included in this study. Twenty-eight IRLs were collected according to the Pearson correlation analysis between the immune score and lncRNA expression (p < 0.01). Four IRLs (BZRAP1-AS1, EMX2OS, ZNF667-AS1, and CTC-429P9.1) with the most significant prognostic values (p < 0.05) were identified which demonstrated an ability to stratify patients into the low-risk and high-risk groups by developing a risk score model. It was observed that patients in the low-risk group showed longer overall survival (OS) than those in the high-risk group in the training set, valid set, and total set. The area under the curve (AUC) of the receiver operating characteristic curve (ROC curve) for the four-IRL signature in predicting the one-, two-, and three-year survival rates was larger than 0.65. In addition, the low-risk and high-risk groups displayed different immune statuses in GSEA. These IRLs were also significantly correlated with immune cell infiltration. Our results showed that the IRL signature had a prognostic value for CC. Meanwhile, the specific mechanisms of the four IRLs in the development of CC were ascertained preliminarily.

Prognostic and Predictive Value of an Immunoscore Signature in Glioblastoma Multiform.

BackgroundAlthough increasing evidence shows that immune infiltration plays an essential role in glioblastoma (GBM), current prognostic indicators do not accurately represent the risk of immune cells infiltration in patients. It is therefore critical to identify new prognostic markers for GBM. Here, we investigated the effectiveness of using immunoscore to improve risk stratification and prediction of prognosis in GBM patients receiving chemotherapy.MethodsUsing mRNA microarrays and CIBERSORT, we analyzed 22 types of immune cell fractions in 517 GBM samples and characterized an immunoscore using the least absolute shrinkage and selection operator (LASSO) Cox regression model based on the fraction of immune cell types and patients’ overall survival. The prognostic and predictive accuracy of immunoscore was verified in the validation cohort and the entire cohort.ResultsUsing the LASSO model, an immunoscore was developed to classify patients into High and Low immunoscore groups in the training cohort (P < 0.0001) based on the fraction of eight immune cell types. The immunoscore performance was validated in the validation cohort (P < 0.0001) and the entire cohort (P < 0.0001). Furthermore, a nomogram comprising age, IDH1 status, and immunoscore was generated to predict one- and three-year survival rates in the training cohort. The predictive value of the immunoscore was also confirmed in the validation cohort and the entire cohort (C-index: 0.66, 0.67, and 0.68, respectively). In addition, we concluded that patients in the low-immunoscore group may benefit from adjuvant chemotherapy for GBM.ConclusionImmunoscore, an immune-infiltration-based signature, is a reliable prognostic and predictive tool for GBM.

RADT-44. STEREOTATIC RADIOSURGERY FOR RESIDUAL LESIONS OF PINEAL NON-GERMINOMATOUS GERM CELL TUMORS AFTER CONVENTIONAL RADIOTHERAPY: A RETROSPECTIVE STUDY

Abstract OBJECTIVE To evaluate the safety and efficacy of stereotatic radiosurgery (SRS) in treating residual lesions of pineal non-germinomatous germ cell tumors (NGGCTs) after conventional radiotherapy. METHODS The patients admitted to Guangdong Sanjiu Brain Hospital from 1 January 2008 to 31 December 2018 who diagnosed with pineal NGGCTs pathologically or clinically were retrospectively analyzed. Among those, the patients received conventional radiotherapy with or without SRS were included. The residual lesions after radiotherapy were defined with a maximum diameter &amp;gt; 10mm. Prognosis related parameters such as local control rate, progress-free survival, overall survival and treatment-related toxicity were determined. RESULTS The median follow-up time was 34 months (range 8-142 months). The objective response rate and disease control rate were 71.4% and 95.2%, respectively. Three-year progression-free survival rate was 85.2% and 3-year total survival rate was 88.0%. The univariate analysis revealed that both age and concurrent chemotherapy were not correlated with the prognosis (P=0.286, 0.824). Partial tumor resection before radiotherapy and chemotherapy, AFP＞500ng/ml, and no more than 4 cycles of adjuvant chemotherapy were poor prognostic factors (P=0.037, 0.010, 0.006). Moreover, no acute radiation response was observed after treatment with SRS. Only 1 out of 27 patients (3.7%) had brain neurotoxicity related to a prolonged course of radiochemotherapy. CONCLUSION SRS for residual lesions of NGGCTs following conventional radiotherapy appears to be well tolerant and improved local control. However, the combination of conventional radiotherapy and SRS warrants further investigations in a large-scale randomized controlled clinical trials.

Long-Term Follow-up of the Combination of Low-Intensity Chemotherapy Plus Inotuzumab Ozogamicin with or without Blinatumomab in Patients with Relapsed-Refractory Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia: A Phase 2 Trial

Long-Term Follow-up of the Combination of Low-Intensity Chemotherapy Plus Inotuzumab Ozogamicin with or without Blinatumomab in Patients with Relapsed-Refractory Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia: A Phase 2 Trial

The Important Factor in Local Control of Bone Metastatic Lesions in Radiotherapy

With the advance of systemic therapy, long-term survivors have increased and long-term local control of bone metastases are required for some of patients. The purpose of this study was to search for factors affecting local control of bone metastatic lesions in external-beam radiotherapy (EBRT). Between January 2010 and December 2019, 361 osteolytic bone metastases (spinal column, 192; pelvis, 87; rib/sternum, 35; extremity, 41; facial, 6) in 257 patients received EBRT. Local control was evaluated by follow-up CT. Doses of EBRT were 8-50 Gy (median 30 Gy). One and three-year overall survival rates were 59% and 33%, respectively. One and three-year control rates at EBRT sites were 78% and 67%, respectively. Local recurrence was observed in 18% (64 lesions) and the time of recurrence were 0.5-105 months (median 3 months). Male, age of > 70, rib/sternum and facial bone metastases, bone metastases from hepatobiliary/pancreatic/colorectal carcinoma, extraosseous invasion, EBRT ≤ 20 Gy, no use of bisphosphonates/receptor activator of NF-κB ligand (RANKL) formulation, and no use of systemic therapy after EBRT were statically significant unfavorable factors for local control (p = 0.0155,0.0005, <0.0001, <0.0001, 0.0361, 0.0010, <0.0001, and 0.0008, respectively). In multivariate analysis, age of > 70, rib/sternum/facial bone metastases, bone metastases from hepatobiliary/pancreatic/colorectal carcinoma, EBRT ≤ 20 Gy, and no use of bisphosphonates/RANKL formulation were significant unfavorable factor for local control (p = 0.0001, <0.0001, 0.0006, 0.0010, and 0.0349, respectively). For patients who can expect long-term survival, the use of bisphosphonates/RANKL formulation and higher dose EBRT seemed to be useful. Although further studies are needed, it seemed to be comparatively difficult to control bone metastases of elderly patients, rib/sternal/facial bone, hepatobiliary/pancreatic/colorectal carcinoma.

It's a matter of time and dosage - intra arterial chemotherapy forcarcinoma of the oropharynx

Advanced head and neck cancer (HNC) patients have good response rates with radiochemotherapy. However, quality of life is often severely affected and the main reason for high rates of suicide. For a deliberately milder treatment, there is an option to selectively treat the tumor region with chemotherapy. This study reports on the treatment of oropharyngeal carcinoma with intra arterial short-term infusion. 55 patients, suffering from inoperable carcinoma of the oropharynx have been treated with intra-arterial short-term infusion chemotherapy via angiocatheters or implanted arterial port catheters. Infusion time of 7 to 12minutes. Patients with high tumor load or lung metastases had additional treatment of isolated thoracic perfusion. Divergent overall survival rates have been noted depending on the pretreatment of the patients. One-, two-, and three-year survival rates of 76 %, 54 % and 35 % for patients without prior irradiation and 40 %, 7 % und 7 % for priorly irradiated patients have been observed. Particularly long overall survival rates have been observed for the subgroup of patients with pretreatment but without irradiation suffering from relapsed cancer, who reached median survival rates of 33.5 months. In contrast, the median survival of irradiated patients suffering from recurrent cancer was 8.2months. Tracheostomy and tube feeding could be avoided in any case. Randomized clinical trials are necessary to support these results. However, small dosages can generate high concentrations in limited volumes and therefore have an increased effect while keeping side effects low.

Impact of Histological and Molecular Parameters on Prognosis of Oral Squamous Cell Carcinoma: Analysis of 290 Cases.

Background Nodal metastasis is a critical factor in predicting the prognosis of oral squamous cell carcinoma (OSCC). When patients present with a clinically positive neck, the treatment of choice is radical neck dissection. However, management of a clinically negative neck is still a subject of significant controversy. Aim This study was carried out in order to propose a model to predict regional lymph node metastasis of OSCC using histological parameters such as tumour stage, tumour size, pattern of invasion (POI), differentiation of tumour, and host immune response, together with the expression levels of six biomarkers (periostin, HIF-1α, MMP-9, β-catenin, VEGF-C, and EGFR), and, furthermore, to compare the impact of all these parameters on recurrence and 3 yr and 5 yr survival rates. Materials and Method. Histological materials collected from the archives were used to evaluate histological parameters and immunohistochemical profiles. Standard methods were used for immunohistochemistry and for evaluation of results. Data related to recurrence and survival (3 and 5 years) was also recorded. Clinical data was collected from patients' records. Results Male to female ratio was 3 : 1. The commonest site of OSCC was the buccal mucosa, and majority of them were T3 or T4 tumours presented at stage 4. 62.5% of the tumours were well differentiated. Three-year and 5-year survival rates were significantly associated with lymph node metastasis and recurrence. POI was significantly correlated with tumour size, stage, 3-year survival, EGFR, HIF-1α, periostin, and MMP-9 (p < 0.05). Expression of EGFR showed a direct association with metastasis (p < 0.05). Conclusion POI, level of differentiation, and expression of EGFR are independent prognostic markers for lymph node metastasis. Therefore, these parameters may help in treatment planning of a clinically negative neck.