Complete Response Group Research Articles

Drug-eluting bead transarterial chemoembolization for hepatocellular carcinoma: does size really matter?

We aimed to compare the safety and effectiveness of 100-300 μm versus 300-500 μm drug-eluting bead transarterial chemoembolization (DEB-TACE) and to investigate the impact of tumor and feeding artery size on treatment outcome of different particle sizes in the treatment of hepatocellular carcinoma (HCC). This retrospective cohort study enrolled 234 consecutive patients who underwent TACE using 100-300 μm DEB (Group A, n=75) and 300-500 μm DEB (Group B, n=159) in a tertiary center between August 2012 and March 2017. Initial treatment response and adverse events were assessed using modified Response Evaluation Criteria in Solid Tumors (mRECIST) and National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, respectively. A total of 704 HCCs in 234 patients were evaluated. The average index tumor size was 3.8 cm. Multivariate analysis showed that tumor size, lobe involvement, particle size, and tumor location were significant predictive factors of complete response. The overall rate of complete response in groups A and B were 56.0% and 33.3% (P = 0.001), respectively. Group A had higher complete response rate than group B in the subgroup of BCLC B with tumor <3 cm (57.9% vs. 21.1%; P = 0.020) and subgroup of feeding artery ≥0.9 mm (55.2% vs. 30.9%; P = 0.014). There were fewer major complications in group A compared with group B (0% vs. 6.9%, P = 0.018). TACE with 100-300 μm DEB is associated with better initial treatment response and fewer major complications compared with 300-500 μm. Our study also highlights the impact of tumor characteristics on treatment outcome of different DEB size, which might help to select the optimal sphere size for TACE in the treatment of HCC.

Prognostic role of baseline 18F-FDG PET/CT metabolic parameters in elderly HL: a two-center experience in 123 patients.

Elderly Hodgkin lymphoma (HL) is an aggressive lymphoma subgroup with high 18F-FDG avidity at 18F-FDG-PET/CT but no shared criteria for PET/CT in treatment evaluation and prediction of outcome are available. The aim of our bicentric study was to investigate whether the metabolic baseline PET/CT parameters can predict treatment response and prognosis in elderly HL. We retrospectively included 123 patients who underwent baseline 18F-FDG-PET/CT and end of treatment PET/CT scans. The PET images were analyzed visually and semi-quantitatively by measuring the lesion to liver SUVmax ratio (L-L SUV R), lesion to blood-pool SUVmax ratio (L-BP SUV R), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Survival curves were plotted according to the Kaplan-Meier method. At a median follow-up of 40months, the median PFS and OS were 29 and 37months. L-BP SUV R, L-L SUV R, MTV, and TLG were significantly higher in patients with no complete response compared with complete response group at end of treatment. Moreover, these parameters were demonstrated to be independent prognostic factors for PFS together with tumor stage, while only L-L SUV R and L-BP SUV R for OS. End of treatment PET/CT results using Deauville criteria were significantly correlated with outcome survival. End of treatment PET/CT results (using Deauville criteria) and semiquantitative baseline PET/CT parameters were significantly correlated with response to treatment and long-term outcome.

Appropriate Candidates for Salvage Esophagectomy of Initially Unresectable Locally Advanced T4 Esophageal Squamous Cell Carcinoma.

Standard treatment for unresectable locally advanced esophageal cancer is definitive chemoradiotherapy (dCRT). Although salvage esophagectomy is the only curative treatment available following dCRT failure, the appropriate candidates for salvage esophagectomy remain unclear. Three hundred seventeen patients who underwent dCRT from April 2004 to December 2016 were stratified into three study groups-a complete response (CR) group, chemotherapy or best supportive care (BSC) group, and salvage esophagectomy group-and compared. We also investigated the clinical outcomes and prognostic factors of salvage esophagectomy. Seventy-one patients (22.4%) achieved CR after dCRT, 18 patients (5.7%) underwent salvage esophagectomy, and 228 patients (71.9%) underwent palliative chemotherapy or BSC. The 5-year overall survival (OS) rates of the CR group, salvage esophagectomy group, and chemotherapy or BSC group were 83.0%, 51.6%, and 1.3%, respectively. Salvage esophagectomy recipients had a worse OS rate than CR patients (p < 0.001) but a better OS rate than those in the chemotherapy or BSC group (p < 0.001). Incomplete resection was the only significant variable associated with poor OS on univariate Cox proportional-hazards analysis (hazard ratio: 7.633, 95% confidence interval: 1.692-34.482; p = 0.008). Patients with tumors in the upper thoracic esophagus were more likely to undergo incomplete resection (p = 0.011). Patients who achieve R0 resection are good candidates for salvage esophagectomy regardless of their response to dCRT. Those with upper thoracic esophageal tumors are at risk of incomplete resection; careful attention is required when considering these patients for salvage esophagectomy.

T Follicular Helper Cells Improve Chronic Hepatitis B Patient Response to Interferon by Promoting B Cell Differentiation and HBsAb Production

Background: Hepatitis B surface antigen (HBsAg) seroconversion is considered the best outcome in the treatment of chronic hepatitis B virus (HBV) infection. In this study, we aimed to determine the cellular and molecular mechanisms by which pegylated interferon alpha (PEG-IFN-α) improves the seroconversion rate of patients with chronic hepatitis B (CHB). Methods: We first examined the significance of circulating T follicular helper (TFH) cells in the therapeutic response to PEG-IFN-α in patients with CHB. Flow cytometry was used to analyze the circulating TFH cells from 15 healthy individuals and 42 patients with CHB who exhibited different treatment responses [complete response group (CRG), incomplete response group (ICRG), and nonresponse group (NRG)] to the standard 48-week regimen of PEG-IFN-α monotherapy. In addition, the capacity of different TFH subsets to activate B cells and stimulate IgG production was examined using co-culture experiments. Findings: Longitudinal analysis revealed specific and significant increases in CD40L+CD4+ CXCR5+ TFH cells in CRG patients compared with NRG and ICRG patients given PEG-IFN-α monotherapy. In vitro co-culture experiments demonstrated that blocking CD40-CD40L signaling, but not ICOS-ICOSL signaling, specifically inhibited B cell activation and IgG production. In addition, HBV may impair the TFH function by boosting inhibitory regulatory T cells. Transcriptome analysis further revealed the upregulation of CD40L, but not ICOS, in TFH cells isolated from CRG patients. Interpretation: TFH cells, particularly those associated with CD40L expression, stimulate B cell differentiation and improve HBsAg seroconversion in patients with CHB following PEG-IFN-α treatment. Funding Statement: This research was funded by the National Natural Science Foundation of China (nos. 30972610, 81273240, 91742107, 81570002), National Key Research and Development Program (nos. 2017YFC0910000, 2017YFD0501300), Jilin Province Science and Technology Agency (nos. 20190101022JH, 2019J026, 20170622009JC, 2017C021, 2017J039, SXGJXX2017-8, JJKH20180197KJ, DBXM154-2018, 2018SCZWSZX-015), and the Fund of the State Key Laboratory of Kidney Diseases in PLA General Hospital (nos.KF-01-147). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The design of this study followed the guidelines of the Declaration of Helsinki and was approved by the Human Ethics Committee of the First Hospital of Jilin University (Changchun, Jilin, China). Written informed consent was obtained from all participants.

Complete pathologic response rate to neoadjuvant chemotherapy increases with increasing HER2/CEP17 ratio in HER2 overexpressing breast cancer: analysis of the National Cancer Database (NCDB).

HER2-positive breast cancer is an aggressive subtype of breast cancer that overexpresses human epidermal growth factor receptor 2 promoting cancer cell growth. Monoclonal antibodies targeting the HER2 receptor have improved survival for this patient population. Achieving pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) has correlated with disease-free survival in multiple trials, but we do not know why some HER2-positive tumors respond better to these therapies. We evaluated the correlation between HER2/CEP17 ratio and partial versus complete response following NAC. We evaluated whether patients with higher HER2/CEP17 ratios would have higher rates of pCR after NAC. Using the National Cancer Database (NCDB), we performed a retrospective review comparing pCR rates after NAC based on HER2 ratio between 2005 and 2014. Patients were excluded if they were HER2 negative, did not undergo NAC, or if the HER2 ratio was not recorded. Trends in percentage of pCR versus partial response were analyzed using SPSS. The NCDB included 237,118 patients with HER2 equivocal or HER2-positive breast tumors. 29,291 of these patients underwent NAC, and HER2/CEP17 ratios were recorded in 14,597 of the NAC cases. A pCR was noted in 9752 patients and 11,402 patients had a partial response. The ratios were significantly different between complete vs. partial response groups (include ratios), P < 0.001. Using linear regression analysis, we identified a direct relationship between increasing the ratio and response to NAC. Our study demonstrates a linear relationship between HER2/CEP17 ratio and pCR to NAC in patients included in the NCDB. The NCDB reflects current clinical practices across the country, and in this patient population, higher HER2 ratio is predictive of pCR to NAC and thus may be used in guiding decisions regarding the therapies that a patient receives in order to enhance pCR.

Identifying Long Non-coding RNA of Prostate Cancer Associated With Radioresponse by Comprehensive Bioinformatics Analysis.

Although radiotherapy is greatly successful in the treatment of prostate cancer (PCa), radioresistance is still a major challenge in the treatment. To our knowledge, this study is the first to screen long non-coding RNAs (lncRNAs) associated with radioresponse in PCa by The Cancer Genome Atlas (TCGA). Bioinformatics methods were used to identify the differentially expressed lncRNAs and protein-coding genes (PCGs) between complete response (CR) and non-complete response (non-CR) groups in radiotherapy. Statistical methods were applied to identify the correlation between lncRNAs and radioresponse as well as lncRNAs and PCGs. The correlation between PCGs and radioresponse was analyzed using weighted gene co-expression network analysis (WGCNA). The three online databases were used to predict the potential target miRNAs of lncRNAs and the miRNAs that might regulate PCGs. RT-qPCR was utilized to detect the expression of lncRNAs and PCGs in our PCa patients. A total of 65 differentially expressed lncRNAs and 468 differentially expressed PCGs were found between the two groups of PCa. After the chi-square test, LINC01600 was selected to be highly correlated with radioresponse from the 65 differentially expressed lncRNAs. Pearson correlation analysis found 558 PCGs co-expressed with LINC01600. WGCNA identified the darkred module associated with radioresponse in PCa. After taking the intersection of the darkred module of WGCNA, differentially expressed PCGs between the two groups of PCa, and the PCGs co-expressed with LINC01600, three PCGs, that is, JUND, ZFP36, and ATF3 were identified as the potential target PCGs of LINC01600. More importantly, we detected the expression of LINC01600 and three PCGs using our PCa patients, and finally verified that LINC01600 and JUND were differentially expressed between CR and non-CR groups, excluding ZFP36 and ATF3. Meantime, the potential regulation ability of LINC01600 for JUND in PCa cell lines was initially explored. In addition, we constructed the competing endogenous RNA (ceRNA) network of LINC01600—miRNA—JUND. In conclusion, we initially reveal the association of LINC01600 with radioresponse in PCa and identify its potential target PCGs for further basic and clinical research.

MP37-14 PROGNOSTIC ROLE OF [ 11 C]CHOLINE PET/CT SCAN IN PATIENTS WITH METASTATIC CASTRATE RESISTANT PROSTATE CANCER UNDERGOING PRIMARY DOCETAXEL CHEMOTHERAPY

You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) III (MP37)1 Apr 2020MP37-14 PROGNOSTIC ROLE OF [11C]CHOLINE PET/CT SCAN IN PATIENTS WITH METASTATIC CASTRATE RESISTANT PROSTATE CANCER UNDERGOING PRIMARY DOCETAXEL CHEMOTHERAPY Masaya Jimbo*, Mohamed Ahmed, Jack Andrews, Manaf Alom, Ayca Dundar, R. Jeffrey Karnes, Alan Bryce, Ayse Kendi, Eugene Kwon, and Michael Bold Masaya Jimbo*Masaya Jimbo* More articles by this author , Mohamed AhmedMohamed Ahmed More articles by this author , Jack AndrewsJack Andrews More articles by this author , Manaf AlomManaf Alom More articles by this author , Ayca DundarAyca Dundar More articles by this author , R. Jeffrey KarnesR. Jeffrey Karnes More articles by this author , Alan BryceAlan Bryce More articles by this author , Ayse KendiAyse Kendi More articles by this author , Eugene KwonEugene Kwon More articles by this author , and Michael BoldMichael Bold More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000886.014AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: We sought to assess the prognostic utility of [11C]choline positron emission tomography/computed tomography (PET/CT) in patients with metastatic castrate resistant prostate cancer (mCRPC) undergoing primary docetaxel chemotherapy. METHODS: We performed a single institution retrospective analysis of 77 mCRPC patients who were treated with 6 cycles of docetaxel chemotherapy, and underwent [11C]choline PET/CT scans at baseline (prior to chemotherapy), mid-course (after 3 cycles), and post-therapy (after 6 cycles). We evaluated treatment response based on change in blood pool-corrected maximum standardized uptake value (SUVmax) of the index lesion on PET/CT, as well as change in serum prostate specific antigen (PSA). Logistic regression analysis was used to identify factors associated with complete treatment response. Progression free survival (PFS) analysis was performed using log-rank test and shown on Kaplan-Meier plot. RESULTS: Change in corrected SUVmax on mid-course scan was a significant predictor of complete response after full 6 cycles of docetaxel chemotherapy on univariable and multivariables analyses (Table). Patients with ≥20% reduction in corrected SUVmax on mid-course scan were 3.6 times more likely to achieve complete response, compared to patients with <20% reduction in corrected SUVmax (p = 0.0420). Change in PSA at mid-course was not a significant predictor of complete response. Median PFS in the complete response group was 34.0 months, compared to 9.5 months in the incomplete response group (p = 0.0014) (Figure). CONCLUSIONS: Our study showed that mid-course and post-therapy [11C]choline PET/CT evaluation for mCRPC patients undergoing primary docetaxel chemotherapy was able to predict full course treatment response and PFS, respectively. [11C]choline PET/CT should be considered as a valuable tool in the repertoire of the treating physician. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e565-e566 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Masaya Jimbo* More articles by this author Mohamed Ahmed More articles by this author Jack Andrews More articles by this author Manaf Alom More articles by this author Ayca Dundar More articles by this author R. Jeffrey Karnes More articles by this author Alan Bryce More articles by this author Ayse Kendi More articles by this author Eugene Kwon More articles by this author Michael Bold More articles by this author Expand All Advertisement PDF downloadLoading ...

Clinical factors of pathological complete response after neoadjuvant chemoradiotherapy in rectal cancer

Objective: To explore the feasibility of clinical factors to predict the pathological complete response after neoadjuvant chemoradiotherapy in rectal cancer. Methods: A retrospective analysis was performed on clinical factors of 162 patients with rectal cancer, who underwent neoadjuvant chemoradiotherapy in the General Hospital of People's Liberation Army from January 2011 to December 2018.According to the postoperative pathological results, the patients were divided into pathological complete response (pCR) group and non-pathological complete response group (non-pCR group) to check the predictive clinical factors for pCR. Results: Twenty-eight cases achieved pCR after neoadjuvant chemoradiation (17.3%, 28/162). Univariate analysis showed that patients with higher differentiation (P=0.024), tumor occupation of the bowel lumen≤1/2 (P=0.006), earlier clinical T stage (P=0.013), earlier clinical N stage (P=0.009), the time interval between neoadjuvant chemoradiotherapy and surgery>49 days (P=0.006), and maximum tumor diameter≤5 cm (P=0.019) were more likely to obtain pCR, and the differences werestatistically significant. Multivariate analysis showed that tumor occupation of the bowel lumen≤1/2 (P=0.01), maximum tumor diameter≤5 cm (P=0.035), and the interval>49 days (P=0.009) were independent factors in predicting pCR after neoadjuvant therapy. Conclusion: Tumor occupation of the bowel lumen, maximum tumor diameter, and the time interval between neoadjuvant chemoradiotherapy and surgery can predict the pCR in rectal cancer.

The Factors Affecting the Efficacy of ?-interferon in the Treatment of (CHB)

Objective: To analyze the factors affecting the efficacy of ?-interferon in the treatment of chronic hepatitis B (CHB). Methods: A total of 100 patients with CHB treated in our hospital from June 2018 to June 2019 were selected. All patients were treated with ?-interferon to evaluate the efficacy, and the factors affecting the effect of ?-interferon on CHB were analyzed. Results: After treatment, 54 patients fully responded and 46 patients did not; the levels of white blood cells, HBV DNA, and HBsAg in the complete response group were lower than those in the incompletely response group, and the differences were statistically significant (P &lt;0.05); Multivariate logistic regression analysis found that serum HBV DNA and HBsAg were independent factors affecting the efficacy of ?-interferon in the treatment of CHB (OR&gt; 1, P&lt;0.05). Conclusion: Serum HBV DNA and HBsAg are risk factors that affect the efficacy of ?-interferon in the treatment of CHB. Monitoring the changes of serum HBV DNA and HBsAg levels has important clinical significance for predicting the efficacy.

Myeloid-Derived Suppressor Cells in Nonmetastatic Urothelial Carcinoma of Bladder Is Associated With Pathologic Complete Response and Overall Survival.

Myeloid-derived suppressor cells (MDSC) have immunosuppressive activity and enhance tumor progression. We hypothesized that lower blood MDSC would correlate with pathologic complete response and better outcomes in nonmetastatic urothelial carcinoma (UC). Before cystectomy, blood MDSC were measured in whole blood (WB) and peripheral blood mononuclear cells using flow cytometry. MDSC were defined as CD33+/HLA-DR-. MDSC subtypes were polymorphonuclear MDSC (CD15+/CD14-), monocytic (M)-MDSC (CD15-/CD14+), and uncommitted (UnC) MDSC (CD15-/CD14-). The Wilcoxon rank sum test was used to compare MDSC between pathologic complete response groups. The optimal cutoff points for MDSC were identified using recursive partitioning analysis with cross-validation. The Cox proportional hazard model was used to associate MDSC and other clinical factors with recurrence-free survival and overall survival (OS). Overall, 109 patients were included: 86% men with median (range) age of 67 (30-88) years, 76% with pure UC, 29% intravesical therapy, and 41% neoadjuvant chemotherapy. Twenty-one patients (19%) had pT0N0 and 23 (24%)< pT2N0. Median (range) follow-up time was 17.4 (0.4-42.4) months. Total MDSC and polymorphonuclear MDSC percentage in peripheral blood mononuclear cells was significantly lower in patients with pT0N0 disease (P= .03). One- and 2-year OS rates were 94% (95% confidence interval [CI], 90-99) and 83% (95% CI, 75-93), respectively. In the multivariate Cox model after adjusting for age and gender, patients with higher WB M-MDSC and UnC-MDSC had shorter OS (optimal cutoff points by recursive partitioning analysis, hazard ratio= 7.5 [95% CI, 2.5-22.8], P=.0004; hazard ratio= 3.4 [95% CI, 1.0-11.0], P= .046, respectively). In patients with nonmetastatic UC of bladder, higher WB M-MDSC and UnC-MDSC before cystectomy had negative prognostic value. Prospective validation is warranted.

Predictive factors for tumour response after the neoadjuvant-treatment of rectal adenocarcinoma

PurposeStandard of care for locally advanced rectal cancer is neoadjuvant chemoradiotherapy followed by surgery. This study identified predictive factors for tumour response in our series. Patients and methodsBetween January 2005 and December 2018, 292 patients with locally advanced rectal cancer treated by preoperative chemo-radiation before surgery were retrospectively analyzed. The radiation dose was 50.4Gy with fluoropyrimidine-based chemotherapy regimens. Patients-tumour and treatment-factors were tested for influence on tumour down staging and regression grade using Mandard scoring system on surgical specimens (TRG). ResultsMedian age was 69 years (range 39–87); 33.9% of patients was Stage II and 54.5% Stage IIIB. Tumour down staging occurred in 211 patients (73%), including 63 patients (21.6%) with ypT0 (documented T0 at surgery) and 148 patients (50.7%) with a satisfactory tumour regression grade defined as TRG2‒3. Upper rectal tumours were identified to predictive factors for pathologic complete response by univariate analysis (p=0.002). TRG1‒3 was associated with intervals from chemo-radiation to surgery (p=0.004); TRG1‒3 rates were higher with longer intervals: 1.71% in ≤ 5 weeks, 23.63% in 6–8 weeks and 46.9% in ≥ 9 weeks; and PTV 50.4≥800cc (p=0.06); 3 and 5years survivals were 85% and 90% for the group as a whole. Among ypT0 cases, the overall survival was 91.1% without significantly different (p=0.25) compared with the remaining group, 87.2%. Among ypT0 cases, the relapse-free survival was 94.5%, with significantly different (p=0.03) compared with the remaining group 78.2%. There were no treatment-associated fatalities. Thirty-two patients (10.96%) experienced Grade III/IV toxicities (proctitis, ephitelitis and neutropenia). ConclusionsTumour localization was identified as predictive factors of pathologic complete response for locally advanced rectal cancer treated with preoperative chemo-radiation. Upper rectal tumours are more likely to develop complete responses. Delay in surgery was identified as a favorable predictive factor for TRG1‒3. The relapse-free survival in pathologic complete response group was higher compared with non-pathologic complete response.

Effects of transarterial chemoembolization on regulatory T cell and its subpopulations in patients with hepatocellular carcinoma.

Regulatory T cell (Treg) plays an essential role in regulating anti-tumor immunity. The aim of this study was to investigate the effect of transarterial chemoembolization (TACE) on Treg in hepatocellular carcinoma (HCC) patients. The frequency of peripheral blood Tregs in 27 HCC patients who underwent TACE were measured at baseline and 1month after TACE. The frequency of peripheral blood Tregs at baseline were compared with those in 23 healthy controls. Tregs were further classified into three subpopulations [Treg (I), Treg (II), Treg (III)] based on expression levels or markers and their function. The patients were divided into two groups according to tumor response after TACE; complete response group and incomplete response group. The correlations between the frequency of Treg and clinical factors were analyzed. The frequency of Treg in HCC patients (7.52%) was significantly higher than in healthy controls (4.99%) at baseline. Regarding Treg subpopulations, the frequency of Treg (II) was significantly higher in HCC patients (2.51%) than in healthy controls (0.60%). In comparison of Treg numbers at baseline and post-TACE by tumor response, the change of Treg (III) in complete response group from baseline to post-TACE was significantly decreased (63.8 → 53.2/mm3). Patients with a high post-TACE Treg (III) (3.8months) exhibited a significantly shorter median time to progression than those with a low post-TACE Treg (III) (11.6months). In multivariate analyses, hypoalbuminemia (hazard ratio 3.324; 95% CI 1.098-10.063, p = 0.034) and high post-TACE Treg (III) (hazard ratio 3.080; 95% CI 1.091-8.696, p = 0.034) were significant factors for associating with progression. The frequency of Tregs in HCC patients was significantly higher than in healthy controls. In addition, patients with a high post-TACE Treg (III) exhibited a significantly lower progression-free survival rate than those with a low post-TACE Treg (III).

The Five-Year Survival Rate of Patients with Nasopharyngeal Carcinoma Based on Tumor Response after Receiving Neoadjuvant Chemotherapy, Followed by Chemoradiation, in Indonesia: A Retrospective Study

Introduction: Nasopharyngeal cancer (NPC) is a common malignancy in Southeast Asia with a high mortality rate. Previous studies have shown that the patient survival rate is <80% worldwide. At the Dharmais Cancer Hospital, NPC is the first of the top 10 diseases with the highest rate of stage III cancer progression. Objective: This study aims to determine the 5-year survival rate of patients with NPC based on tumor response and their prognostic factors after receiving neoadjuvant chemotherapy, followed by chemoradiation. Methods: The records of 261 patients between January 2009 and December 2013 were retrospectively analyzed. All patients with NPC who received neoadjuvant chemotherapy, followed by chemoradiation, at the Dharmais Cancer Hospital from 2009 to 2013 were identified. Patients with metastasis were excluded. The primary endpoint of this study was overall survival, which was defined as the time from the date of treatment to the date of death. The survival curve was analyzed using the Kaplan-Meier method. The Cox proportional hazard model was used for the multivariate analysis of prognostic factors. Results: The tumor response rates for patients with complete response (CR), partial response (PR), and progressive disease (PD) were 33.7, 45.2, and 21.2%, respectively. The 5-year overall survival rate was 38.6%. The 5-year survival rates based on tumor response among CR, PR, and PD patients were 71.0, 30.4, and 10.6%, respectively. The significant independent prognostic factors were tumor response, educational background, job, alcohol consumption, clinical stage, and prompt treatment. Conclusion: The survival probability of patients with NPC receiving neoadjuvant chemotherapy, followed by chemoradiation, was higher in the CR group than in the PR and PD groups. This confirms that early detection can improve the patient’s survival. Long-term follow-up is required to determine the factors influencing tumor response in NPC.

The correlation of response to induction chemotherapy with neutrophil lymphocyte ratio and platelet lymphocyte ratio in oral cavity malignancy

Aims and Objectives: Induction chemotherapy yields significant response in locally advanced squamous cell carcinoma of oral cavity. Pre-treatment biomarkers can help to predict response to chemotherapy. The neutrophil–lymphocyte ratio (NLR), and platelet lymphocyte ratio (PLR) are cost-effective and simple parameters that can predict response to chemotherapy. This study aims to find the correlation between NLR, PLR and response to induction chemotherapy in oral cavity malignancies. Materials and Methods: Details of 32 patients with locally advanced squamous cell carcinoma of oral cavity who received induction chemotherapy from Jan 2017- March 2019 were collected and the following were recorded. Pre-treatment total leukocyte count, neutrophil, lymphocyte and platelet counts. Post induction chemotherapy, reduction in size of tumour. Patients were categorised into complete, partial and non- responders.The mean NLR and PLR, and the significance in variation of NLR and PLR between the three groups was calculated and the statistical significance analysed. Results: The mean NLR is significantly low in both partial (2.62) and complete response groups (2.4) compared to the patients with static response (5.6). The mean PLR is also low in responders (124) when compared to the static group (180), but it is not statistically significant. With a cut-off value of 3.95 for NLR and 153 for PLR, response could be predicted with high positive predictive value. When both the ratios are combined the predictive value is further increased as shown in this study. Conclusion: Pre-treatment NLR and PLR are reliable biomarkers of the systemic immunologic phenotype of the cancer patients. They predict the response to chemotherapy in patients with oral cavity malignancy. Keywords: Neutrophil lymphocyte ratio, Platelet lymphocyte ratio, Oral cavity cancer, Induction chemotherapy.

Evaluation of health-related quality of life and affecting factors in child with enuresis

Enuresis is a common problem in children and distressing condition that can have an impact on the child's behavior and on their emotional and social life. Health-related quality of life (HRQoL) is defined as an individual's perception of the impact of the disease and treatment. The aim of this study was to evaluate the HRQoL in Turkish children with enuresis and to investigate the effect of independent sociodemographic and clinical variables on HRQoL in children with enuresis. 110 children with enuresis and their mothers and 120 healthy children and their mothers were included in the study. The German quality of life questionnaire (KINDL®) scales were used to assess the children's HRQoL. For comparing the data of children with enuresis and healthy children, a two-sided unpaired t-test and linear regression model were used. The total HRQoL score for the children with enuresis group was 63.14±21.98 and for the children in the control group was 75.6±10.1 (P<0.001). After adjusting for sex and age using the unstandardized coefficient of regression model, HRQoL score for the children with enuresis still remained statistically significant lower than that for healthy peers (64.21± vs 75.11± P<0.001). The HRQoL subscale scores showed that children with enuresis had lower emotional well-being scores (64.23±14.2 vs 78.9±11.4, P<0.001), self-esteem score (62.23±11 vs 68.6±17.4, P=0.001), family relationship score (76.23±2 vs 83.4±12.2, P=0.042), and friendship score (62.4±13.2 vs 68.8±15.3, P=0.023) compared to the control group. When the effects of independent sociodemographic factors and clinical variables on HRQoL were evaluated, it was seen that the presence of lower urinary tract symptoms (LUTS) negatively affected total HRQoL score (59.89±11.2 vs 69.29±10.9 P=0.028). Also the total HRQoL score was higher in treated children with enuresis than in nontreated children (65.96±12.1 vs 55.27±10.1 P=0.032). Among the treated children, complete treatment response group had higher total HRQoL score compared to partial treatment response group and nonresponse group (respectively, 70.98±9.7, 65.25±10.1, 60.45±10.9, P=0.034, P=0.01) (Summary Figure). Family income level affected total HRQoL score, low-income group had lower total HRQoL score compared to high-income group (62.17±11.9 vs 69.25±10 P=0.039). This study demonstrated that enuresis negatively affects the HRQoL of children and most affected domains in HRQoL were self-esteem, emotional well-being, and their relationship for family and friends. Our presented study showed that HRQoL was lower in non-primary monosymptomatic nocturnal enuresis (non-PMNE) children, nontreated patients. Also there were higher HRQoL scores in patients who had a total or partial response to treatment. Our study may indicate that, low-income children with enuresis, nontreated enuretic children, and presence of LUTS should be considered as a risk group for low HRQoL.

Do microsatellite instability (MSI) and deficient mismatch repair (dMMR) affect the pathologic complete response (pCR) in patients with rectal cancer who received neoadjuvant treatment?

Recently, individualized approaches for the treatment of locally advanced rectal cancers (RC) have been introduced to determine the most beneficial one for boosting the tumor response and assessing the response more accurately. However, despite each patient and tumor have different molecular features, the studies at the molecular level are very limited. In this study, examining the clinical factors which are predictive of pathologic complete response (pCR), helping to determine a treatment program for the management of patients with locally advanced RC, and evaluating the relation between regression grade and MMR-MSI were aimed. 341 RC cases who had undergone surgery were included and divided into three groups according to their response to neoadjuvant treatment. The following parameters were analyzed for all patients: age at diagnosis, sex, tumor location, tumor differentiation, TNM stage, histological subtype, CEA (mean: < 5ng/ml) level, lymphovascular-neural invasion, presence of mucinous subtype, grade, MMR, and MSI statuses. 147 patients (43.2%) had no response (group 1), 141 patients (41.3%) had an intermediate response (group 2), and 53 patients (15.5%) had a complete response (group 3). Neoadjuvant chemoradiotherapy was used in all of the patients with the same protocol. Multivariate analysis revealed that clinical T stage (p: 0.099) and MMR (p: 0.048) were the parameters which were significantly associated with pCR. Since MMR and MSI statuses were found to affect pCR, more careful patient selection for "watch and wait" protocol and further studies on molecular structures of the tumors for individualized therapies are required.

Prediction of Neoadjuvant Radiotherapy and Chemotherapy for Locally Advanced Rectal Cancer Based on 3.0T MRI Intravoxel Incoherent Motion Diffusion Weighted-Imaging with Fe3O4 Nanocontrast Agent

The purpose of this study was to preliminarily explore the feasibility of pre-treatment intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for predicting the efficacy of neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC). Fifty-four patients underwent preoperative IVIM-DWI before (pre-nCRT) and after nCRT (post-nCRT). The values of pre-nCRT and post-nCRT IVIM-DWI parameters (apparent diffusion coefficient standard (ADC), true diffusion coefficient (D), pseudodiffusion coefficient (D*) and perfusion fraction (f), together with the percentage changes (Δ% parametric value) induced by nCRT, were compared between pathological complete response (pCR) and non-pCR groups. After nCRT, the ADC and Dvalues for LARC increased significantly (all P &lt;0.05). The TRG score revealed positive correlations with pre f (r = 0.357, P = 0.020), postD (r =0.551,P &lt;0.001), and Δ%D (r =0.605, P &lt;0.001). The pCR group (n =10) had higher preD *, pref, postD, Δ%ADC, and Δ%D values than the non-pCR group (n =32) (allP &lt;0.05). The GR group (n =15) exhibited higher postD, %ADC, and %D values than the PR group (n =27) (allP &lt;0.05). Based on ROC analysis, Δ%D had a higher area under the curve value than Δ%ADC (P =0.009) in discriminating the pCR and non-pCR groups. IVIM-DWI may be helpful in identifying pCR to nCRT for LARC and is more accurate than traditional DWI.

The Quest for Indicators of Profound Hematologic Response in AL Amyloidosis: Complete Response Remains the Optimal Goal of Therapy

Background: The International Society of Amyloidosis validated the criteria of hematologic response to therapy in AL amyloidosis, based on the reduction of free light chain (FLC) concentration and serum and urine immunofixation. Complete response (CR) predicted the longest survival and was defined by negative serum and urine immunofixation (s&amp;u-IFE) with a normal FLC ratio (FLCR). Subsequently, we and others showed that, in patients with a difference between involved and uninvolved FLC (dFLC) between 20 and 49 mg/L, achieving a dFLC &lt;10 mg/L was associated with an improvement of overall and renal survival. This criterion was then proposed as a goal of therapy in the general population of patients with AL amyloidosis. These studies questioned whether the definition of CR should be reconsidered. In the present study, we compared the outcome of patients who obtained a profound reduction of FLC but do not qualify for CR with the outcome of subjects who reached CR. Methods: The prospectively maintained database of the Pavia Amyloidosis Center was searched for patients who were newly-diagnosed between 2004 and 2018 and who reached at least one the following endpoints 6 months after treatment initiation: 1) complete response (CR) or, in patients who do not qualify for CR, 2) normalization of involved-FLC concentration (normal-iFLC group), dFLC &lt;10 mg/L (dFLC10 group) and normalization of FLCR (normal-FLCR group). We calculated overall survival (OS) and time to next line of therapy or death (TNTD) from the time of response assessment (6 months after treatment initiation). Results: A total of 434 patients (Table) were included, that were divided into the following groups: CR (161), normal-iFLCN (114), dFLC10 (144) and normal-FLCR (220). As expected, there was a partial overlap between the non-CR groups. No difference was seen between the CR and all the other groups in baseline variables: age, sex, organ involvement, Mayo 2004/European staging, and renal staging. Treatment was bortezomib-based in 261 subjects, melphalan/dexamethasone (MDex) in 128, IMiDs-based in 21, autologous stem cell transplant in 14, and therapy for IgM clones in the remaining 10 subjects. The reasons for not qualifying for CR in the normal-iFLC group was abnormal FLCR only in 4 (3%), positive s&amp;u-IFE only in 81 (72%), and both in 29 (25%). The reason for not qualifying for CR in the dFLC10 group was abnormal FLCR only in 4 (3%), positive s&amp;u-IFE only in 104 (72%) and both in 36 (25%). The median follow-up of living patients was 60 months. Patients who achieved CR enjoyed a significantly longer OS (58% alive at 10 years) compared to patients who reached any of the other endpoints but did not qualify for CR (Figure). Also median TNTD was significantly longer in patients who obtained CR (75 months) compared to the normal-iFLC group (33 months, P&lt;0.001), the dFLC10 group (39 months, P&lt;0.001), and the normal-FLCR group (24 months, P&lt;0.001). We then evaluated whether achieving a normal iFLC or a dFLC &lt;10 mg/L was associated with a better survival among patients who did qualify for CR. In the CR group, 103 (64%) patients achieved a normal iFLC and 86 (53%) a dFLC &lt;10 mg/L. There was no significant difference in OS and TNTD between subgroups of patients in CR according to iFLC or dFLC response. Conclusion: Undetectable clonal disease by both negative serum and urine IFE and normal FLCR (CR) is associated with best survival in AL amyloidosis and should be the goal of therapy if tolerability and patient frailty allow. However, it is possible that novel immunotherapies, such as daratumumab, affect the concentration of uninvolved FLC, thus interfering with dFLC and FLCR, and this study should be validated in patients exposed to these agents. Approximately 40% of patients in CR relapse and eventually die. New sensitive tools to identify residual clonal disease (mass-spectrometry on serum and urine, next generation sequencing and next generation flow cytometry on bone marrow) are urgently needed to detect these patients and intervene before relapse. Disclosures Milani: Janssen: Honoraria; Pfizef: Honoraria. Palladini:Janssen-Cilag: Other: Travel grant; Janssen-Cilag: Honoraria; Celgene: Other: Travel grant; Sebia: Honoraria.

Survival Outcomes After Adding Stereotactic Body Radiotherapy to Metastatic Renal Cell Carcinoma Patients Treated With Tyrosine Kinase Inhibitors.

Long-lasting control is rarely achieved with tyrosine kinase inhibitors (TKI) alone in metastatic renal cell carcinoma (mRCC). Our study aimed to investigate the survival outcomes of adding stereotactic body radiotherapy (SBRT) to TKI in mRCC. From September 2015 to September 2018, 56 patients treated with TKI received SBRT for 103 unresectable lesions. A total of 24 and 32 patients were irradiated before and after TKI failure, respectively. Overall survival (OS) was calculated from metastases. Progression-free survival (PFS) was calculated from SBRT. Overall, 10, 32, and 12 patients had International Metastatic Renal Cell Carcinoma Database Consortium favorable, intermediate, and poor risk. Median follow-up was 21.7 months (range, 5.1 to 110.6 mo). Median OS was 61.2 months. The median PFS was 11.5 months, while the 2-year LC rate was 94%. Sixteen (34%) lesions achieved complete response (CR) in patients irradiated before TKI failure, whereas only 4 (7%) lesions yielded CR in those irradiated after TKI failure (P=0.001). The median PFS in CR group was significantly longer than that of non-CR group (18.9 vs. 7.1 mo; P=0.003). The 5-year OS in CR group was 86%, compared with 48% in non-CR group (P=0.010). Four (7%) patients experienced Grade 3 toxicity. Adding SBRT to TKI is safe and seems to improve survival in mRCC. Patients irradiated before TKI failure have higher CR rate, and the favorable local response might turn into survival benefit.

A Qualitative Transcriptional Signature for Predicting Recurrence Risk for High-Grade Serous Ovarian Cancer Patients Treated With Platinum-Taxane Adjuvant Chemotherapy.

Resistance to platinum and taxane adjuvant chemotherapy (ACT) is the main cause of the recurrence and poor prognosis of high-grade serous ovarian cancer (HGS-OvCa) patients receiving platinum-taxane ACT after surgery. However, currently reported quantitative transcriptional signatures, which are commonly based on risk scores summarized from gene expression, are unsuitable for clinical application because of their high sensitivity to experimental batch effects and quality uncertainties of clinical samples. Using 226 samples of HGS-OvCa patients receiving platinum-taxane ACT in TCGA, we developed a qualitative transcriptional signature, consisting of four gene pairs whose within-samples relative expression orderings could robustly predict patient recurrence-free survival (RFS). In two independent test datasets, the predicted non-responders had significantly shorter RFS than the predicted responders (log-rank p < 0.05). In a test dataset containing data for patient pathological response state, the signature reclassified 12 out of 22 pathological complete response patients as non-responders and two out of 16 pathological non-complete response patients as responders. Notably, the 12 predicted non-responders in the pathological complete response group had significantly shorter RFS than the predicted responders (log-rank p = 0.0122). This qualitative transcriptional signature, which is insensitive to experimental batch effects and quality uncertainties of clinical samples, can individually identify HGS-OvCa patients who are more likely to benefit from platinum-taxane adjuvant chemotherapy.