Predictive Factors For Treatment Response Research Articles

Efficacy and Safety of Luspatercept in Adult Patients with Transfusion-Dependent Anemia Due to Very Low, Low and Intermediate Risk Myelodysplastic Syndromes (MDS) with Ring Sideroblasts, Who Had an Unsatisfactory Response to or Are Ineligible for Erythropoietin-Based Therapy: A Retrospective Multicenter Study By Fondazione Italiana Sindromi Mielodisplastiche (FiSiM ETS)

Background: Patients with lower-risk myelodysplastic syndromes (MDS) who develop red blood cells (RBC) transfusion-dependent anemia, experience worse quality of life and shorter survival. Therapeutic strategies after failure of erythropoiesis stimulating agents (ESAs) are limited. Regulatory approval of luspatercept in lower-risk MDS with ring sideroblasts (MDS-RS) offers a novel approach for the treatment of transfusion-dependent anemia in this subset of patients. However, data about luspatercept effectiveness in a real-world clinical setting are lacking. Here we report the results of a multicenter retrospective study including patients who were treated with luspatercept within the Italian compassionate use program. Methods: Eligible patients were ≥ 18 years old, had MDS-RS (2016 WHO classification), met criteria for very low, low, or intermediate IPSS-R risk; were receiving regular RBC transfusions (≥2 units/8 weeks in the 16 weeks before study entry); were refractory to or unlikely to respond to ESAs. Primary end point was transfusion independence (TI) for 8 weeks or longer during weeks 1 through 24; key secondary end point was TI for 12 weeks or longer, assessed during both weeks 1 through 24 and weeks 1 through 48. Other secondary end points included erythroid response (defined by the IWG 2006 criteria), progression to acute myeloid leukemia (AML) and safety analyses. Exploratory analyses were performed to identify predictive factors for treatment response. Results: 184 patients who were enrolled in the Italian luspatercept compassionate use program between December 2020 and December 2021 were analyzed in this study. Median age at enrollment was 74 years (range, 31-88), median time since diagnosis was 43 months, and median time since onset of transfusion-dependence was 23 months. Overall, 123 (66.8%) patients had at least one comorbidity requiring ongoing treatment, 39 (21.2%) had at least three. Baseline median transfusion burden was 6 RBC units every 8 weeks (range, 2-25). At the time of data analysis (June 30, 2022), 130 (73.4%) patients completed at least 24 weeks of treatment. Median time on treatment was 301.5 days, and median follow-up time was 376 days. During the first 24 weeks of the trial, 59 (32%) patients had TI for 8 weeks or longer. The percentage of patients achieving TI increased to 38.6% in the first 48 weeks of the trial. Median duration of TI was 27.9 weeks. Focusing on secondary endpoints, 36 patients (19.6%) had TI for 12 weeks or longer during the first 24 weeks, 52 (28.3%) had TI for 12 weeks or longer considering the first 48 weeks of the trial. A reduction ≥ 4 RBC units/8 weeks during weeks 1-24 was seen in 66 patients (40.2%). Four (2.2%) patients evolved to AML. Serious adverse events were recorded in 27 (15.2%) patients and led to study discontinuation in 5 (2.8%). Overall, treatment was discontinued in 72 (40.7%) patients, mainly for lack of benefit (table 1) The maximum approved dose (1.75 mg/kg) of luspatercept was administered at least once in 144 (81%) patients. Among patients who achieved TI for 8 weeks or longer in the first 48 weeks, luspatercept dose (mg/kg) at response was 1, 1.33 and 1.75 in 31 (46.3%), 18 (29.9%) and 18 (29.9%%) patients, respectively. Logistic regression analysis showed that higher baseline transfusion burden was significantly associated with a lower probability of achieving TI. We identified 3 group of patients stratified according to baseline transfusion burden (group 1, ≤4 units/8 weeks; group 2, 5 to 7 units/8 weeks, group 3, ≥8 units/8 weeks) with a significantly different probability to achieve both the primary endpoint (51.9%, 35.2% and 16.7%, respectively, P<0.01) and the key secondary endpoint (30.8%, 24.1% and 9%, respectively, P<0.01). Patients with higher transfusion burden had higher luspatercept doses at first response (table 2). In patients with low probability to achieve TI (group 2 and 3), a reduction in transfusions equal or greater than 4 units/8 weeks was achieved in 66 (46.2%). Conclusion: Luspatercept was effective for the treatment of transfusion-dependent anemia in MDS-RS in a real-life setting. The benefit extended beyond the achievement of TI and produced a significant reduction in the number of RBC transfusions. Higher baseline transfusion burden was associated with a reduced probability to achieve TI; in these patients, the reduction of transfused RBC units appears a more reliable treatment target. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The role of KRAS and NRAS mutation detection in determining the therapy strategy for colorectal cancer

Colorectal cancer is one of the most frequently diagnosed malignant tumors in men and women, which is a highly heterogeneous group of neoplasms consisting of subclasses with different molecular and clinical characteristics, and, as a consequence, patients with different types of tumors require different treatment protocols. Among the predictive factors of treatment response in patients with metastatic colorectal cancer, the most studied are the genes of the RAS family (KRAS, NRAS). Determination of RAS status is the first step in individual selection of drug therapy in patients with metastatic colorectal cancer. Patients with certain mutations in KRAS and NRAS genes are resistant to anti-EGFR therapy and have a lower median survival than WT (wild type) genotypes, indicating a negative prognosis in the presence of mutations.

Predicting acupuncture efficacy in fibromyalgia: results of a pragmatic open-label study.

To identify the predictive factors of treatment response to acupuncture in patients with fibromyalgia (FM). Patients with FM refractory to standard drug therapy underwent eight weekly acupuncture sessions. Significant improvement, defined as a reduction of at least 30% of the revised Fibromyalgia Impact Questionnaire (FIQR), was assessed at the end of the eight weeks (T1) of treatment and three months after the end of treatment (T2). Univariate analysis was conducted to identify predictors of significant improvement at T1 and T2. Variables that resulted to be significantly associated with clinical improvement at univariate analysis were included in multivariate models. Analyses were conducted on 77 patients (9 males, 11.7%). At T1, significant improvement in FIQR was recorded in 44.2% of patients. At T2, persistent significant improvement was recorded in 20.8% of patients. In the multivariate analysis, predictive variables of treatment failure were tender point count (TPC) (odds ratio [OR] =0.49, 95% confidence interval [95% CI]: 0.28-0.86, p=0.01) and pain magnification (OR=0.68, 95% CI: 0.47-0.99, p=0.04) assessed with the Pain Catastrophising Scale, at T1. At T2, the only predictive variable of treatment failure was concomitant duloxetine use (OR=0.21, 95% CI: 0.05-0.95, p=0.04). High TPC and a tendency for pain magnification predict immediate treatment failure, while duloxetine therapy predicts it three months after completion of the acupuncture course. The identification of clinical characteristics of unfavourable response to acupuncture could help to implement a cost-effective prevention of treatment failure in FM.

Prediction of treatment response following ethanol sclerotherapy of renal cysts by computed tomography.

To investigate predictive factors of treatment response following ethanol sclerotherapy of large renal cysts via computed tomography (CT). Retrospective study reviewed 71 patients (61.0 ± 13.2years; M:F = 32:39) who underwent pretreatment CT and were treated with sclerotherapy of a large (> 5cm) renal cyst (mean volume: 279.8cc) using 99% ethanol from January 2010 to February 2019. Patients were followed up at least two times, short-term (defined as < 6months, median 2.1months) and long-term (defined as > 1year, median 15.5months), via ultrasound or CT. Suboptimal response was defined as the volume of residual cyst > 20mL in each follow-up. Predictive variables of radiologic findings and radiomics features were analyzed using logistic regression analysis. Suboptimal response rates were 33.8% and 18.3% at short-term and long-term follow-ups, respectively. In radiologic findings, patients with suboptimal response in the short-term follow-up showed a more frequent estimated cyst volume ≥ 270mL (OR 14.8, 95% CI 3.9-55.9, p < 0.001) and sinus protrusion (OR 7.0, 95% CI 1.7-28.5, p = 0.007). Cyst volume ≥ 270mL was also associated with suboptimal response in the long-term follow-up (OR 4.6, 95% CI 1.3-16.9, p = 0.021). When radiomics features were combined, the area under the curve increased from 0.83 to 0.86 and from 0.68 to 0.82 to predict suboptimal response in short-term and long-term follow-ups, respectively. Greater estimated volume, sinus protrusion, and radiomics features of the cysts in pretreatment CT can help predict suboptimal response of renal cyst after sclerotherapy.

What is the link between the antidepressants, the transcranial magnetic stimulation and the peripheral vascular endothelial growth factor?

IntroductionVascular endothelial growth factor (VEGF) has been implicated in mediating the effect of antidepressants (AD) and electroconvulsive therapy on depression since it plays a significant role in the neurogenesis. However, the serum VEGF level has not been investigated so far in association with rTMS treatment in patients with major depressive disorder (MDD).ObjectivesThe aim of our study was to compare the effect of the antidepressants and of the repetitive transcranial magnetic stimulation on the serum vascular endothelial growth factor and its association with the responsiveness to the treatments.MethodsA dataset of 50 patients with TRD who were treated with AD (n=33) and bilateral rTMS for 2x5 days (n=17) was analysed (sample ’rTMS&amp;AD’). Montgomery-Asberg Depression Scale (MADRS) was used for monitoring the symptom changes. The serum VEGF levels and symptoms were assessed on the first (V1), on the 14th (V2) and on the 28th day (V3). The VEGF levels were measured by ELISA assay.ResultsThe baseline VEGF levels were significantly higher in non-responders both in the rTMS&amp;AD (p=0.04) and AD samples (p=0.02) compared to responders. The MADRS reduction and the changes in VEGF levels between V1 and V3 were significantly associated in responders only in the AD&amp;rTMS sample (p=0.03). The baseline VEGF level has been proven as a significant predictive factor of treatment response in the total sample (p=0.018).ConclusionsThe baseline VEGF level can be a predictive factor to be a non-responder to different treatments. Change of the VEGF level is associated with the improvement of depressive symptoms only due to rTMS.DisclosureThis study was supported by the FK 131315 grant of the National Research, Development and Innovation Office, Hungary. Authors declare no conflict of interest.

Early patient-reported outcomes are a promising predictive factor of cancer progress and outcome in older patients: The EPROFECY study.

12045 Background: Contrary to commonly-held beliefs, older patients (OPs, aged 70 or more) in oncology are compliant with the use of a telemonitoring digital platform. Such a tool allows the medical team to gain detailed knowledge of the tolerance profile of patients, and help monitor and maintain their quality of life, which is a particularly important goal for older patients. The EPROFECY study assesses the predictive power of the patient health status in the first month of treatment, evaluated with the digital telemonitoring platform Cureety, on survival. Methods: This prospective study was conducted at the Military Hospital Bégin on OPs. Patients were allowed to respond to a symptomatology questionnaire based on CTCAE v.5.0, personalized to their pathology and treatment. An algorithm evaluated the patient status based on reported adverse events: correct (A), compromised (B), to be monitored (C) and critical state (D). For A/B (good health status), the patient received therapeutic advice to help manage each of the reported adverse events. For C/D (poor health status), the patient was invited to call the hospital. To assess the early tolerance of patience to their treatments, we determined the health status in the 1st month after initiation of treatment, which was classified as “Good health” (GH, majority of A/B reports) or “Poor health” (PH, majority of C/D reports). The primary endpoint was to assess if the first-month tolerance is a predictive factor of progression free-survival (PFS). The secondary endpoint was to assess if the first-month tolerance is a predictive factor of overall survival (OS). Results: Sixty-one patients were enrolled between July 1st, 2020 and September 30th, 2021. The median age was 78.0 years (range 70.0 – 99.0), with 81% presenting a metastatic stage, and the most represented cancer being prostate cancer. The median follow-up was 8.2 months. Overall, 2299 ePRO were completed, 89% (n= 2036) corresponding to a "correct" or a "compromised" state and only 11% (n=263) corresponding to a state "to be monitored" or "critical". Based on the first month of questionnaires, 62% of the patients were classified in the GH group, and 38% in the PH group. The PFS ratio at 6 months was 64.6 % in GH vs 23.4 % in PH (HR = 0.1980, 95% CI = 0.04431–0.8845, p = 0.0339). The OS ratio at 6 months was 100% in GH versus 95.5 % in PH (HR: 0.69, 95 % CI = 0.06 – 8.29, p = 0.77). Conclusions: This is the first study that assesses the use of PRO-based tolerance as a predictive factor of treatment response in older individuals. We demonstrated here a significant 80% reduction in the risk of progression in OPs that exhibited a good first-month tolerance. This suggests that e-PRO follow-up might be an effective predictor of response and a tool to treatment plan.

Monitoring early dynamic changes of plasma cell-free DNA and pretreatment pre-albumin to predict chemotherapy effectiveness and survival outcomes in advanced non-small cell lung cancer.

BackgroundThis study aimed to determine whether plasma cell-free DNA (cfDNA) and pretreatment parameters provide useful therapeutic response and prognostic information for advanced non-small cell lung cancer (NSCLC) patients.MethodsA total of 114 patients with advanced NSCLC who underwent systemic chemotherapy were included in this study. Detection of plasma cfDNA concentration and blood parameters before and at the sixth week after treatment was performed. The prognostic value of cfDNA dynamic changes and laboratory parameters was determined via a receiver operating characteristic (ROC) curve, and then analyzed by comparing with the therapeutic efficacy and progression-free survival (PFS). Based on the ROC curve, it revealed a pretreatment pre-albumin (PA) concentration of 21.7 mg/dL was the cut-off value. The Cox proportional hazards regression model was used to evaluate the predictive factors for treatment response and PFS via univariate and multivariate analyses.ResultsPatients with cfDNA reduction ≥20% at the sixth week after treatment reported a significantly better disease control rate (DCR) and prolonged PFS (median PFS: 10.0 vs. 4.0 months, P<0.001). The median PFS of low PA group (PA <21.7 mg/dL) was 6.0 months, while the median PFS of high PA group (PA ≥21.7 mg/dL) was 8.0 months. The combined assessment of cfDNA and pretreatment pre-albumin was associated with significantly better survival outcomes compared with the remaining population (P<0.001). Multivariate analysis for DCR indicated that cfDNA reduction ≥20% was an independent factor (OR =0.419, P=0.001). In addition, multivariate analysis identified 6 significant factors associated with PFS: cfDNA reduction of ≥20%, age <65 years, Eastern Cooperative Oncology Group (ECOG) score ≥2, driver gene mutation, chemotherapy combined regimen, and treatment response of complete response (CR) and partial response (PR). The nomogram could predict the 2-year PFS probability of advanced NSCLC patients after treatment, and the C-index was 0.817.ConclusionsMonitoring cfDNA changes and pretreatment pre-albumin level in advanced NSCLC patients receiving treatment is an accurate predictor of tumor response and PFS. Combined assessment of cfDNA and pretreatment pre-albumin is helpful for predicting survival outcomes. These findings may assist in identifying high-risk patients and guiding treatment strategies.

Liver MRI and clinical findings to predict response after drug eluting bead transarterial chemoembolization in hepatocellular carcinoma

To identify the gadoxetic acid (GA)-enhanced magnetic resonance imaging (MRI) and laboratory findings that enable prediction of treatment response and disease-free survival (DFS) after the first session of drug eluting bead transarterial chemoembolization (DEB-TACE) in patients with hepatocellular carcinoma (HCC). A total of 55 patients who underwent GA-enhanced MRI and DEB-TACE from January 2014 to December 2018 were included. All MRI features were reviewed by two radiologists. Treatment response was evaluated according to the modified Response Evaluation Criteria in Solid Tumors. Univariate and multivariate logistic regression analyses were used to determine predictive factors of treatment response and DFS, respectively. A total of 27 patients (49.1%) achieved complete response (CR) after one session of treatment. There were no significant differences between the two groups in terms of clinical and laboratory characteristics. Heterogeneous signal intensity in the hepatobiliary phase (HBP) was the only independent predictor of non-CR (odds ratio, 4.807; p = 0.048). Recurrent HCC was detected in 19 patients (70.4%) after CR. In the multivariate analysis, elevated serum alpha-fetoprotein (AFP) level (≥ 30 ng/mL) was the only significant parameter associated with DFS (hazard ratio, 2.916; p = 0.040). This preliminary study demonstrated that heterogeneous signal intensity in the HBP and high serum AFP were useful predictive factors for poor treatment response and short DFS after DEB-TACE, respectively.

Navigated micropulse laser for central serous chorioretinopathy: Efficacy, safety, and predictive factors of treatment response.

There is no widely accepted treatment for persistent/chronic central serous chorioretinopathy. The present study aimed to evaluate the efficacy, safety, and factors associated to treatment response to navigated micropulse laser in chorioretinopathy. Retrospective observational case series including consecutive patients presenting with symptomatic persistent and chronic chorioretinopathy. All patients were treated with 5% navigated micropulse laser with the Navilas system (Navilas®, OD-OS GmBH, Teltwo, Germany), by overlying fluorescein angiography, indocyanine green angiography and/or spectral domain-optical coherence tomography images of visible leaking points and/or choroidal hyperpermeability/subretinal fluid to plan the laser treatment. Thirty-nine eyes of 36 consecutive patients (29 men and 7 women, with a mean age of 51.87 years) were included. Logarithm of the minimum angle of resolution (LogMar) best-corrected visual acuity increased from 0.39 ± 0.24 at baseline to 0.24 ± 0.22 at 3 months (p < 0.0001) and to 0.20 ± 0.07 at 6 months (p < 0.0001). Subretinal fluid decreased from 166.82 ± 111.11 micron at baseline to 52.33 ± 78.97 micron (p < 0.0001) at 3 months and 34.12 ± 67.56 micron at 6 months (p < 0.0001). The presence of a hot spot on fluorescein angiography and a focal choroidal hyperpermeability on indocyanine green angiography, but not the duration of symptoms correlated significantly with the resolution of subretinal fluid at month 3 (p = 0.023 and p = 0.001). Navigated micropulse laser laser treatment was found to be effective and safe for the treatment of chorioretinopathy, with significant improvement in visual and anatomical outcomes, unaccompanied by any adverse event at 3 and 6 months follow-up. Factors associated to subretinal fluid resolution may allow a better selection of likely responders to navigated micropulse laser treatment.

Type one macular neovascularization in central serous chorioretinopathy: Short-term response to anti-vascular endothelial growth factor therapy.

The aim of this study was to assess the short-term effect of anti-vascular endothelial growth factor (VEGF) treatment on type 1 macular neovascularization (MNV) secondary to central serous chorioretinopathy (CSCR) and to identify potential predictive factors for treatment response using multimodal imaging. Retrospective, multicentre study in CSCR patients with MNV detected by OCT-angiography and treated with anti-VEGF injections. Clinical and multimodal imaging data before and after anti-VEGF injections was reviewed. Univariate and multivariate linear regression analyses were performed to evaluate associations between the change in central macular thickness (CMT) after anti-VEGF therapy and other factors. Forty patients were included. One month after receiving a mean number of 2.7 anti-VEGF intravitreal injections, visual acuity increased significantly from 0.46 ± 0.3 logMAR at baseline to 0.38 ± 0.4 logMAR (p = 0.04). The CMT and foveal serous retinal detachment (SRD) decreased significantly from 330 ± 81.9 µm at baseline to 261.7 ± 63.1 µm after treatment (p < 0.001) and from 145.1 ± 98.8 µm at baseline to 52.6 ± 71.3 µm (p < 0.001), respectively. Subretinal fluid and/or intraretinal fluid were still present in 18 eyes (45%) one month after treatment. In the multivariate analysis, a higher SRD height was associated with a greater CMT change (p = 0.002) and a lower CMT change with the presence of subretinal hyperreflective material (SHRM) (p = 0.04). Fluid resorption was incomplete in about half of the patients with MNV secondary to CSCR after anti-VEGF injections. Shallower SRD or the presence of SHRM were predictors of poor response to anti-VEGF.

MP14-16 EFFICACY OF NIVOLUMAB PLUS IPILIMUMAB IN PRIMARY TUMOR AS FIRST-LINE THERAPY IN THE PATIENTS WITH ADVANCED RENAL CELL CARCINOMA

You have accessJournal of UrologyKidney Cancer: Advanced (including Drug Therapy) I (MP14)1 Sep 2021MP14-16 EFFICACY OF NIVOLUMAB PLUS IPILIMUMAB IN PRIMARY TUMOR AS FIRST-LINE THERAPY IN THE PATIENTS WITH ADVANCED RENAL CELL CARCINOMA Hiroshi Kikuchi, Takahiro Osawa, Ryuji Matsumoto, Takashige Abe, Satoru Maruyama, Toru Harabayashi, Haruka Miyata, Akira Kashiwagi, Ataru Sazawa, Riyo Fukui, Ken Morita, Ichiro Takeuchi, Noboru Yamashita, Keita Minami, Tango Mochizuki, and Nobuo Shinohara Hiroshi KikuchiHiroshi Kikuchi More articles by this author , Takahiro OsawaTakahiro Osawa More articles by this author , Ryuji MatsumotoRyuji Matsumoto More articles by this author , Takashige AbeTakashige Abe More articles by this author , Satoru MaruyamaSatoru Maruyama More articles by this author , Toru HarabayashiToru Harabayashi More articles by this author , Haruka MiyataHaruka Miyata More articles by this author , Akira KashiwagiAkira Kashiwagi More articles by this author , Ataru SazawaAtaru Sazawa More articles by this author , Riyo FukuiRiyo Fukui More articles by this author , Ken MoritaKen Morita More articles by this author , Ichiro TakeuchiIchiro Takeuchi More articles by this author , Noboru YamashitaNoboru Yamashita More articles by this author , Keita MinamiKeita Minami More articles by this author , Tango MochizukiTango Mochizuki More articles by this author , and Nobuo ShinoharaNobuo Shinohara More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001995.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: After the findings from CARMENA study, the role of cytoreductive nephrectomy (CN) should be considered in patient-tailored manner. Taking together with the new emergences of several effective combination therapies, the information of those effect on the primary site should be crucial for planning a future CN. This study aimed to focus exclusively on the size change of primary tumor following nivolumab plus ipilimumab (NivoIpi) treatment and elucidate the clinical factors associated with good response in primary tumor. METHODS: We retrospectively assessed 27 patients who were diagnosed with advanced renal cell carcinoma (RCC) and who had started NivoIpi. The changes in tumor size of the primary site were described using waterfall and spider plots. The parameters analyzed between responder and non-responder in the size of the primary tumor were International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk scores, peripheral blood markers and CRP. The ANOVA test was applied for the statistical analysis. RESULTS: The median age and follow-up periods were 66 years and 8.8 months, respectively. Nineteen patients were diagnosed with clear-cell renal cell carcinoma (ccRCC). Figure 1Ashow the maximum reduction from baseline in primary tumor and best overall response in ccRCC patients. Among ccRCC patients, 9 (47.4%) patients demonstrated significant response with 30% or more reduction from baseline within 4 months in primary tumors (Figure 1B). Of 6 patients who underwent nephrectomy, 3 patients whose primary tumors shrinked around 50-60% with reduction to 4 cm or less revealed no viable tumor cell in surgical specimens. Neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio tended to decrease in those responders compare to non-responders among ccRCC patients (P=0.0944 and P=0.0691). Platelet-to-lymphocyte ratio significantly decreased in those responders (P=0.0391). CONCLUSIONS: In our experience, significant responses of primary tumor were obtained with NivoIpi in half cases of ccRCC. Of note, inflammation markers were possible predictive factor for treatment response of primary tumor. Although further study is needed, these observations help us to consider CN from the viewpoint of the radiological and pathological aspects. Source of Funding: None declared © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e259-e259 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hiroshi Kikuchi More articles by this author Takahiro Osawa More articles by this author Ryuji Matsumoto More articles by this author Takashige Abe More articles by this author Satoru Maruyama More articles by this author Toru Harabayashi More articles by this author Haruka Miyata More articles by this author Akira Kashiwagi More articles by this author Ataru Sazawa More articles by this author Riyo Fukui More articles by this author Ken Morita More articles by this author Ichiro Takeuchi More articles by this author Noboru Yamashita More articles by this author Keita Minami More articles by this author Tango Mochizuki More articles by this author Nobuo Shinohara More articles by this author Expand All Advertisement Loading ...

Bone marrow plasma level of decorin may be associated with improved treatment outcomes in a subset of multiple myeloma patients

Decorin is a small leucine-rich proteoglycan rich in extracellular matrix with potential antitumor activity. However, the role of decorin in hematological malignancies remains unclear, especially in the case of multiple myeloma (MM), a bone marrow (BM) stroma-dependent plasma cell neoplasm. We measured decorin levels in BM plasma samples from 270 patients with newly diagnosed MM (NDMM) using enzyme-linked immunosorbent assays. Patients were divided into high decorin (H-DCN, > 18.99ng/mL) and low decorin (L-DCN <9.76ng/mL) groups. Patients in the H-DCN group had more advanced-stage disease, including more osteolysis terms of higher levels of C-terminal telopeptides of type I collagen (0.69±0.55 vs. 0.49±0.36ng/mL; P=0.028), than those in the L-DCN group. Decorin levels correlated positively with hepatocyte growth factor (HGF) levels in BM plasma samples from NDMM patients (Pearson correlation coefficient, 0.226; P<0.001). Patients with low HGF (<0.79ng/mL) but high decorin levels (≥12.95ng/mL) had a higher treatment response rate (90.5% vs. 54.5%, respectively; P=0.015) and improved overall survival (not reached vs. 53 months; P=0.0148) than those with lower decorin levels (<12.95ng/mL). Multivariate analysis confirmed that a high decorin level was an independent predictive factor for treatment response and survival in patients with low HGF levels. Our findings suggest that decorin may exert protective effects in this subset of MM patients.

Serum neutrophil/lymphocyte ratio as a potential predictor of treatment response for immune checkpoint inhibitors in patients with advanced hepatocellular carcinoma.

e16156 Background: Neutrophil to lymphocyte ratio (NLR) has been shown to associate with tumor progression. The present study was to investigate the role of NLR on predicting the treatment response for immune checkpoint inhibitors (ICIs) therapy in patients with advanced hepatocellular carcinoma (HCC). Methods: We retrospectively reviewed 81 patients received ICIs for advanced HCC from January 2017 to July 2019. We analyzed whether pre- and first 3 weeks post- treatment serum NLR level was associated with ICIs outcome. Results: In this study, the pre-treatment NLR level ranged from 0.64 to 14.93 among 81 patients. The cut-off level of NLR was set as the median value of 2.79. The objective response rate (ORR) in the patients with NLR＜2.79 (low NLR) was 25.0%, which was significantly better than that of patients with NLR ≥2.79 (high NLR) (7.3%, P ＝0.03). Compared to patients with high NLR, patients with low NLR exhibited significantly longer median progression-free survival (PFS) (3.7 vs 3.0 months, P ＝0.004) and median overall survival (OS) (10.3 vs 7.5 months, P ＝0.001). Multivariate analysis revealed high NLR was an independent unfavourable prognostic factor for PFS (hazard ratio [HR] = 1.857, 95% confidence interval [CI] = 1.093-3.154; P = 0.022) and OS (HR = 2.267, 95% CI = 1.221-4.207; P = 0.009). For the patients with high pre-treatment NLR level, ICIs outcome was stratified more clearly by first 3 weeks post- treatment NLR level. Conclusions: The pre- and first 3 weeks post- treatment serum NLR level could be considered as a predictive factor of treatment response for ICIs in patients with advanced HCC.

Prognostic factors of cyclosporine A combined with danazol with or without thalidomide in myelodysplastic syndrome treatment with low-percentage bone marrow blasts

目的探讨环孢素A（CsA）联合达那唑±沙利度胺治疗原始细胞不增高骨髓增生异常综合征（MDS）疗效及其影响因素。方法收集2011年12月至2019年12月在中国医学科学院血液病医院确诊且接受CsA联合达那唑±沙利度胺治疗的115例原始细胞不增高初诊原发性MDS患者临床资料，回顾性分析其临床特征、疗效及疗效影响因素，并建立疗效预测模型。结果55例（47.8％）患者获得治疗反应，其中11例获得完全缓解，44例获得血液学改善［红系反应率为49.5％（52/105），血小板反应率为40.7％（35/86），中性粒细胞反应率为35.0％（14/40）］。29例红细胞输注依赖的患者中7例（24.1％）脱离输血依赖。总体中位疗效持续时间为20（3～84）个月。单因素分析显示年龄<60岁较≥60岁患者疗效好（52.5％对22.2％，P＝0.018），而伴红细胞输注依赖较非红细胞输注依赖患者（24.1％对55.8％，P＝0.003）、U2AF1突变型患者较U2AF1野生型患者（26.1％对53.2％，P＝0.020）疗效差。多因素分析显示年龄<60岁（OR＝4.302, 95％CI 1.245～14.820，P＝0.021）、无红细胞输注依赖（OR＝3.774，95％CI 1.400～10.177，P＝0.009）和无U2AF1突变（OR＝3.414，95％CI 1.168～9.978，P＝0.025）均为获得血液学改善的独立预后因素。联合上述影响疗效的独立预后因素建立疗效预测模型，具有0、1、2、3个危险因素患者的总有效率分别为65％、30％～35％、10％～15％、3％。结论CsA联合达那唑±沙利度胺可有效改善原始细胞不增高MDS患者的血细胞减少症状。年龄<60岁、不伴红细胞输注依赖且无U2AF1突变患者治疗反应较好。

Association between ADAMTS13 activity-VWF antigen imbalance and the therapeutic effect of HAIC in patients with hepatocellular carcinoma.

BACKGROUNDPrediction of HAIC treatment response is important for improving the prognosis in patients with hepatocellular carcinoma (HCC). The progression of HCC is related to hypercoagulability and angiogenesis. It is known that ADAMTS13 and von Willebrand factor (VWF) are related to hypercoagulability. In addition, previous study reported that the association between ADAMTS13 and VWF, and angiogenesis via vascular endothelial growth factor (VEGF). Recently, ADAMTS13 and VWF have been associated with the prognosis in patients with various kinds of cancer undergoing chemotherapy.AIMTo investigate whether ADAMTS13 and VWF become useful biomarkers of treatment response in HCC patients before the initiation of HAIC treatment.METHODSSeventy-two patients were enrolled in this study. ADAMTS13 activity (ADAMTS13:AC), VWF antigen (VWF:Ag) and VEGF levels were determined via enzyme-linked immunosorbent assay. Univariable and multivariable analyses were performed to determine the predictive factors of treatment response in patients with HCC undergoing HAIC treatment.RESULTSADAMTS13:AC levels in HCC patients with stable disease (SD) + partial response (PR) of HAIC treatment were significantly higher than those with progressive disease (PD) (P < 0.05). In contrast, VWF:Ag/ADAMTS13:AC ratio and VEGF levels in HCC patients with SD + PR were significantly lower than those with PD (both P < 0.05). Patients with high VWF:Ag/ADAMTS13:AC ratio (> 2.7) had higher VEGF levels than those with low ratio (≤ 2.7). Multivariable analysis revealed that VWF:Ag/ADAMTS13:AC ratio was a predictive factor of HAIC treatment response.CONCLUSIONVWF:Ag/ADAMTS13:AC ratio may become a useful biomarker of treatment response in HCC patients before the initiation of HAIC treatment.

Efficacy and safety of keishibukuryogan, a traditional Japanese Kampo medicine, for hot flashes in prostate cancer patients receiving androgen deprivation therapy.

BackgroundThe efficacy and safety of keishibukuryogan, a traditional Japanese medicine, were investigated for the treatment of hot flashes in prostate cancer (PC) patients receiving androgen deprivation therapy.MethodsThirty patients were enrolled and orally administered 2.5 g keishibukuryogan three times daily for 12 weeks. The frequency, strength, and duration of hot flashes were self-evaluated by the patients in a diary every 4 weeks. All patients also completed a questionnaire to determine their aging male symptoms (AMS) scale score and underwent blood biochemical testing.ResultsTwenty-five patients completed the 12-week treatment. Hot flash strength significantly improved 4, 8, and 12 weeks after treatment. Their frequency was significantly reduced at the 8-week visit, and duration was significantly shorter after the 8-week visit. In addition, the score of the AMS somatic subscale was improved at the 8- and 12-week visits. Among the somatic items, questions 3 (excessive sweating) and 5 (increased need for sleep) were significantly improved. Obesity, radiation, and a longer duration of PC were predictive factors for treatment response. Prostate specific antigen and total testosterone levels were unchanged, and no patients had severe adverse effects.ConclusionsKeishibukuryogan was an effective and safe treatment for hot flashes in PC patients.

Comprehensive Genomic Profile of Heterogeneous Long Follow-Up Triple-Negative Breast Cancer and Its Clinical Characteristics Shows DNA Repair Deficiency Has Better Prognostic.

Triple-negative breast cancer (TNBC) presents a marked diversity at the molecular level, which promotes a clinical heterogeneity that further complicates treatment. We performed a detailed whole exome sequencing profile of 29 Mexican patients with long follow-up TNBC to identify genomic alterations associated with overall survival (OS), disease-free survival (DFS), and pathologic complete response (PCR), with the aim to define their role as molecular predictive factors of treatment response and prognosis. We detected 31 driver genes with pathogenic mutations in TP53 (53%), BRCA1/2 (27%), CDKN1B (9%), PIK3CA (9%), and PTEN (9%), and 16 operative mutational signatures. Moreover, tumors with mutations in BRCA1/2 showed a trend of sensitivity to platinum salts. We found an association between deficiency in DNA repair and surveillance genes and DFS. Across all analyzed tumors we consistently found a heterogeneous molecular complexity in terms of allelic composition and operative mutational processes, which hampered the definition of molecular traits with clinical utility. This work contributes to the elucidation of the global molecular alterations of TNBC by providing accurate genomic data that may help forthcoming studies to improve treatment and survival. This is the first study that integrates genomic alterations with a long follow-up of clinical variables in a Latin American population that is an underrepresented ethnicity in most of the genomic studies.

Flow signal change in polyps after anti-vascular endothelial growth factor therapy.

Optical coherence tomography angiography (OCTA) is a novel, non-invasive imaging tool used to detect vascular flow. The absence of a flow signal in OCTA in polyps revealed by indocyanine green angiography (ICGA) in patients with polypoidal choroidal vasculopathy (PCV) may indicate slow or compromised filling of blood flow from choroidal vessels. Naïve patients with PCV treated with intravitreal injections of aflibercept (IVI-A) were enrolled in this study to validate the hypothesis that baseline flow may affect the outcome of polyp regression in ICGA. The flow signal of polyps in OCTA was detected by manual segmentation in the corresponding location by ICGA. Polyps were defined as high-flow if both OCTA and ICGA showed positive findings, and low-flow if OCTA showed a negative flow signal in 3 consecutive horizontal scans at the polyp area shown in ICGA. A total of 24 polyps were identified in 13 PCV patients at baseline. Of these 24 polyps, 22 (91.7%) were high-flow and 2 (8.3%) were low-flow. After 3 monthly IVI-A, all low-flow polyps had complete regression in ICGA. Among 17 (77%) high-flow polyps at baseline that had regression after treatment, 10 (58.8%) became low-flow, while 5 (22.7%) persistent polyps remained high-flow. Flow signal of polyps as detected by OCTA could be a predictive factor for treatment response in patients with PCV. Monitoring changes in flow signal after treatment is clinically relevant.

SBRT For Head and Neck Skin Cancer: An Initial Experience in 106 Medically Unfit Patients

Stereotactic Body Radiation Therapy (SBRT) is an alternative treatment strategy for patients with head and neck skin cancer (HNSC) unable to undergo a protracted radiotherapy course. We report outcomes of SBRT for HNSC patients treated at a tertiary high-volume institution. A retrospective review of patients who received SBRT from 2012-2019 was conducted. Kaplan-Meier method was used to estimate the one-year local control (LC), locoregional control (LRC) outside of SBRT field, overall survival (OS), progression-free survival (PFS) and late toxicity (LT) rates from time of SBRT completion. Univariate and multivariate Cox proportional hazard models were performed. Acute and late grade 3 and 4 toxicity were reported according to the Common Terminology Criteria for Adverse Events v4.0. A total of 106 patients were identified with 112 lesions treated. The cohort consisted of patients treated for primary (n = 51), nodal (n = 47) and both primary and nodal disease (n = 8). The T and N categories prior to SBRT were Tx-2: n = 78, T3-4: n = 28; N0-1: n = 67, N2-3: n = 39. Median age at diagnosis was 84 years with median ECOG performance status of 2. HNSC histologies included cutaneous squamous cell carcinoma (n = 77), basal cell carcinoma (n = 14), melanoma (n = 8), Merkel cell carcinoma (n = 6), and 1 unconfirmed. Fractionation schemes ranged from 32-50 Gy in 4-6 fractions, with the most common regimens being 45 Gy in 5 fractions [52% (n = 55)] and 40 Gy in 5 fractions [32% (n = 34)]. Median gross tumor volume (GTV) was 31 cm3 (17-56) and mean planning tumor volume (PTV) dose was 44 Gy. Median follow-up was 8 months and actuarial median OS was 14 months. The one-year LC, LRC outside of SBRT field, OS, PFS and LT rates were 78% (69-88), 72% (62-84), 53% (43-65), 52% (40-62), and 25% (16-38), respectively. Larger GTVs were associated with reduced PFS [HR 1.58, p = 0.004], OS [HR 1.37, p = 0.039], and LRC outside of SBRT field [HR 1.83, p = 0.006] but not LC [HR 0.87, p = 0.50]. Multivariable models revealed that larger GTVs [HR 1.47, p = 0.046] and higher biologically effective dose (BED10) [HR 1.05, p = 0.03] were associated with a higher rate of late toxicity. There was no statistical difference between proportions of grade ≥3 acute (p = 0.22) and late toxicities (p = 0.37) in patients treated with doses ≤40 Gy vs. >40 Gy. For acute toxicity, 41 patients had grade 3, and 1 had grade 4. The most common acute toxicity was dermatitis (n = 39). Twenty-eight patients (26%) experienced ≥ late grade 3 toxicity, with the most common being fibrosis (n = 19) and soft tissue ulceration (n = 6). No grade 5 toxicity was observed. SBRT in HNSC provides durable disease control with acceptable toxicity for select medically unfit patients unable to undergo extended radiotherapy courses. Predictive factors of treatment response and toxicity include GTV and BED10. Further prospective studies including quality of life measures and dosimetric correlations with larger cohorts are needed.

Efficacy of orbital radiotherapy in moderate-to-severe active graves\u2019 orbitopathy including long-lasting disease: a retrospective analysis

BackgroundWe aimed to explore the efficacy of orbital radiotherapy (RT) in patients with moderate-to-severe active Graves’ orbitopathy (GO), including long-lasting disease, and to determine the predictive factors associated with treatment response.MethodsThis was a retrospective study of 62 moderate-to-severe active GO patients treated with RT. Demographic data and ophthalmic findings prior to RT and at 3 and 6 months afterward were analyzed. Computed tomography was performed before and after RT to compare orbital volume change. We used logistic regression to determine the predictive factors for treatment response. Subjects were divided into early- and late-active phase groups based on GO duration of 24 months and treatment outcomes were compared with each other to observe the effects of RT timing on treatment response.ResultsForty (64.5%) and forty-six (74.1%) patients experienced improvements in GO at 3 and 6 months after radiotherapy, respectively. Ocular parameters such as clinical activity score (CAS), proptosis, extraocular muscle (EOM) limitation, and compressive optic neuropathy (CON) were improved by RT. Volumes of EOM significantly decreased after RT. The enlargement of EOMs and EOM limitation were predictive factors for a good response to RT. At 6 months after RT, 22 (68.8%) patients of late-active phase group exhibited improvement in GO, which is comparable to the number of 24 (80.0%) patients of early-active phase group. In the late-active phase group, CAS, diplopia, and visual acuity were improved significantly, but there was no change in EOM limitation.ConclusionsIn moderate-to-severe active GO patients, orbital RT may help improve high CAS, proptosis, EOM limitation, and CON. The orbital RT in long-lasting active GO patients may be considered as treatments for the relief of symptoms including high CAS and poor visual acuity.