Pretreatment Hemoglobin Research Articles

A Multicenter Retrospective Cohort Study Assessing the Incidence of Anemia in Patients Associated With Uterine Fibroids.

Uterine fibroids are benign tumors that develop from the smooth muscle tissue of the uterus, typically during a woman's reproductive years. A substantial proportionof women with uterine fibroids exhibit symptoms, including menorrhagiathat considerably compromise theirquality of life. This study aims to characterizethe fibroid subtype most commonly associated with the incidence ofanemia. This retrospective multi-center cohort study investigated the incidence of anemia in premenopausal women who were diagnosed with uterine fibroids between January 2016 and December 2022. Fibroid position, size, location, and number were assessed by trans-abdominal/vaginal ultrasound and hysteroscopy and correlated to the pre-treatment hemoglobin level. Three-quarters of patients (n=6) with submucosal fibroid presented with any form of anemia followed by 59.3% (n=115) of patients with intramural fibroid and only 36.8% (n=25) of patients with sub serousal fibroid. Interestingly, there was no difference between the groups with regard to the severity of anemia at presentation. Most red blood cells (RBCs) and hemoglobin (Hb) indices were comparable between the groups, except for mean corpuscle volume (MCV) as it was significantly lower in patients with intramural fibroids. Moreover, our investigations showed that the submucosal fibroids tend to present in a higher number as well as the biggest in size. The multivariable logistic regression showed that subserosal fibroids are associated with the lowest risk of developing anemia. In conclusion, our results suggest that the occurrence of anemia should always be considered in women with submucosal fibroids. However, after adjusting for other contributing factors such as menorrhagia, submucosal fibroid did not show an increase in the risk of anemia.

Feasibility, Safety, and Factors Predicting Completion of CROSS Protocol–Based Neoadjuvant Chemoradiotherapy for Esophageal Squamous Carcinoma: Experience from an Indian Tertiary Care Cancer Center

Background Neoadjuvant chemoradiotherapy (NACRT) using the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) protocol has improved esophageal cancer outcomes. This study reports the real-world experience of the CROSS regimen for esophageal squamous cell carcinoma (ESCC) regarding its feasibility, safety, and predictors of treatment completion from an Indian tertiary center. Methodology A retrospective review was conducted for patients with ESCC receiving CROSS (radiation dose: 41.4 Gy) or a modified CROSS (mCROSS; radiation dose: 45 Gy) protocol NACRT between 2015 and 2022. We studied the treatment tolerability, factors predicting NACRT completion, and the effect of completion of its chemotherapy component on the pathological outcomes. Results Of the109 patients (68.8% males; mean age, 56 ± 9 years; Charlson's comorbidity index [CCI] >2, 19.3%; stage III–IVA, 58%; mean tumor length, 5.5 ± 2.1cm; CROSS, 70.6%; mCROSS, 29.4%), all except 4 completed radiotherapy but only 58 (53.2%) patients completed ≥4 cycles of chemotherapy. Forty-nine patients belonged to the “extended” CROSS trial inclusion criteria. Among the 60 patients who fulfilled the CROSS inclusion criteria, only 51.7% were able to complete ≥4 chemotherapy cycles. The commonest reason for noncompletion of chemotherapy was the occurrence of neutropenia (60.8%). Pretreatment hemoglobin (≥12 vs. <12 g%; odds ratio [OR]: 2.76; 95% confidence interval [CI]: 1.10–6.96; p = 0.031), a low CCI (≤2 vs. >2; OR: 2.98; 95% CI: 1.02–8.73; p = 0.047), and radiation therapy techniques (conformal vs. conventional; OR: 3.29; 95% CI: 1.14–9.50; p = 0.028) were associated with completion of chemotherapy (≥4 cycles). Although there was a trend toward improved R0 resection (95.7 vs. 91.4%), reduced node positivity (17.0 vs. 31.4%), and a high pCR (57.4 vs. 48.6%) in patients completing chemotherapy (≥4 cycles) compared with those not completing chemotherapy (<4 cycles), these differences were statistically nonsignificant. Conclusion In this study, ESCC patients receiving the CROSS protocol NACRT could complete their radiotherapy component, but a significant proportion exhibited poor chemotherapy tolerance. Neutropenia was a major factor limiting chemotherapy delivery, but anemia, high CCI, and conventional radiation techniques were also associated with noncompletion of chemotherapy. The omission of a few chemotherapy cycles had no significant effect on the pathological response; however, its impact on cancer survival requires further evaluation.

External validation of hemoglobin and neutrophil levels as predictors of the effectiveness of ipilimumab plus nivolumab for treating renal cell carcinoma.

Pretreatment hemoglobin and neutrophil levels were previously reported to be important indicators for predicting the effectiveness of ipilimumab plus nivolumab (IPI + NIVO) therapy for renal cell carcinoma (RCC). Therefore, we aimed to validate this in a large external cohort. In total, 172 patients with RCC who underwent IPI + NIVO treatment at a multicenter setting were divided into three groups according to their pretreatment hemoglobin and neutrophil levels (group 1: non-anemia; group 2: anemia and low-neutrophil; and group 3: anemia and high-neutrophil). Group 1 showed better survival than groups 2 and 3 (overall survival: 52.3 vs. 21.4 vs. 9.4 months, respectively; progression-free survival: 12.1 vs. 7.0 vs. 3.4 months, respectively). In this large cohort, we validated our earlier observation that hemoglobin and neutrophil levels can be reliable predictors of the effectiveness of IPI + NIVO in advanced RCC. Thus, our approach may aid in selecting the optimal first-line therapy for RCC.

Nomogram for Predicting Survival in Locally Advanced Cervical Cancer with Concurrent Chemoradiotherapy plus or Not Adjuvant Chemotherapy: A Retrospective Analysis Based on 2018 FIGO Staging.

Background: The comprehensive treatment mode of combining concurrent chemoradiotherapy (CCRT) with adjuvant chemotherapy (AC) is a commonly used mainstream model in the clinical practice of locally advanced cervical cancer (LACC). However, the necessity for AC after CCRT lacks sufficient evidence-based medical support. This study constructs a predictive model for the survival time dependence of CCRT ± AC for LACC based on the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging with internal validation, the prognosis was assessed with intensity-modulated radiotherapy (IMRT) and concurrent cisplatin, and provides guidance for future stratified treatment. Materials and Methods: The retrospective analysis included 482 patients with LACC who CCRT from January 2016 to January 2023. Patients who used the 2009 FIGO staging were all standardized for the 2018 FIGO staging. The 482 patients with LACC were divided into a training set (n = 290) and a validation set (n = 192) at a ratio of 6:4. COX multivariate regression model and LASSO regression were used to screen for independent prognostic factors affecting progression-free survival (PFS) and overall survival (OS), and a nomogram clinical prediction model was constructed based on these factors. Evaluate the effectiveness of the model through the receiver operating characteristic curve, calibration curve, decision curve, risk heat map, and survival curves for risk stratification. Results: The PFS and OS independent prognostic risk factors affecting the 2018 FIGO staging of LACC during CCRT were validated to be similar to the 2009 FIGO staging prediction model reported in previous literature. In the training cohort, area under the curve (AUC) values at 1, 3, and 5 years were 0.941, 0.882, and 0.885 for PFS, and 0.946, 0.946, and 0.969 for OS, respectively. When applied to a test cohort, the model also showed accurate prediction result (AUC at 1, 3, and 5 years were 0.869, 0.891, and 0.899 for PFS, and 0.891, 0.941 and 0.878 for OS, respectively). Subgroup analysis suggests that patients with LACC, adenocarcinoma, stage IVA, pelvic lymph node metastasis, pretreatment hemoglobin ≤100 g/l and residual tumor diameter >2 cm, who received CCRT in the 2018 FIGO stage, may benefit more from adjuvant chemtherapy. Conclusions: Based on the 2018 FIGO staging, a nomogram prediction model for PFS and OS in patients with LACC undergoing CCRT was developed. The model, established by combining weighted clinical and pathological factors, can provide more personalized treatment predictions in clinical practice. For patients with high-risk factors such as residual tumor diameter > 2 cm after CCRT for LACC, AC may bring benefits.

Apparent diffusion coefficient values predict response to brachytherapy in bulky cervical cancer

BackgroundDiffusion-weighted magnetic resonance imaging (DWI) provides a measurement of tumor cellularity. We evaluated the potential of apparent diffusion coefficient (ADC) values obtained from post-external beam radiation therapy (EBRT) DWI and prior to brachytherapy (BT) to predict for complete metabolic response (CMR) in bulky cervical cancer.MethodsClinical and DWI (b value = 500 s/mm2) data were obtained from patients undergoing interstitial BT with high-risk clinical target volumes (HR-CTVs) > 30 cc. Volumes were contoured on co-registered T2 weighted images and 90th percentile ADC values were calculated. Patients were stratified by CMR (defined by PET-CT at three months post-BT). Relation of CMR with 90th percentile ADC values and other clinical factors (International Federation of Gynecology and Obstetrics (FIGO) stage, histology, tumor and HR-CTV size, pre-treatment hemoglobin, and age) was assessed both in univariate and multivariate logistic regression analyses. Youden’s J statistic was used to identify a threshold value.ResultsAmong 45 patients, twenty-eight (62%) achieved a CMR. On univariate analysis for CMR, only 90th percentile ADC value was significant (p = 0.029) while other imaging and clinical factors were not. Borderline significant factors were HR-CTV size (p = 0.054) and number of chemotherapy cycles (p = 0.078). On multivariate analysis 90th percentile ADC (p < 0.0001) and HR-CTV size (p < 0.003) were highly significant. Patients with 90th percentile ADC values above 2.10 × 10− 3 mm2/s were 5.33 (95% CI, 1.35–24.4) times more likely to achieve CMR.ConclusionsClinical DWI may serve to risk-stratify patients undergoing interstitial BT for bulky cervical cancer.

Weight loss induced by a hypocaloric diet with or without fish oil supplementation re-established iron and omega-3 fatty acid homeostasis in middle-aged women with obesity: A post-hoc analysis of a randomized controlled trial

ObjectiveMiddle-aged women with obesity are at increased risk of iron overload and iron disorder is known to disrupt n-3 polyunsaturated fatty acid homeostasis. We evaluated relationships between pretreatment hemoglobin and n-3 polyunsaturated fatty acid levels, and tested whether pretreatment hemoglobin contributed to inter-individual variability in weight loss with special focus on changes in body weight, iron and n-3 polyunsaturated fatty acid profiles. Study design117 middle and older aged women with obesity and more than two metabolic abnormalities were randomized to a 12-week hypocaloric diet without or with fish oil supplementation. Blood iron biomarker and erythrocyte membrane phospholipid profiles were evaluated. Main outcomeThe absolute change from baseline to week 12 in serum iron and erythrocyte n-3 polyunsaturated fatty acid levels according to pretreatment hemoglobin tertiles and fish oil supplementation. ResultsA Pearson correlation analysis showed that pretreatment hemoglobin levels were negatively correlated with linoleic acid (r = −0.231), α-linoleic acid (r = −0.279), and n-3 polyunsaturated fatty acid (r = −0.217) (all p < 0.05). Dietary weight loss markedly enhanced erythrocyte membrane lipids of linoleic acid, α-linoleic acid, and n-6 and n-3 polyunsaturated fatty acid only in those women with the highest pretreatment hemoglobin levels (tertile 3) (all p < 0.05). Fish oil supplementation increased bioavailable iron in women with moderate pretreatment hemoglobin levels (tertile 2) (p < 0.05) and, to a lesser extent, prevented a reduction in circulating iron in those with the lowest hemoglobin levels (tertile 1). ConclusionDietary weight loss is an effective treatment program to manage obesity-related iron and n-3 polyunsaturated fatty acid disorders, particularly for middle-aged women with obesity and iron overload.

Mean Rise in Hemoglobin After Intravenous Iron Therapy in Children with Iron Deficiency Anemia

Introduction: Iron deficiency anemia (IDA) is a significant public health issue in Pakistan, affecting up to 63% of children, as revealed by the Pakistan National Nutritional Survey 2018. While oral iron remains the primary choice, challenges in compliance have led to the consideration of intravenous (IV) iron therapy, particularly iron sucrose. The study discusses the safety and efficacy of IV iron therapy in Pakistani children and aims to broaden our understanding of treating IDA in resource-constrained regions. Aims &amp; Objectives: To determine the average hemoglobin (Hb) increase in iron-deficient-anemic children aged 01 to 12 years after treatment with intravenous iron sucrose. Place and Duration of Study: A quasi-experimental study was undertaken at Fauji Foundation Hospital in Rawalpindi, spanning from September 2021 to September 2022. Material &amp; Methods: The study focused on a cohort of pediatric patients aged between 1 and 12 years, all of whom were diagnosed with iron deficiency anemia and had previously encountered ineffective outcomes with oral iron therapy. In this investigation, the patients received treatment involving intravenous iron sucrose. Subsequently, their progress was diligently monitored after a period of 8 weeks. Improvement in hemoglobin level was assessed at the end of treatment to evaluate its efficacy.Data processing and statistical analysis were carried out using SPSS version 23,p-value of &lt;0.05 indicated statistical significance. Results: Out of 150 study cases, 96 (64.0 %) were male, while 54 (36.0 %) were female. The mean age of our study cases was 05 ± 2.3 years of these 150 study cases, 74 (49.3 %) belonged to rural areas, and 76 (50.7 %) belonged to urban areas. Poor socioeconomic status was noted in 97 (64.7 %), and 53 (35.3%) were middle-income. A family history of iron deficiency anaemia was recorded in 16 (10.7%). Iron deficiency due to dietary iron insufficiency was reported in 67 (44.7%), Total Parentral Nutrition (TPN) dependencywas seen in 61 (40.7%) and 22 (14.7%) had chronic gastritis. The mean baseline (pretreatment) haemoglobin level was 7.71 ± 0.63 g/dl, while the mean post-treatment haemoglobin level was 10.68 ± 0.60 g / dl (p = 0.001). Conclusion: After intravenous iron sucrose, we noted a significant rise in paediatric patients' hemoglobin levels, emphasizing its effectiveness and safety. Statistically, we found correlations with age, family history, and causes. Healthcare practitioners should consider injectable iron treatments for better results and reduced health issues in this group.

The prognostic value of ductal adenocarcinoma of the prostate in patients with advanced prostate cancer treated with abiraterone acetate.

167 Background: Previous studies have indicated that ductal adenocarcinoma of the prostate (DA) is associated with adverse prognosis in patients with localized prostate cancer (PCa). However, the clinical significance of DA in advanced PCa remains largely ambiguous. This study endeavors to investigate the relationship between the existence of DA in prostate biopsy specimens and treatment outcomes among patients with advanced PCa receiving abiraterone acetate (AA) therapy. Methods: We retrospectively analyzed data from 440 patients with advanced PCa who received AA at either the metastatic hormone-sensitive (mHSPC, N=123) or castration-resistant PCa (mCRPC, N=317) stage. The presence of DA and its proportion was evaluated based on prostate biopsy specimens. Kaplan-Meier curves and COX regression were used to evaluate the predictive significance of DA on AA efficacy, including PSA response, PSA progression-free survival (PSA-PFS), and radiographic progression-free survival (rPFS). Results: In aggregate, DA was detected in 35/440 (8.0%) patients, with 13/440 (3.0%) and 22/440 (5.0%) men harboring DA&lt;5% and ≥5%, respectively, in the total tumors. The overall PSA response rate in the entire cohort was 302/440 (68.6%), and it was comparable for people with and without DA, with both groups having a response rate of 68.6%. Of note, compared with patients without DA, men with DA have significantly longer median PSA-PFS (mPSA-PFS, 12.1- vs. 25.0-Mo, P=0.005) and median rPFS (mrPFS, 19.8 vs. 38.2-Mo, P=0.034). Subgroup analysis based on DA proportion further revealed that in comparison with PCa without DA, DA≥5% was an indicator of favorable PSA-PFS (HR, 95%CI: 0.28, 0.14-0.56, p&lt;0.001) and rPFS (HR, 95%CI: 0.35, 0.18-0.72, p=0.004), while DA&lt;5% was not. In multivariate COX regression analysis, after adjusting by clinicopathological factors, including mCRPC/mHSPC stage, ISUP grading, metastatic burden, pain score and pretreatment hemoglobin, alkaline phosphatase, and lactate dehydrogenase, DA≥5% was still independently associated with better therapeutic efficacy of AA treatment (PSA-PFS: HR, 95%CI: 0.36, 0.17-0.74, p&lt;0.001; rPFS: HR, 95%CI: 0.47, 0.23-0.96, p=0.040). Conclusions: A DA proportion ≥5% in the tumor is related to improved treatment efficacy for individuals with advanced PCa receiving AA. Thus, in the pathological diagnosis of PCa, it is necessary to routinely report the presence and proportion of DA in order to aid with treatment decision-making.

Hemolytic anemia associated with intravenous immunoglobulin in Kawasaki disease

BackgroundThe administration of high-dose intravenous immunoglobulin (IVIG) is a standard treatment for the management of Kawasaki disease (KD). IVIG is known to be a highly effective and safe treatment.Case presentationWe report the development of hemolytic anemia in seven children receiving repeated doses of IVIG. The children were aged 3–44 months and included 4 girls and 3 boys. All children received 10% IVIG and a second course of immunoglobulin because they did not respond to the first course of immunoglobulin. Two received high-dose aspirin (50 mg/kg), and five received low-dose aspirin (5 mg/kg). Two patients required additional methylprednisolone pulse therapy (30 mg/kg) after the second dose of immunoglobulin, and three patients received oral prednisolone therapy for defervescence. Three patients showed coronary artery dilation during hospitalization and normalized within two months. Pretreatment hemoglobin averaged 11.3–14.2 g/dL, and post-hemolytic anemia hemoglobin ranged from 7.4 to 9.6 g/dL, with a difference of 1.7–6.8 g/dL. Reticulocytes were increased to 3.3–13.2%. Peripheral blood smears showed normochromic normocytic anemia, and anisopoikilocytosis. All children were positive for warm-type antibodies with IgG+, C3d- in direct antiglobulin test, and the blood group was A + in five and B + in two. None of the patients received immunomodulatory therapy or red blood cell transfusions. They were followed for a year and all recovered.ConclusionEspecially, in non-O blood group KD patients who are refractory to initial IVIG and require a second dose of IVIG or 10% formulation the possibility of immune hemolytic anemia should be carefully considered, and close follow-up should be maintained after therapy.

Hemoglobin level and survival in cervical cancer with chemoradiotherapy at high altitude, 2020-2022.

The purpose of this retrospective study was to determine the prognosis of altitude and pre-treatment hemoglobin (Hb) levels with progression-free survival (PFS) among women from the jungle and Andean regions of Peru with cervical cancer (CC) receiving weekly cisplatin and concurrent radiotherapy followed by brachytherapy or teletherapy boost. Patients with advanced clinical stage II-IVA CC were grouped according to Hb level (≥ 12.0, 11.9-10.0, 9.9-9.0 and ≤ 8.9 g/dL). Outcome measures were PFS, overall survival and local PFS. Between 1/2020 and 12/2022, 159 patients contributed demographic, clinical, pre-treatment Hb and outcome data with a median follow-up of 38 months. Kaplan-Meier estimates for survivals according to pre-treatment Hb level were significant when compared to a level of ≤8.9 g/dL, while estimates with altitude did not show statistical significance. Cox regression analysis of PFS demonstrated that pre-treatment Hb levels ≤8.9 g/dL (p = 0.000) were a significant factor. Age (p = 0.023), stage (p = 0.000), tumour size (p = 0.006) and treatment duration (p = 0.000) were also significant in the regression model. There is no difference between altitude and survival, but the difference in pre-treatment Hb level was a prognostic indicator of survival, with a Hb level of ≤8.9 g/dL being the worst prognosis.

Predictors of Myelosuppression for Patients with Head and Neck Squamous Cell Carcinoma After Induction Chemotherapy.

Induction chemotherapy (ICT) has become an initial treatment for head and neck squamous cell carcinoma (HNSCC). However, myelosuppression, an unavoidable side effect of ICT, significantly impacts follow-up treatment and prognosis. The main objective of this study is to identify the risk factors and predictors of myelosuppression and its different severity after ICT for ICT. We retrospectively reviewed medical records of 102 patients with hypopharyngeal cancer or oropharyngeal cancer who received initial ICT from 2013 to 2022. Univariate and multivariate logistic regression analyses were performed to identify risk factors for myelosuppression. Receiver-operating characteristic (ROC) curves were generated using the results of multiple logistic regression analysis to identify data with the highest sensitivity and lowest false-negative rate. Pretreatment lymphocyte count (PLC) and the pretreatment platelet count (PPC) were identified as independent risk factors of myelosuppression (P < .05). Pretreatment hemoglobin count (PHC) was an independent risk factor for predicting myelosuppression in patients with grades III to IV disease. Patients with myelosuppression after ICT are more sensitive to chemotherapy. The PLC and PPC predicted myelosuppression in patients with HNSCC-administered ICT, and the PHC predicted grades III to IV myelosuppression. Myelosuppressed patients were more chemosensitive after ICT.

Blood Biomarkers and Risk of Venous Thromboembolism in Cancer Patients: A Systematic Review and Meta-Analysis

Patients with cancer have an increased risk of venous thromboembolism (VTE). Currently, several VTE risk prediction tools have been developed to identify candidates for primary VTE thromboprophylaxis. However, the availability of reliable and highly discriminatory prediction models for VTE risk assessment in cancer patients is limited, warranting further improvement of VTE risk stratification strategies. The implementation of biomarkers in risk assessment models might lead to refined VTE risk prediction, but it remains to be more comprehensively investigated. In this systematic review and meta-analysis, we aimed to evaluate and summarize all candidate biomarkers and their association with cancer-associated VTE. We conducted an electronic search in Medline, EMBASE and Cochrane central databases for studies that evaluated biomarkers in adult patients with cancer from inception to September 26 th 2022. We included observational and interventional studies reporting on subsequent VTE occurring after a cancer diagnosis. The baseline or index event of the biomarker measurements had to be definitively and uniformly applied to all enrolled patients. Two reviewers independently screened titles, abstracts and full-text articles for inclusion. Median differences (for continuous measures) and Odds Ratios (OR) (for dichotomous cut-off measures) with 95% confidence intervals (95% CI) were estimated and pooled using random-effects models. We assessed each studies risk of bias using the Quality in Prognostic Studies (QUIPS) risk of bias tool. Our search identified 4274 studies that were screened for inclusion (Figure 1). Following the screening, 109 studies (with 520 biomarker measurements) met the inclusion criteria and were included in the systematic review. Of these, 51 studies (with 174 biomarker measurements) were included in the meta-analysis. The majority of the studies were cohort studies (n=47; 32 prospective and 15 retrospective), while the other 4 studies were nested case-control studies. Eighteen studies had a study population of mixed cancer types and the remaining studies had a study population of specific cancer types, including: lung (n=6), gynecologic (n=5), breast (n=3), stomach (n=3), lymphoma (n=2), myeloma (n=2), ovarian (n=2), pancreas (n=2), brain (n=1), colorectal (n=1), gastrointestinal (n=1), genitourinary (n=1), gynecologic or breast (n=1), head and neck (n=1), liver (n=1), and prostate (n=1). We calculated the median difference and 95% CI for 23 different biomarkers. Cancer patients who experienced subsequent VTE events had significantly higher pre-treatment factor VIII activity, peak thrombin, platelet count and prothrombin fragment F1+2 levels compared to patients who did not experience VTE events (Table 1). Pre-treatment d-dimer levels were also higher in cancer patients who developed VTE, however, considerable heterogeneity was observed (Table 1). Contrastingly, pre-treatment hemoglobin, lag time - thrombin generation, prothrombin time and time to peak thrombin levels were significantly lower in those experiencing VTE events compared to patients who did not experience any events (Table 1). D-dimer levels on day-1 after cancer surgery were reported in two studies which, when pooled, revealed that cancer patients with subsequent VTE had higher d-dimer levels post-operatively compared to those with no events (Table 1). Moreover, pre-treatment hemoglobin levels 100 g/L was significantly associated with future VTE risk [OR: 1.42 (95%CI: 1.03-1.97), I 2=0%, n=11] while neutrophil lymphocyte ratio 3 was associated, yet insignificant [OR: 1.60 (95%CI: 0.99-2.60), I 2=43%, n=4]. Pre-treatment platelet count 350 x 10 9/L and white blood count levels 11 x 10 9/L were not significantly associated with future VTE risk [OR: 0.84 (95%CI: 0.66-1.06), I 2=0%, n=9 and 1.32 (0.86-2.03), I 2=56%, n=8, respectively]. From the 51 studies included in the meta-analyses, 27 studies had a low risk of bias, 19 studies had a moderate risk of bias and 5 studies had a high risk of bias. In conclusion, nine blood biomarkers were found to be significantly associated with VTE in cancer patients. Their utility as predictors of VTE in thrombotic risk assessment models may help in optimising VTE prediction and should be further explored in future studies.

Luspatercept in the Treatment of Beta Thalassemia in Italy: Lights and Shadows in Clinical Practice

Luspatercept has been demonstrated to reduce the need for blood transfusion with manageable side effects in clinical trials, thus receiving the approval for the treatment of anemia associated with transfusion dependent beta thalassemia in adults. However, very little data on its safety and efficacy in real life have been hitherto published. Special warnings and precautions for use refer to the possibility of occurrence of thromboembolic events, extramedullary hemopoiesis masses and increased blood pressure. Ten Italian Specialized Centres for the treatment of Hemoglobinopathies, with the patronage of the “Società Italiana Talassemie ed Emoglobinopatie” (SITE), evaluated the effects of luspatercept in terms of safety and blood transfusion reduction in 116 patients (Table 1) who received the first dose of the drug after its marketing. The median duration of treatment was 158 days (min-max: 15-442). β globin genotype was β 0/β 0 in 42 subjects (36.2%), β 0/ β + in 33 (28.4%), β +/ β + in 23 (19.8%), β 0/β wt plus α gene triplication in 4 (3.4%) and unknown in 14 (12%). Sixty-four patients (55.2%) were splenectomized. At the time of data collection, 32 patients (27.6%) had already discontinued the drug. Discontinuation had occurred after a median time of 132 days of treatment (min-max: 15-338) due to insufficient efficacy in the judgement of the physician (10) or patient (3), side effects attributed to luspatercept (16) that were detrimental to the continuation of therapy in the judgement of the physician (6) or patient (10), pregnancy (1) and other causes (2). There were 13 patients with a transfusion-free interval of at least 8 weeks during the treatment period (median 12 weeks, min-max range 9-48). Their median age at baseline was 37.6 years (min-max range 18.4 - 51.6) and age at first transfusion 24 years (min-max range 1 - 33). β globin genotype was β 0/ β 0 in 1 (7.7 %), β 0/ β + in 2 (15.4 %), β +/ β + in 7 (53.8 %), β 0/ β wt plus α gene triplication in 3 (23.1 %). Patients who decreased transfusion requirements by ≥ 33% and ≥ 50% in at least one of the follow-up periods of 12-weeks were 52 (44.8%) and 36 (31%), respectively. When considering the 13-24 week interval (considered as the primary endpoint of the Believe study), of the 66 patients who completed the second follow-up, 31 of 66 patients (47.0%) reduced their transfusion load by ≥33% and 20 of 66 patients (30%) by ≥50%. Focusing on the first two quarters of treatment, the pairwise t test showed a progressive and significant (p&amp;lt;0.05) reduction in the number of transfused units and pure red blood cell volumes (figure). There were no significant differences between the pre-treatment hemoglobin value and that during treatment. Serum ferritin also decreased progressively (p&amp;lt;0.05) during treatment (basal: median 576 ng/mL (Q1-Q3: 289-992); weeks 1-12: 479 ng/mL (232- 848); weeks 13-24: 385 ng/mL (212-644). The pregnancy that was initiated during the luspatercept treatment is still ongoing and no definitive information can be given. Sixty patients (51.7%) reported at least one side effect potentially related to luspatercept. The most frequent side effects were bone pain (40), asthenia-fatigue (11), hypertension requiring therapy or modification of therapy (11), joint pain (11), folic acid deficiency (6), heart palpitations (4) and edema (4). In two patients, an asymptomatic increased volume of masses of extramedullary erythropoiesis was reported. Another two patients presented with thromboembolic events: ischemic stroke in one case and superficial venous thrombosis in the other. Both were splenectomized with no other known risk factors. Despite the limitations of the short duration of follow-up, the analysis reports several significant results. The high percentage of patients who decided not to continue treatment underlines the need for a proper management of patient expectations and selection. The drug proves to be effective also in real life and those who respond best in the short and medium term seem to be who already have residual erythropoiesis, as seen from the age at the start of transfusions and the genotype of those who have had a long period of transfusion independence. Although the drug is generally well-tolerated, some adverse events appear more frequent than reported in Believe. Finally, the report of the two patients who developed a thromboembolic event including stroke, suggests the importance of continuing to be cautious in this regard.

Translating an HPFH-Mechanism into Oral Small Molecule Therapy for Beta-Hemoglobinopathies: Clinical Proof-of-Principle

Introduction: Hereditary persistence of fetal hemoglobin (HPFH) down-modulates co-inherited sickle cell disease (SCD) severity, encouraging characterization of HPFH-mechanisms for interventional reprise. One HPFH mechanism is polymorphisms in DNA methyltransferase 1( DNMT1) that decrease DNMT1 protein stability (Gong et al, Blood 2021), agreeing with biochemical observations that DNMT1 mediates repression of fetal hemoglobin (HbF) genes by BCL11A. Here we describe translation of this HPFH-mechanism into oral therapy for SCD patients at high-risk for early mortality (Steinberg et al, JAMA 2004) despite standard-treatments. Methods and Results: The small molecule decitabine (Dec) contains a pyrimidine ring modification that binds and depletes DNMT1 and a natural deoxyribose that incorporates into DNA without terminating chain synthesis: minimum biologically effective doses of Dec, to deplete DNMT1 without cytotoxicity, can thus be found (reviewed in Zavras et al, Clin Ca Res, 2021). Other key properties of Dec are tropism to hematopoietic precursors, driven by high expression in these cells of deoxycytidine kinase that phosphorylates Dec, and rapid catabolism in vivo by cytidine deaminase (CDA), that severely restricts Dec bioavailability and half-life. We therefore combined Dec with a CDA-inhibitor tetrahydrouridine (THU): dose and schedule of THU/Dec that depleted DNMT1 without cytotoxicity to hematopoietic precursors in vivo were identified in non-human primate studies and Phase 1 clinical trials (Molokie et al, PLoS Med 2017), and here we describe interim results from proof-of-principle study in patients with SCD ( Table 1). Study interventions were oral THU/Dec (~10/0.2 mg/kg) 1X/week with or without oral nicotinamide (vitamin B3) 1 g/day. B3 was studied because it is a direct precursor of NADH, a fundamental antioxidant currency and also a cofactor for epigenetic enzymes that channel hematopoiesis to erythropoiesis vs megakaryopoiesis, to potentially counter an expected side-effect of THU/Dec of increasing platelets. Randomization was to THU/Dec vs B3 for 12 weeks, followed by THU/Dec + B3 for 12 weeks, then option to extend therapy for a further 24 weeks. Standard clinical and laboratory parameters were measured. Six patients enrolled, were randomized equally to THU/Dec or B3, and opted to extend. Dose-limiting toxicities (DLTs), including neutropenia or thrombocytosis, did not occur ( Table 1). In the year preceding study-treatment, 15 vaso-occlusive crises (VOC) requiring hospitalization were documented ( Table 1). By comparison, during 52 weeks on-study (48 weeks on-therapy, 4 weeks follow-up), the grade 3/4 adverse events were VOC hospitalizations x3 (1 during follow-up without therapy, 1 during B3 alone, 1 during B3 + THU/Dec therapy), hyperkalemia x2, and non-cardiac chest pain x1 ( Table 1)(p=0.04, paired t-test 2-sided). THU/Dec dose (7.6/0.15 mg/kg) was below the Phase 1 identified minimum biologically effective dose window (8-12/0.16-0.25 mg/kg, protocol since amended to accommodate high body weights) in one patient (TDN04) who accordingly did not have HbF% or hemoglobin increases ( Fig.1). In the 5 other patients, HbF increases (pre-treatment to maximum) were: 9.4 to 17.3, 5.9 to 11, 3.4 to 9.3, 3.3 to 16.3 and 5.7 to 10 % ( Fig.1). There were corresponding improvements in hemolysis and coagulation pathway parameters (LDH, total bilirubin, D-Dimer), and total hemoglobin increased from 9.9 to 11.5, 8.7 to 10.6, 6.6 to 7.7, 5.7 to 7.1 and 8 to 9.7 g/dL respectively. TDN01 and 06, the two patients with lowest pre-treatment hemoglobin, requested and resumed THU/Dec post-study by Expanded Access. Conclusions: This is the longest-term treatment to date of oral THU/Dec to target DNMT1 in patients with SCD, with or without B3. Subjective and objective improvements were sustained without DLTs in high-risk patients who displayed known negative prediction markers for response to hydroxyurea (HbF% &amp;lt;7.5%, reticulocyte count &amp;lt;300 x10 9/L - Steinberg et al, Blood 1997). The safety and efficacy signals align with scientific target validation data, and together with accessibility, support relevance to SCD patient needs and goals worldwide, bearing in mind major study limitations of single-site enrollment and only 6 patients.

Study the Efficacy of Argon Plasma Coagulation or Endoscopic Band Ligation versus Their Companion in Management of Gastric Antral Vascular Ectasia in Cirrhotic Patients

Abstract Background Gastric antral vascular ectasia (GAVE) is a rare and often misdiagnosed cause of upper gastrointestinal bleeding accounts for up to 4% of all non-variceal upper gastrointestinal bleedings. Multiple options are available for the treatment of GAVE including endoscopic, surgical and medical therapies. Aim of the Work The aim of this study to evaluate the effect of APC followed by EBL in comparison to APC or EBL alone for the treatment of bleeding GAVE in cirrhotic patients. Patients and Methods We conducted this study on 45 adult cirrhotic patients with overt or occult bleeding from GAVE. Patients were divided into 3 groups: 15 patients in each group. Group I was treated with APC alone, group II was treated with EBL alone and Group III was treated with APC followed by EBL. Results In the current study, no statistically significant difference was detected between both groups regarding the etiology of liver cirrhosis, clinical presentation, laboratory or ultrasound findings with special emphasis on pre-treatment hemoglobin value, hospitalizations. APC alone was found to was found to be less effective in the treatment of GAVE when compared to both techniques (EBL and the combined therapy) which were effective in the treatment of GAVE and GAVE recurrence. EBL alone was found to require less number of treatment sessions but required more number of rubber bands and. Combined therapy (APC followed by EBL) successfully decreased the number of banding sessions and decreased the number of rubber bands required to treat GAVE. Conclusion Combined therapy (APC followed by EBL) and EBL alone are effective methods in the treatment of bleeding GAVE in Egyptian cirrhotic patients. EBL alone requires less number of treatment sessions but may require a big number of applied rubber bands. Combined therapy (APC followed by EBL) successfully decreased the number of banding sessions and decreased the number of rubber bands required to treat GAVE. So, in mild cases when less number of rubber bands seems to be required, it is advisable to start with EBL alone: while in severe cases where a large number of rubber bands seems to be required, it is advisable to use combination therapy of APC and EBL.

A predictive survival model for patients with stage IV oropharyngeal squamous cell carcinoma treated with chemoradiation.

To evaluate the pre-treatment and post-treatment clinical factors associated with rate of survival at 1, 3, and 5years in stage IV oropharyngeal cancer patients treated with concurrent chemoradiation with/without neoadjuvant chemotherapy. This retrospective cohort study involved 128 Stage IV oropharyngeal cancer patients that were treated at our tertiary referral center between 2008 and 2020. The pre-treatment and post-treatment clinical parameters including nutritional status and inflammatory markers were retrospectively reviewed. The 5-year overall survival rate for all patients was 36.72%. The disease-specific survival (DSS) at 1-year and 3-year were 80% and 63%, whereas the disease-free survival (DFS) at 1-year and 3-year were 49% and 40%, respectively. In multivariate analyses, pretreatment hemoglobin (Hb) < 12g/dL (hazard ratio [HR] 2.551, 95% confidence interval [CI] 1.366-4.762, p = 0.003), pretreatment systemic immune inflammation (SII) ≥ 1751 (HR 2.173, 95% CI 1.015-4.652, p = 0.046), and posttreatment systemic inflammation response index (SIRI) ≥ 261 (HR 2.074, 95% CI 1.045-4.115, p = 0.037) were independent indicators for worsened DSS. Pretreatment Hb < 12g/dl (HR 1.692, 95% CI 1.019-2.809, p = 0.032), pretreatment SII ≥ 1751 (HR 1.968, 95% CI 1.061-3.650, p = 0.032), and posttreatment SII ≥ 1690 (HR 1.922, 95% CI 1.105-3.345, p = 0.021) were independent indicators for worsened DFS. A nomogram was developed using pretreatment Hb, pretreatment SII, and posttreatment SIRI to forecast DSS. The pretreatment Hb, pretreatment SII, posttreatment SII, and posttreatment SIRI are associated with survival in patients with stage IV oropharyngeal cancers. The developed nomogram aids in survival prediction and treatment adjustment.

Nomogram for prognosis of elderly patients with cervical cancer who receive combined radiotherapy

This retrospective study identified prognostic factors to help guide the clinical treatment of elderly patients (≥ 65 years) with cervical cancer who had undergone radiotherapy. A personalized model to predict 3- and 5-years survival was developed. A review was conducted of 367 elderly women with cervical cancer (staged II–III) who had undergone radiotherapy in our hospital between January 2012 and December 2016. The Cox proportional hazards regression model was used for survival analysis that considered age, hemoglobin, squamous cell carcinoma antigen, pathologic type, stage, pelvic lymph node metastasis status, and others. A nomogram was constructed to predict the survival rates. The median follow-up time was 71 months (4–118 months). The 3- (5-) years overall, progression-free, local recurrence-free, and distant metastasis-free survival rates were, respectively, 91.0% (84.4%), 92.3% (85.9%), 99.18% (99.01%), and 99.18% (97.82%). The following were significant independent prognostic factors for overall survival: tumor size, pre-treatment hemoglobin, chemotherapy, and pelvic lymph node metastasis. The C-index of the line chart was 0.699 (95% CI 0.652–0.746). The areas under the receiver operating characteristic curves for 3- and 5-years survival were 0.751 and 0.724. The nomogram was in good concordance with the actual survival rates. The independent prognostic factors for overall survival in elderly patients with cervical cancer after radiotherapy were: tumor size, pre-treatment hemoglobin, chemotherapy, and pelvic lymph node metastasis. The novel prognostic nomogram based on these factors showed good concordance with the actual survival rates and can be used to guide personalized clinical treatment.

Ameliyat edilebilir Rahim Ağzı Kanserinde Hematolojik İnflamatuar Belirteçler ile Genel Özellikler Arasındaki İlişki; HALP indeksinin yeri.

Background: Cervical cancer is the most common gynecologic malignancy and the leading cause of cancer-related mortality in women worldwide. Systemic inflammatory reactions in cancer patients impact nutrition, function, and prognosis. Poor nutritional health is linked to a worse prognosis in several malignancies. A new score called the hemoglobin-albumin-lymphocyte-platelet (HALP) index was developed using dietary and inflammatory deficiencies.&#x0D; Method: This retrospective study and CC patients diagnosed from January 2012 to December 2020 who were operated for cervical cancer. Pre-treatment hemoglobin (Hb), albumin (Alb), lymphocyte count (Lc), and platelet (Plt) measurements were made for laboratory research.&#x0D; Results: This retrospective study revealed 74 non-metastatic cervical cancer (median age was 55, ranging from 30 to 86 years). According to the FIGO stage, the percentage of stages 1 and 2 were 78% (58 patients), and 22% (16 patients). Neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR), and HALP index were analyzed with LVSI, parametrial invasion, tumor size, histologic type, and duration of hospital stay; we could not find any significant correlation between the analysis. &#x0D; Conclusion: NLR, PLR, and HALP index have no prognostic value in early operable cervical cancer patients regarding the pathologic features. Prospective multicenter and more patient studies will clarify how the hematologic parameters affect oncologic outcomes.

Effect of Baseline Hemoglobin Level on Prognosis in Nasopharyngeal Cancer Patients Receiving Chemoradiotherapy

Objective: To explore retrospectively how pretreatment hemoglobin levels affected the prognosis of patients with nasopharyngeal cancer receiving chemoradiotherapy. Methods: Clinical data of 97 nasopharyngeal cancer patients who received definitive chemoradiotherapy between 2000 and 2022 were analyzed. We accepted the cut-off value of hemoglobin as 11.0g/dL. Results: In general, 13 (13%) of patients were Hb≤11g/dL, while 84 (86%) was Hb&gt;11g/dL. Median survival times were 76 (95%CI 19-132) months and 205 (95%CI 157-252) months for Hb≤11g/dL and Hb&gt;11g/dL patients, respectively. 1, 2, 3 and 5 year survival rates were 67.7%, 67.7%, 67.7% and 58% for Hb≤11g/dL and 90.3%, 83.6.2%, 75.2% and 66.1% for Hb&gt;11g/dL patients, respectively, and this difference show no statistical significance (p=0.254). When we evaluated patients according to WHO criteria for anemia (hemoglobin &lt;12g/dL (female) or &lt;13g/dL (male)), the median survival time was 220 (95%CI 190-255) months for non-anemic patients whereas it was 76 (95%CI 0-157) months for anemic patients. 1, 2, 3 and 5 year survival rates were 92.5%, 87.6%, 78.8% and 68.9% for non-anemic and 75%, 67.5%, 63.7% and 55.8% for anemic patients, respectively. There was statistically significant difference between the two groups (p=0.013). Conclusion: In our study, although Hb&lt;11g/dl before chemoradiotherapy did not show a statistically significant difference in nasopharyngeal cancer patients, the median overall survival of 76 months in Hb≤11g/dL patients and 205 months for Hb&gt;11g/dL patients. However, pretreatment anemia according to WHO criteria, and Hb≤11 g/dL in male patients were found to be independent adverse prognostic factors.

Personalized [177Lu]Lutetium-PSMA Therapy for Patients with Pre-Treated Castration-Resistant Prostate Cancer: A Single Institution Experience from a Comprehensive Cancer Centre.

Castration resistant prostate cancer (CRPC) is characterized by an aggressive biological behavior with a relatively short survival time, especially in progressive tumors pretreated with new hormonal agents and taxane chemotherapy. [177Lu]-Lutetium-PSMA (Lu-PSMA) treatment has proven efficacy in these patients. However, around 30% of the CRPC patients do not benefit from Lu-PSMA treatment, and little is known about predictive factors for treatment success if Lu-PSMA is offered in an individualized approach based on clinical and laboratory features. In this monocentric retrospective study, 86 CRPC patients receiving Lu-PSMA treatment were evaluated. The focus of the study was to describe clinical factors at baseline and during early treatment that are related to overall survival (OS). In addition, PSMA PET/CT-, PSA-response, and safety and tolerability (CTCAE adverse event reporting) were assessed. Efficacy endpoints were calculated using stratified Kaplan-Meier methods and Cox regression models. Mean applied dose was 17.7 GBq (mean 5.3 ± 1.1 GBq per cycle) with an average of 3.6 (range 1-8) therapy cycles. Patients were followed up for a mean of 12.4 months (range 1-39). The median OS was 15 months (95% CI 12.8-17.2). The best overall response rate in patients assessed with PSMA PET/CT and PSA response was 27.9%, and 50.0% had at least stable disease. Nine patients had a ≥grade 3 adverse event with anemia being the most frequent adverse event. Positive predictors for prolonged OS from baseline parameters were pre-treatment hemoglobin level of ≥10 g/dL and a lower PSA values at treatment start, while the presence of visceral or liver metastases were not significantly associated with worse prognoses in this cohort. With careful patient selection, an individualized Lu-PSMA treatment approach is feasible and patients with dose-limiting factors or visceral metastases should be included in prospective trials.