Anemia Grade Research Articles

Initial Experience with [177Lu]Lu-PSMA-617 After Regulatory Approval for Metastatic Castration-Resistant Prostate Cancer: Efficacy, Safety, and Outcome Prediction.

[177Lu]Lu-PSMA-617 was approved by the U.S. Food and Drug Administration for patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC). Since the time of regulatory approval, however, real-world data have been lacking. This study investigated the efficacy, safety, and outcome predictors of [177Lu]Lu-PSMA-617 at a major U.S. academic center. Methods: Patients with mCRPC who received [177Lu]Lu-PSMA-617 at the Johns Hopkins Hospital outside clinical trials were screened for inclusion. Patients who underwent [177Lu]Lu-PSMA-617 and had available outcome data were included in this study. Outcome data included prostate-specific antigen (PSA) response (≥50% decline), PSA progression-free survival (PFS), and overall survival (OS). Toxicity data were evaluated according to the Common Terminology Criteria for Adverse Events version 5.03. The study tested the association of baseline circulating tumor DNA mutational status in homologous recombination repair, PI3K alteration pathway, and aggressive-variant prostate cancer-associated genes with treatment outcome. Baseline PSMA PET/CT images were analyzed using SelectPSMA, an artificial intelligence algorithm, to predict treatment outcome. Associations with the observed treatment outcome were evaluated. Results: All 76 patients with PSMA-positive mCRPC who received [177Lu]Lu-PSMA-617 met the inclusion criteria. A PSA response was achieved in 30 of 74 (41%) patients. The median PSA PFS was 4.1 mo (95% CI, 2.0-6.2 mo), and the median OS was 13.7 mo (95% CI, 11.3-16.1 mo). Anemia of grade 3 or greater, thrombocytopenia, and neutropenia were observed in 9 (12%), 3 (4%), and 1 (1%), respectively, of 76 patients. Transient xerostomia was observed in 23 (28%) patients. The presence of aggressive-variant prostate cancer-associated genes was associated with a shorter PSA PFS (median, 1.3 vs. 6.3 mo; P = 0.040). No other associations were observed between circulating tumor DNA mutational status and treatment outcomes. Eighteen of 71 (25%) patients classified by SelectPSMA as nonresponders had significantly lower rates of PSA response than patients classified as likely responders (6% vs. 51%; P < 0.001), a shorter PSA PFS (median, 1.3 vs. 6.3 mo; P < 0.001), and a shorter OS (median, 6.3 vs. 14.5 mo; P = 0.046). Conclusion: [177Lu]Lu-PSMA-617 offered in a real-world setting after regulatory approval in the United States demonstrated antitumor activity and a favorable toxicity profile. Artificial-intelligence-based analysis of baseline PSMA PET/CT images may improve patient selection. Validation of these findings on larger cohorts is warranted.

Bone marrow toxicity in patients with locally advanced cervical cancer undergoing multimodal treatment with VMAT/IMRT: are there dosimetric predictors for toxicity?

PurposeFor women with locoregionally advanced cervical cancer, the standard of care treatment is the curatively intended chemoradiation therapy (CRT). A relationship between bone marrow (BM) dose–volume histograms (DVHs) and acute hematological toxicity (HT) has been debated recently. Aim of this study was the evaluation of BM dose constraints and HT in a contemporary patient cohort.MethodsRadiation treatment plans of 31 patients with cervical cancer (FIGO stage IIB–IVB) treated with intensity-modulated radiotherapy and simultaneous chemotherapy were explored retrospective. Pelvic bones (PB) and femoral heads (FH) were contoured and DVHs were correlated with white blood cells (WBC), hemoglobin levels and platelets.ResultsComparing the absolute blood levels with the dose volumes of both FH and PB the data showed a significant correlation between WBC and the median dose of the FH and the median dose, V30Gy, V40Gy and V50Gy of the PB. A correlation between the toxicity grade of anemia and mean dose, maximum dose and V5Gy of the PB was found. Counting the highest grade of HT of all three blood levels of each patient, significant correlations were found for the mean and median dose, V30Gy, V40Gy and V50Gy of the PB.ConclusionThe results show that blood levels may correlate with distinct dosimetric subvolumes of critical bone marrow compartments with a potential impact on therapeutic outcome and treatment-related toxicity. The data presented are in line with the previous findings on the relevance of dosimetric exposure of pelvic bony subvolumes.

Study on incidence and clinical profile of anemia in children aged 1 years to 15 years attending tertiary care hospital

Background: Children are considered as an important asset for any country and their health as one of the important indicators of a healthy country. There are various factors influencing children's health, with anemia being one of them. Anemia is a major global health problem, especially in developing countries like India, despite the fact that this problem is largely preventable and easily treatable. Methods: It is a descriptive study conducted in 140 children aged 1 year to 15 years who presented with anemia in the department of pediatrics at Navodaya Medical College Hospital and Research Center, Raichur. Aim was to study the incidence and profile of anemia in children aged 1 years to 15 years. Results: A total 0f 140 cases aged between 1- 15 years were included in the study. The highest number of cases occurred in the 11-15 years age group (38.5%), followed by the 6-10 years group (35.0%). There is more female preponderance in this study (55.7%) compared to males (44.2%). Moderate degree of anemia was the commonest grade of anemia (42.8%) The most common cause of anemia in this study was iron deficiency, accounting for 58 cases (41.4%) followed by 17 cases (12.1%) had megaloblastic anemia. Conclusions: Iron deficiency anemia is a preventable cause of cognitive impairment, and early interventions can prevent the morbidity and mortality associated with anemia. Despite the implementation of national programs to combat iron deficiency, the problem persists. Early detection of anemia among these children enables the planning of suitable interventions, such as nutritional education for mothers, growth monitoring, nutritional supplementation, deworming, and more, to effectively address and mitigate the issue.

Patterns of Geriatric Anemia – A Clinicopathological Study

Background : Anemia is a common condition in elderly especially in hospitalized geriatric patients and is known to be associated with increased morbidity and mortality. The UN agreed cut off to refer to the older population is 60years and above. Anemia in the elderly is defined as a haemoglobin concentration below12 gm/dl in women and below 13gm/dl in men. Objectives: To study the grade and patterns of anemia in Geriatric age group of both sex with clinicopathological correlation. Materials and Methods: It is a Prospective study of 2 years from May 2018 to April 2020 carried out in KIMS, Hubbali. A statistically significant sample size was 400. Results: Among the total geriatric cases of 400, males were 233 (58.25%) and females were 167 (41.75%). In which majority of them were in the age group between 60-69 years that is 237 (59.25%) cases, followed by 121 (30.25%) cases, 38 (9.5%) cases and 4 (1%) cases were in the age group between 70-79 years, 80-89 and above 90 years respectively. The study showed that majority of the cases belonged to the Grade 1 anemia (69.25%). On smear examination most common morphological pattern was Normocytic Normochromic Anemia (75%), followed by Microcytic Hypochromic Anemia (18%). On clinical history correlation, majority of them were asymptomatic 52% and 38% of cases presented with fatigue. Conclusion: The study concludes that diagnosing different morphological patterns of geriatric anemia and its clinical correlation helps in reducing the morbidity and mortality of geriatrics related to anemia and also facilitate the clinicians to improve the treatment protocols and prophylactic therapy. Keywords Geriatrics, Patterns, Anemia

Bioanalytical method validation for therapeutic drug monitoring of olaparib in patients with ovarian cancer

Olaparib, an oral poly-ADP ribose polymerase (PARP) inhibitor, is a relatively new anticancer drug. It is essential to find TDM-guided dosage for better safety and tolerability of patients. However, first, it is important to develop a suitable analytical method to conduct reliable TDM. The aim of the study was the validation of UPLC-MS/MS method for TDM of olaparib in patients with ovarian cancer, with a particular attention to optimization of recovery. The validation of the method under analysis were accomplished by the ICH guidelines. The recovery of olaparib was optimized with the Central Composite Design (CCD). The TDM study was conducted on 10 patients with ovarian cancer treated with olaparib. The method validation was characterized by good precision (CV &lt;9.09%), accuracy (89.23-111.08%) and linearity (r=0.9993) within the range of 100-20,000 ng/mL, with limits of detection of 30 ng/mL. The ten-minute shaking time combined with 100% acetonitrile resulted in an estimated value of 98% for recovery and the observed value of 98%. The olaparib concentrations in the patients’ plasma were 1078.2-16773.8 ng/mL. A wide range of olaparib concentrations was observed in the patients reported adverse reactions included: anemia (grade 1, n=2), neutropenia (grade 1, n=1), and hyperkeratinemia (grade 1, n=1). The method validation included all required procedures showing that the measurement of olaparib concentrations in the plasma was reliable for the intended application, such as TDM.

Feasibility and tolerability of eribulin-based chemotherapy versus other chemotherapy regimens for patients with metastatic triple-negative breast cancer: A single-centre retrospective study.

e13135 Background: Patients with Triple-negative breast cancer (TNBC) face a poor prognosis and limited therapeutic options. Current data on eribulin usage to treat TNBC is scarce. Therefore, we sought to compare the feasibility and tolerability of eribulin-based regimens with other chemotherapy regimens in patients with TNBC. Methods: This retrospective study was conducted at Fujian Medical University Cancer Hospital and included 159 patients with TNBC enrolled between October 2011 and January 2023. Patients underwent treatment with eribulin-based and other chemotherapy regimens. The study's primary endpoints were progression-free survival (PFS) and overall survival (OS), while its secondary endpoint was objective response rate (ORR), disease control rate (DCR), and safety. Tumour response was assessed using RECIST V.1.1 criteria. Results: Of the 159 participants in the study, 42 individuals (26.4%) received treatment with eribulin, whereas 117 participants (73.6%) were administered alternative chemotherapy regimens, which included nab-paclitaxel-based therapy (n=45) and platinum-based therapy (n=51). The follow-up period for all patients ended on December 31st, 2022, and the median follow-up time was 18.3 months (range:0.7-27.5). Following propensity score matching (PSM), eribulin-based treatment resulted in longer median PFS compared to platinum-based (hazard ratio (HR)=0.41, p=0.006), nab-paclitaxel-based (HR=0.36, p=0.001) and other chemotherapy (HR=0.39, p&lt;0.001). Also, eribulin induced a remarkable prolongation of the median OS duration in all three comparative groups. The group receiving eribulin treatment showed significantly reduced incidences of any grade of anaemia, peripheral neuropathy, nausea and vomiting, and hair loss compared to other chemotherapy groups. Conclusions: For the salvage treatment of advanced TNBC, treatment with eribulin produced longer median PFS and OS than other chemotherapy regimens, with a well-tolerated safety profile. Therefore, further investigation of eribulin-based treatment in larger randomized trials for patients with advanced TNBC is warranted. Clinical trial information: NCT05953909 .

Clinical Implications of Anemia Among Eastern Sudanese HIV Survivors.

Background In HIV patients, anemia is the most common hematopoietic consequence, and it has a major influence on life satisfaction, morbidity, and survival. The epidemiology of anemia in this cohort in Sudan, however, is poorly characterized. Aim This study aims to assess the prevalence of anemia and its implications among HIV-positive patients. Methods An observational case-control study was administered in 44 clinical HIV-positive cases at the Sudan National AIDS Program (SNAP), Red Sea State, Sudan, between January 2018 and December 2019. A total of 44 HIV-negative subjects as controls were enrolled. HIV-infected patients' demographic and clinical data, involving anemia and its outcome, were examined. WHO threshold was used to rank the clinical course of anemia in these patients. Results Of the 44 HIV patients examined, the mean age was 33.0 ± 11.2 years. Thirty (68.1%) were males, and 14 (29.8%) were females. The overall prevalence of anemia was 63.6% (95% CI 57.8-69.94%): mild grades of anemia at 25% (95% CI 14.4-34.4%), moderate grades of anemia at 36.4% (95% CI 28.7-43.2%), and severe anemia at 2.3% (95% CI 1.3-3.3%). In this study, 18 (64.3%) anemic patients showed normocytic thin smear pictures, among whom 44.3% were males and 20.5% were females. Microcytic anemia was seen in 17.8% of patients, while autoimmune hemolytic anemia was also detected in 17.8% of patients. The prevalence of anemia increased significantly with decreasing total lymphocyte count (TLC): 6.8% and 13.6% among patients with TLCs <1,000 and 1,000-4,800 cells/mm3, respectively (P = 0.016). Male sex was significantly associated with increased odds of anemia (OR 1.90, P = 0.049). Conclusion Anemia is a public comorbidity among HIV patients in the east of Sudan. Normocytosis is the most prominent form of anemia related to hypoproliferation in eastern Sudan, an event that can be triggered either by HIV chronicity or its combination with nutritional inadequacies. To prevent anemia progression and promote quality lifestyles, timely screening and appropriate therapy for anemia are critical, particularly for those with a low TLC.

Validation of new invasive digital hemoglobinometer for hemoglobin estimation as point-of-care device among pregnant women in a facility setting India

Background: Anemia poses a significant health challenge for pregnant women (PW), and accurate and timely diagnosis is essential for effective management. Objective: The objective was to assess the diagnostic validity of the new digital hemoglobinometer for hemoglobin against laboratory-based hematology autoanalyzer among PW. Methodology: The study was conducted at a secondary-level healthcare facility among 204 pregnant women to be sampled conveniently, their sociodemographic and iron intake data collected, and hemoglobin levels assessed using a digital hemoglobinometer (Device A) and a hematology analyzer. Specificity, sensitivity, PPV, NPV, diagnostic accuracy, and method agreement were evaluated via Bland-Altman analysis and Lin's concordance correlation coefficient. Results: The proportion of anemia using the Device A was 64.7% while the hematology analyzer reported a proportion of 52.9%. Device A showed a sensitivity of 97.22%, specificity of 80.30%, and diagnostic accuracy of 86.3%, with substantial agreement indicated by Cohen's kappa coefficient (kappa = 0.72) and the weighted kappa coefficient for different grades of anemia was 0.67. Bland-Altman analysis revealed a mean difference (bias) of -0.28 (± 0.5) between the two methods, with limits of agreement at -1.24 and 0.68. Lin's concordance correlation coefficient of absolute agreement was 0.91. Conclusion: The DH showed high sensitivity and diagnostic accuracy for anemia detection in PW, with substantial agreement with the hematology analyzer. It offers a convenient and rapid alternative for POC hemoglobin estimation in resource-constrained settings.

Abstract CT063: Phase Ib trial of ATR inhibitor (ATRi) tuvusertib + ATM inhibitor (ATMi) lartesertib (M4076) in patients (pts) with advanced solid tumors

Abstract Ataxia telangiectasia-mutated (ATM) and Rad3-related (ATR) protein kinases are critical in the DNA damage response. ATR and ATM genes have a synthetic lethal relationship in cancer and ATMi synergistically potentiates the efficacy of ATRi in vitro and in vivo. Here, we studied the combination potential of the highly potent, oral agents tuvusertib and lartesertib. The open-label, multicenter study DDRiver Solid Tumors 320 (NCT05396833) investigated safety, tolerability, PK and PD of tuvusertib + lartesertib in pts with advanced solid tumors refractory to standard therapy. PK samples were analyzed by a validated LC/MS method, and PD via γ-H2AX in ex vivo-stimulated CD45+ fraction by flow cytometry. As of 03.01.2024, 42 pts received ascending doses of tuvusertib + lartesertib. 5 pts experienced DLTs (Table 1). Frequent TEAEs (≥25 % of pts, any grade) were: anemia 62 %, nausea 45 %, fatigue and vomiting (43 % each). Grade ≥3 TEAEs occurred in 21 (50 %) pts; those in ≥3 pts were: anemia (n=9), decreased platelets (n=5), fatigue and decreased neutrophils (n=3 each). Preliminary steady-state PK showed rapid absorption: median Tmax of ~2-3 h (tuvusertib) and ~1-3.5 h (lartesertib); mean elimination half-life range of ~3.2-4.5 h (tuvusertib) and ~5.5-8.7 h (lartesertib); minimal accumulation. Exposure of the combination was consistent with respective monotherapies, indicating no clinically meaningful mutual drug-drug interactions. Preliminary PD showed complete or almost complete target inhibition 1-6 h after tuvusertib ≥130 mg and rebound above baseline after 24 h and target inhibition ~50 % across all time points at lartesertib ≥100 mg. 6 pts (2 ovarian, 2 uterine, 1 prostate cancer and 1 melanoma) had stable disease &amp;gt;16 weeks; 3 remain on treatment. Multiple tolerated combination doses were identified. Tuvusertib 180 mg QD + lartesertib 150 mg QD 2 w on/2 w off was selected for investigation in expansion cohorts in pts with prostate and endometrial cancer. Table 1. DLTs by ascending dose (DLT-evaluable patients) Dose (tuvusertib + lartesertib), mg N DLT DLT AE terms by cohort 2 w on/2 w off regimen 90 + 50 QD 3 No NA 130 + 50 QD 4 No NA 130 + 100 QD 3 No NA 180 + 100 QD 3 No NA 180 + 200 QD 4 Yes, in 2 pts One pt experienced febrile neutropenia Grade 3, neutrophil count decreased Grade 4, anemia Grade 3, platelet count decreased Grade 4, and candida infection Grade 2. The second pt had neutrophil count decreased Grade 4 180 + 150 QD 9 No NA 2 w on/1 w off regimen 180 + 150 QD 4 Yes, in 2 pts Both pts had platelet count decreased Grade 2 and Grade 3 180 + 100 QD 7 Yes, in 1 pt Neutrophil count decreased Grade 4 AE, adverse event; DLT, dose-limiting toxicities; N, DLT-evaluable patients; NA, not applicable; PD, pharmacodynamics; PCa, prostate cancer; PK, pharmacokinetics; pts, patients; QD, once daily, TEAE, treatment-emergent adverse event; w, week Citation Format: Lillian L. Siu, Elena Garralda Cabanas, Valentina Boni, Anthony W. Tolcher, Enrique Sanz Garcia, Jesús Fuentes-Antrás, Omar Saavedra, Deepthi S. Vagge, Giuseppe Locatelli, Burak Kürsad Günhan, Gregory Pennock, Jatinder Kaur Mukker, Ioannis Gounaris, Timothy A. Yap. Phase Ib trial of ATR inhibitor (ATRi) tuvusertib + ATM inhibitor (ATMi) lartesertib (M4076) in patients (pts) with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT063.

Abstract CT224: Preliminary efficacy and safety results from the (TATCIST) trial: A PSMA-directed targeted alpha therapy with FPI-2265 (225Ac-PSMA-I&amp;T) for the treatment of metastatic castration-resistant prostate cancer (mCRPC)

Abstract INTRODUCTION: Targeted α therapy (TAT) in mCRPC is a rapidly advancing class of radiotherapeutics that can effectively deliver potent and local radiation selectively to cancer cells while sparing the surrounding normal cells. Retrospective studies of 225Ac PSMA-RLT (radioligand therapy), have shown promise in pts with mCRPC, where activity correlates with disease characteristics and prior therapies. FPI-2265 (225Ac-PSMA-I&amp;T) consists of a small-molecule PSMA-targeting ligand coupled with a 225Ac radionuclide. Here we present the initial results from TATCIST, an ongoing, open-label, single-arm study (NCT05219500) to evaluate the efficacy and safety of FPI-2265 in pts with mCRPC that was initiated as an investigator-sponsored study then converted into an industry-sponsored trial with more stringent eligibility criteria. METHODS: Eligible pts are required to have progressive mCRPC with PSMA-positive PET. Prior radioligand therapy is permitted. Pts with skeletal metastases presenting as a superscan were excluded upon protocol amendment and excluded from this analysis. Four doses of FPI-2265 at 100 kBq/kg (±10%) are administered at 8-week intervals; de-escalation in cycle 2 and beyond is allowed. Proportion of pts with PSA ≤50%, maximum %PSA decrease, and safety and tolerability of FPI-2265 were assessed. RESULTS: At the time of the data cut (30Jan2024) 30 pts have received ≥1 dose FPI-2265, with 25 pts having ≥12 weeks follow up. For this analysis, 21 pts were evaluable for safety and 20 pts were evaluable for PSA response: 4 pts with superscan were excluded and 1 pt was excluded due to uninterpretable PSA data. In general, pts were heavily pretreated in terms of prior lines of therapy. Most pts (17/21 [81%]) had received a prior taxane, including 8 pts who received ≥2 lines of taxanes. Eight pts received prior 177Lu PSMA-RLT (Lu). PSA50 was achieved in 10/20 pts (50%); In a subset of pts with the baseline PSMA SUVmean &amp;gt;6 (n=13 overall; post-Lu, n=6), PSA50 was achieved in 9 pts (69%). Treatment-related adverse events (TRAEs) included dry mouth (18/21 [86%]), fatigue (10/21 [48%]) dry eye (6/21 [28%]), and anemia (6/21 [28%]). All were Grade 1-2 in severity, expect anemia Grade 3 which was observed in (5/21 [24%]). Other Grade 3 TRAEs included decreased platelet count (3/21 [14%]). No Grade 4 or 5 TRAEs were reported. Dry mouth was primarily Grade 1 (13/21 [62%]) with only 5 patients (24%) experiencing Grade 2 dry mouth; there were no related discontinuations. CONCLUSION: Preliminary efficacy and safety data as of 30Jan24 suggest that FPI-2265 is active in heavily pretreated pts with progressive mCRPC, including pts who received prior Lu therapy. Higher PSMA SUVmean was associated with improved PSA responses, Safety and tolerability were consistent with other published studies of 225Ac-PSMA-RLTs. These initial results support further investigation of FPI-2265 and a new phase 2/3 trial will begin enrolling soon. Citation Format: Ebrahim S. Delpassand, Mohammad Jawed Hashmi, Julia Kazakin, Omer Nawaz, Gabriella Garufi, Joanne Schindler, Luke Nordquist. Preliminary efficacy and safety results from the (TATCIST) trial: A PSMA-directed targeted alpha therapy with FPI-2265 (225Ac-PSMA-I&amp;T) for the treatment of metastatic castration-resistant prostate cancer (mCRPC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT224.

Compliance With NCCN Guidelines for Evaluation and Treatment of Anemia Among Patients With Solid Tumors.

NCCN Guidelines for Hematopoietic Growth Factors recommend evaluation and treatment of anemia in patients with cancer. However, a paucity of data exists regarding compliance with these recommendations. A retrospective cohort study was performed of patients diagnosed with any solid tumor at Vanderbilt University Medical Center from 2008 to 2017. Tumor registry-confirmed cancer cases were identified by ICD-O codes using the Synthetic Derivative database. Anemia was defined as hemoglobin (Hgb) level ≤11 g/dL and graded according to CTCAE version 5.0. Absolute, functional, and possible functional iron deficiency were defined based on NCCN Guidelines. A total of 25,018 patients met inclusion criteria. Median age was 60 years. The most common malignancies were respiratory tract, prostate, and nonprostate urologic (11% each). Among 8,695 patients with Hgb levels available prior to diagnosis, 1,484 (17%) were noted to be anemic proximal to diagnosis. Of the 25,018 patients, 11,019 (44%) were anemic within 6 months of diagnosis. Of these patients, 4,686 (43%) had grade 2 (moderate) anemia and 9,623 (87%) had normocytic anemia. Patients with retroperitoneal/peritoneal cancers had the highest prevalence of anemia (83/110; 75%). A total of 4,125 (37%) underwent any evaluation of their anemia, of whom 1,742 (16%) had iron studies performed and 1,528 (14%) had vitamin B12 or folate studies performed. Fewer than half of patients with anemia received treatment (n=4,318; 39%), including blood transfusion (n=3,528; 32%), oral iron supplementation (n=1,279; 12%), or intravenous iron supplementation (n=97; 1%). Anemia treatment was significantly more frequent as the grade of anemia increased (any treatment among grade 1/mild: 12%; grade 2/moderate: 31%; grade 3/severe: 77%; χ2 [2, n=11,019]=3,020.6; P<.001). Patients with penile and testicular cancers had the highest prevalence of anemia evaluation (n=57; 79%). Anemia is common in patients with solid tumors; yet, compliance with NCCN Guidelines for evaluation and treatment of anemia remains low. There are opportunities to improve compliance with guidelines across the spectrum of cancer care.

Feasibility and tolerability of eribulin-based chemotherapy versus other chemotherapy regimens for patients with metastatic triple-negative breast cancer: a single-centre retrospective study.

Background: Patients with Triple-negative breast cancer (TNBC) face a poor prognosis and limited therapeutic options. Current data on eribulin usage to treat TNBC is scarce. Therefore, we sought to compare the feasibility and tolerability of eribulin-based regimens with other chemotherapy regimens in patients with TNBC. Method: This retrospective study was conducted at Fujian Medical University Cancer Hospital and included 159 patients with TNBC enrolled between October 2011 and January 2023. Patients underwent treatment with eribulin-based and other chemotherapy regimens. The study's primary endpoints were progression-free survival (PFS) and overall survival (OS), while its secondary endpoint was objective response rate (ORR), disease control rate (DCR), and safety. Tumour response was assessed using RECIST V.1.1 criteria. Results: Of the 159 participants in the study, 42 individuals (26.4%) received treatment with eribulin, whereas 117 participants (73.6%) were administered alternative chemotherapy regimens, which included nab-paclitaxel-based therapy (n = 45) and platinum-based therapy (n = 51). The follow-up period for all patients ended on 31 December 2022, and the median follow-up time was 18.3 months (range:0.7-27.5). Following propensity score matching (PSM), eribulin-based treatment resulted in longer median progression-free survival compared to platinum-based (hazard ratio (HR) = 0.41, p = 0.006), nab-paclitaxel-based (hazard ratio = 0.36, p = 0.001) and other chemotherapy (HR = 0.39, p < 0.001). Also, eribulin induced a remarkable prolongation of the median overall survival duration in all three comparative groups. The group receiving eribulin treatment showed significantly reduced incidences of any grade of anaemia, peripheral neuropathy, nausea and vomiting, and hair loss compared to other chemotherapy groups. Conclusion: For the salvage treatment of advanced TNBC, treatment with eribulin produced longer median PFS and OS than other chemotherapy regimens, with a well-tolerated safety profile. Therefore, further investigation of eribulin-based treatment in larger randomized trials for patients with advanced TNBC is warranted.

Chronic renal insufficiency can cause early anemia: A cross-sectional study

Background: Chronic renal insufficiency has emerged as a global health issue, causing significant morbidity and mortality. Anybody can develop anemia but it is very common in people with chronic kidney disease (CKD). Renal anemia develops as a result of CKD, and its prevalence rises as the disease progresses. The WHO defines anemia as a hemoglobin level &lt;13 gm/dl for males as well as women in the post-menopausal age group and ˂12 gm/dl for women in the pre-menopausal age group. Aim and Objectives: This study was done to assess whether a correlation exists between the grades of anemia and various stages of chronic renal insufficiency. Materials and Methods: The authors conducted a cross-sectional study involving 145 subjects with diabetes mellitus and CKD. The primary aim was to investigate the various grades of anemia in different stages of CKD patients. We classified the CKD patients into 5 stages based on GFR rates, as defined by guidelines of the national kidney foundation. Results: This study shows that out of 145 subjects having diabetic nephropathy with CKD, 59 subjects had mild anemia, 60 subjects had moderate anemia, and 26 subjects had severe anemia. Data were analyzed using the SPSS 16.0 version. The qualitative results were presented in frequency, percentages, and graphs. Baseline characteristic cases were compared with grades of anemia. For the correlation between two variables, Pearson and Spearman correlation coefficients were applied. The majority of patients with Grade 2 and Grade 3 CKD had mildto-moderate grades of anemia which worsened as the stage of CKD progressed and came out to be highly significant. Conclusion: This study concludes that anemia is a consistent finding in patients of CKD; the severity of anemia progresses as the kidney function is compromised.

TO ASSESS THE ACCURACY AND RELIABILITY OF PALLOR IN THE ORAL CAVITY AND PALPEBRAL CONJUNCTIVA TO CLINICALLY DIAGNOSE ANAEMIA IN MIDDLE AGED FEMALE PATIENTS BY USING HAEMOGLOBIN AS THE REFERENCE STANDARD

Aim: To accurately determine the reliability of pallor on the dorsal surface of tongue and/or palpebral conjunctiva to diagnose anaemia in middle aged female patients, by using haemoglobin as the reference standard. To correlate pallor with different grades of anaemia according to WHO criteria. Objective: A cost effective chair side clinical observation of pallor to diagnose anaemia in middle aged female patients and to provide counselling thereby reducing the prevalence of anaemia and its associated morbidities, especially in poor resource setting. Method: Between 1st June 2022 to 30th Aug 2022, all female dental outpatients between 40-65 years of age were prospectively examined. Among these subjects,100 female patients with pallor on the dorsal surface of tongue and/or palpebral conjunctiva who met the specified inclusion and exclusion criteria, provided informed consent, and who had undergone blood test within one day of clinical pallor detection were enrolled in the study. Based on haemoglobin levels, anaemia was divided into mild, moderate, and severe according to WHO criterion (Hb: &lt;12g/dl). Anaemia was divided into mild (Hb: 11-11.99 g/dl), moderate (Hb: 7-10.99 g/dl), and severe (Hb: &lt; 7g/dl). Data was expressed as frequency and percentages. Result: In the present study, 82% of subjects with either conjunctival pallor or tongue pallor or both were anaemic with laboratory proven haemoglobin levels &lt; 12 g/dl which was found to be statistically significant. 14.6% subjects were diagnosed with mild anaemia, 51.2% with moderate anaemia, and 34.1% with severe anaemia. Among patients with mild and moderate anaemia, conjunctival pallor out performed tongue pallor whereas in subjects with severe anaemia, tongue pallor outperformed conjunctival pallor. Detecting pallor in a female patient is a dependable sign of anaemia. Furthermore, identifying tongue surface pallor is a strong signal of severe anaemia in female patients whereas conjunctival pallor is a good indicator for mild and moderate anaemia. The effective implementation of dietary counselling has the potential to significantly reduce the prevalence of anaemia.

Clinical characteristics and outcomes of anemic patients with coronary artery disease after percutaneous coronary intervention (systematic review)

Objective: to explore clinical characteristics and the influence of anemic syndrome on long-term outcomes of patients with coronary artery disease underwent percutaneous coronary intervention (PCI). Review writing methodology. A systematic review was performed according to PRISMA methodology using PubMed, Google Scholar, eLibrary, CyberLeninka databases. Search depth —from 2000 to 2022. The review included 16 original studies. Conclusion. It was shown that the patients with PCI and anemia were older, predominantly male sex as compared with patients without anemic syndrome. The risk of adverse short- and long-term outcomes (myocardial infarction, stroke, major bleeding, cardiovascular and non-cardiovascular death) was significantly increased in anemic patients even with a slight decrease in hemoglobin according to WHO criteria (less than 130 g/lfor men and less than 120 g/l for women). But majority of patients were not fit with the criteria of light grade of anemia according federal clinical guidelines (hemoglobin 90-110 g/l). The influence of anemia on outcomes becomes the most significant 12 months after PCI.

The Pattern and Significance of Delivery Outcome in Anaemia-Induced Changes of the Placenta

Abstract Background: Anemia is a clinical sign of the most prevalent nutritional deficiency in pregnant women worldwide. Histopathological study of the placenta provides valuable information on changes due to anemia in pregnancy. Aim: The present study was undertaken to evaluate the significance of macroscopic and histopathological changes in the placenta due to deficiency anemia in pregnancy consequently affecting the delivery outcome. Material and methods: An observational, prospective, cross-sectional study was conducted for one year. All the obstetric patients having hemoglobin (Hb) less than 11gm/dl were included in the study. After applying the exclusion criteria, 57 cases were included in the study. After delivery, the placenta was collected, fixed in formalin, weight measured, dimensions noted and volume was calculated. Gross features were noted and representative tissue was taken for histopathological study. Results: Term pregnancy was found commonly in mild anaemia (17 cases, 30%), preterm delivery in moderate anemia (14 cases, 25%), and Intrauterine fetal death (IUFD) /abortion in severe anemia (2 cases, 3%). The frequency of the presence of increased placental weight, decreased vascularity, increased fibrosis, and endarteritis are obliterans was found significantly higher in higher grades of anemia than in mild anemia. The same gross and histopathological features were significantly associated with poor obstetric outcomes (IUFD/abortion, preterm delivery) than good obstetric outcomes (term pregnancy). Conclusion: Studies of the placenta have a significant role in understanding the pathophysiology of anemia in pregnancy.

Efficacy and Safety of Ino Combined with Reduce Dose R-GDP Regimen in Patients with Relapsed/Refractory B-Cell NHL in China

Background: The combination of immunochemotherapy resulted in satisfactory efficacy and survival for B-cell Non-Hodgkin Lymphoma (NHL). But many patients face no response to combination therapy or the disease progression again. This study aimed to investigate the efficacy and safety of Inotuzumab Ozogamicin (InO) combined with reduce dose R-GDP as a salvage therapy in patients with relapsed/refractory (R/R) B-NLH. Patients and methods: Seven patients with R/R B-NLH or even failure of anti-CD19 and CD22 chimeric antigen receptor (CAR) T cell therapy received InO combined with reduce dose R-GDP combination therapy. All patients received Rituximab (R) 375mg/m 2 intravenously (IV) on day -1, and InO 0.8 mg/m 2 (IV) on day 0. Then Gemcitabine (G) 500-1000mg/m 2(IV), Dexamethasone (D) 40 mg/day (IV) on day 1-4 and Cisplatin (P) 40-75mg/m 2 (IV) on day 1 of each 21-day cycle (±2 days). Treatment was continued for up to two cycles unless progressive disease (PD) or intolerable toxicity occurred. The primary endpoint of this study was the Complete remission (CR) and Overall response rate (ORR). The secondary endpoint of this study was Progression-free survival (PFS), Overall survival (OS) and Adverse events (AE), particularly hematological toxicity. In our study, the response evaluation was detected using computed tomography (CT) or PET-CT. Results: Seven patients with R/R B-NLH received 1-2 cycles of InO combined with reduce dose R-GDP therapy. Three patients did not respond to anti-CD19 and CD22 CAR-T cell therapy or their disease progressed again. The other four patients did not respond to more than 3 lines of combined immunochemotherapy and never achieved Partial response (PR) or CR. Four patients with R/R B-NLH who received 1-2cycles of InO combined with reduce dose R-GDP therapy achieved CR and survived to this day. Three of the four patients had previously received anti-CD19 and CD22 CAR-T cell therapy. Two patients with R/R B-NLH achieved PR after one cycle of InO combined with reduce dose R-GDP therapy, the other one patient achieved Stable disease (SD) only. One R/R B-NLH patient who achieved CR after one cycle of this salvage therapy had a PFS of one year to date without any other treatments. The other three R/R B-NLH patients who achieved CR after 1-2 cycles of this salvage therapy had a PFS of 3-6 months without any other treatments. The other two patients who achieved PR after 1 cycle of this salvage therapy survived 7 months and 2 months, while the only one patient who achieved SD survived one month without any other treatment. The main AE of this study was hematological toxicity. Three patients were defined as 3-4 grade of neutropenia, four patients were defined as 3-4 grade of anemia and three patients were defined as 3-4 grade of thrombocytopenia in this study. Except for one patient who was defined as grade 3 of thrombocytopenia recovered nine months after this salvage therapy, all other patients recovered two to three months after this study. There have been no deaths from severe infections due to hematological toxicity. Conclusions Ino combined with reduce dose R-GDP therapy in patients with R/R B-NLH could be an effective and safety therapy. However, the GDP regimen needs to be reduced appropriately to avoid severe hematological toxicity.

Proton and photon radiotherapy in stage III NSCLC: Effects on hematological toxicity and adjuvant immune therapy

Background and purposeConcurrent chemo-radiotherapy (CCRT) followed by adjuvant durvalumab is standard-of-care for fit patients with unresectable stage III NSCLC. Intensity modulated proton therapy (IMPT) results in different doses to organs than intensity modulated photon therapy (IMRT). We investigated whether IMPT compared to IMRT reduce hematological toxicity and whether it affects durvalumab treatment. Materials and methodsProspectively collected series of consecutive patients with stage III NSCLC receiving CCRT between 06.16 and 12.22 (staged with FDG-PET-CT and brain imaging) were retrospectively analyzed. The primary endpoint was the incidence of lymphopenia grade ≥ 3 in IMPT vs IMRT treated patients. Results271 patients were enrolled (IMPT: n = 71, IMRT: n = 200) in four centers. All patients received platinum-based chemotherapy. Median age: 66 years, 58 % were male, 36 % had squamous NSCLC. The incidence of lymphopenia grade ≥ 3 during CCRT was 67 % and 47 % in the IMRT and IMPT group, respectively (OR 2.2, 95 % CI: 1.0–4.9, P = 0.03). The incidence of anemia grade ≥ 3 during CCRT was 26 % and 9 % in the IMRT and IMPT group respectively (OR = 4.9, 95 % CI: 1.9–12.6, P = 0.001). IMPT was associated with a lower rate of Performance Status (PS) ≥ 2 at day 21 and 42 after CCRT (13 % vs. 26 %, P = 0.04, and 24 % vs. 39 %, P = 0.02). Patients treated with IMPT had a higher probability of receiving adjuvant durvalumab (74 % vs. 52 %, OR 0.35, 95 % CI: 0.16–0.79, P = 0.01). ConclusionIMPT was associated with a lower incidence of severe lymphopenia and anemia, better PS after CCRT and a higher probability of receiving adjuvant durvalumab.

Ropeginterferon Alfa-2b for Pre-Fibrotic Primary Myelofibrosis and DIPSS Low/Intermediate-1 Risk Myelofibrosis: Durable Responses and Evidence of Disease Modification

Background Most patients with primary myelofibrosis (PMF) in pre-/early fibrotic stage (pre-PMF) and at low or intermediate-1 risk by the dynamic international prognostic scoring system (DIPSS) will progress to higher risks or overt MF. There is currently no consensus on the optimal treatment for these patients. Ropeginterferon alfa 2b (ropeg) is a next-generation monopegylated interferon alfa-2b developed specifically to treat myeloproliferative neoplasms (MPN). Aims P1101MF is an on-going multicenter phase 2 study of ropeg in patients with pre-PMF and DIPSS low/intermediate-risk PMF. Methods Key eligibility included morphologically confirmed pre-PMF, overt PMF, post-polycythemia vera MF (PPV-MF) or post-essential thrombocythaemia MF (PET-MF), DIPSS low/intermediate-1 risk, and the need for cytoreduction. The primary outcome were responses in haemoglobin (Hb, from 10 g/dL to upper reference range), white blood cell (WBC, &amp;lt; 10 x 10 9/L) and platelet (≤ 400 x 10 9/L) at 24 and 48 weeks. Secondary outcomes included adverse events (AEs), changes in mutant allele frequencies (MAF) of driver and non-driver genes as assessed by droplet digital polymerase chain reaction (ddPCR), quality-of-life (QOL), cytokine profiles and bone marrow morphology. Patients received ropeg at a dose of 250 mcg at week 1, followed by 350 mcg at week 2 and 500 mcg every 2 weeks from week 4 onwards. Results At the data cut-off of 30 June 2023, 37 men and 29 women with a median age of 59 (range: 30-86) years were enrolled. The diagnoses were pre-PMF (=46, 69.6%); overt PMF (N=6, 9.1%); PPV-MF (N=5, 7.5%); and PET-MF (N=9, 13.6%). Mutational profile of driver genes was JAK2V617F (N=46, 69.6%); CALR mutations (type 1/type-1 like, N=13, 19.7%; type 2/type 2-like, N=4, 6.1%); MPL mutation (N=1, 1.5%); and triple-negative (N=3, 4.5%). The median time from diagnosis to treatment was 5.8 (1-271) months. The median baseline parameters were white blood cell count (WBC): 6.49 (3.25-33.95) x 10 9/L; haemoglobin (Hb): 12.5 (7.1-15.9) g/dL; platelet count: 495 (113-1114) x 10 9/L; and lactate dehydrogenase: 277 (136-1146) IU/L. The median follow-up was 69 (4-69) weeks, with 61 patients (92%) and 51 patients (77%) having completed 24 and 48 weeks of treatment respectively. Responses in Hb, WBC and platelet were 75%, 82% and 74% respectively at 24 weeks, and 82%, 80% and 71% respectively at 48 weeks. Reduction of MAF at 24 and 48 weeks was achieved for JAK2V617F in 50% (19/38) of patients (≥50%, N=10, 26%; complete, N=3, 8%) and 79% (22/28) of patients (≥50%, N=6, 21%; complete, N=1, 4%) respectively; and for CALR in 44% (7/16) of patients (≥50%, N=1, 6%) and 50% (5/10) of patients (≥50%, N=1, 10%) respectively. Forty-six patients (69.6%) had bone marrow biopsies serially performed, with 42 patients (91%) having stable/improved marrow fibrosis. Eight patients (17.4%) had resolution of marrow fibrosis by 48 weeks. There were 5 discontinuations (personal reasons, N=1; intractable pruritus, N=1; symptom/spleen size progression, N=3). Disease progression (pre-PMF to overt PMF; development of accelerated/blast phase) was not observed. Non-haematological AEs included transaminitis (grade 1-2, N=34); malaise (grade 1-2, N=27; grade 3-4, N=1) and hair loss (grade 1-2, N=21). The most common haematological AE was anaemia (grade 1-2, N=15; grade 3-4, N=6). Conclusion: Ropeg was well-tolerated, effective in cytoreduction and induced molecular and morphologic responses in patients with pre-PMF and low/intermediate-1-risk MF.

Diagnostic and prognostic impact of preoperative thrombocytosis in muscle invasive bladder cancer: Any role in clinical practice?

Since earlier research suggested a link between preoperative thrombocytosis and poor oncological outcomes in several cancers, the significance of platelet count abnormalities in bladder carcinoma (BC) demands for further investigation. To assess the prognostic value of preoperative thrombocytosis (PTC) on survival in patients with bladder carcinoma treated by radical cystectomy (RC). Analytical cohort comprised a single-center series of 299 patients who underwent RC for bladder carcinoma was evaluated. A platelet count beyond the threshold of 400 × 109 /L was considered thrombocytosis. Along with the Kaplan-Meier survival probability, cox proportional hazard regression models were used. Twenty-eight (9.4%) patients had preoperative thrombocytosis. PTC was associated with gender, tumor stage, tumor grade, lymphovascular invasion, hydronephrosis, anemia (p < 0.001), and hypoalbuminemia (p < 0.001). Preoperative thrombocytosis was strongly linked to worse overall survival (OS) (p = 0.002), and cancer specific survival (CSS) (p = 0.004), according to the Kaplan-Meier method. Throughout the follow-up, a total of 198 (66.2%) patients died, including 170 (56.9%) from BC. For this study population 5-year CSS was 45.8%. Preoperative thrombocytosis was not independently associated with OS (HR 1.168; 95% CI 0.740-1.844; p = 0.504) or CSS (HR 1.060; 95% CI 0.649-1.730; p = 0.816) in multivariate Cox regression analysis. Only tumor stage (HR 2.558; 95% CI 1.675-3.908; p < 0.001), hydronephrosis (HR 1.614; 95% CI 1.173-2.221; p = 0.003), lymph node metastasis (HR 1.555; 95% CI 1.076-2-2.248; p = 0.019), anemia (HR 1.454; 95% CI 1.034-2.046; p = 0.032) and ASA grade (HR 1.375; 95% CI 1.006-1.879; p = 0.046) were independently associated with CSS. In a single-center study of consecutive patients who underwent radical cystectomy for bladder cancer, preoperative thrombocytosis was unable to predict outcomes.