bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reviewing the recurrence rates in stage I-III HR or ER positive breast cancer in obese patients given multi-modal weight loss plan post-treatment with aromatase inhibitors.
Authors: Joseph Matthew , Ahmad Asim , Benton Abigail 
Published: August 2024

15 Background: Aromatase inhibitors (AIs) in the treatment of endocrine recepter positive breast cancer stages I-III, poses significant challenges in the management of obesity. Obesity is not only associated with an increased risk of breast cancer incidence but also with higher rates of cancer recurrence and poorer treatment outcomes. Moreover, the use of AIs, while effective in reducing estrogen levels and preventing ER or HR positive breast cancer recurrence, may exacerbate weight gain and metabolic disturbances in obese individuals. Weight management strategies have experienced increased attention in breast cancer survivors in recent years, especially overweight or obese individuals. Novel data makes it possible to infer that obesity management activities and multimodal programs that incorporate dietary counseling and physical activity can reduce recurrence rates. Methods: Participants in this study were individuals with Stage I-III endocrine receptor positive breast cancer who had completed adjuvant therapy and had a BMI in the 40s or 50s, increasing risk of recurrence. Eligible patients were identified based on the start date for endocrine therapy. High-risk patients were then assigned to either the intervention or control group. Those in the intervention group received access to a dietician, along with informational pamphlets on physiology and weight loss strategies. Additionally, they were offered discounts to certain gyms or provided free access to fitness facilities. Both intervention and control groups were briefed about the study, with those in the intervention group encouraged to utilize the provided resources for weight management. Results: The evidence from our study will underscore the potential benefits of multimodal weight loss interventions in overweight or obese breast cancer survivors, particularly in improving anthropometric outcomes and enhancing overall quality of life. Conclusions: While the studies included in our analysis demonstrated reductions in body weight, BMI, and waist circumference, as well as improvements in quality of life measures, there remains a notable gap in understanding the impact of these interventions on breast cancer recurrence rates, especially in the context of endocrine-positive breast cancer treated with Aromatase Inhibitors (AIs).
Opioid access barriers for cancer pain relief in Vietnam: A qualitative study.
Authors: Nguyen Trang , Pham Tung , Bui Linh , Krakauer Eric Lewis , Phelan Caroline 
Published: August 2024

154 Background: Although the World Health Organization designates opioids as an essential medication and recommends them as the cornerstone for managing moderate to severe cancer pain, their accessibility is severely restricted, particularly in low and middle-income countries. Despite Vietnam's early endeavors in the advancement of palliative care, including a revised opioid prescription policy in 2008, opioid use for cancer pain remains suboptimal, with oral morphine available only in a few major hospitals. To inform comprehensive strategies for improving opioid access, this study aims to explore the views of healthcare providers, regulators, cancer patients, and caregivers in Vietnam on the barriers to safely accessing opioids for cancer pain management. Methods: We conducted a qualitative, descriptive study and recruited five healthcare providers, six cancer patients and caregivers, and six regulators (i.e., policymakers in the Ministry of Health, heads or deputy heads of pharmacy, oncology, or palliative care departments) across Vietnam via purposeful sampling technique. Data were collected using semi-structured interviews, and the audio recordings were transcribed verbatim and subjected to inductive content analysis using a Framework Method. Results: Five categories of barriers were identified: 1) Patient-related barriers (fear of addiction and other side effects, morphine's association with impending death, negative administration experiences, religious beliefs); 2) Professional-related barriers (knowledge and experience deficit, fear of addiction and other side effects, concerns about opioid diversion and associated liabilities, lack of guidance, education, and training); 3) Medicine-related barriers (limited oral morphine availability, limited domestic pharmaceutical manufacturers and suppliers, supply interruptions, poor variety of opioid types and formulations, difficulties accessing parenteral opioids); 4) Services delivery barriers (scarce palliative and home care services); 5) Regulatory barriers (lack of information on opioid distribution channels, difficulties obtaining confirmation letters for patients' opioid usage needs, overly strict regulation enforcement). Conclusions: Barriers to opioid access for cancer pain control in Vietnam are multifactorial and mutually reinforcing, necessitating interdisciplinary solutions to overcome them. This approach should involve enhancing education about the appropriate use and management of opioids, along with current opioid policies for patients, communities, healthcare providers, and regulators; enacting and implementing policies mandating oral morphine availability at local health facilities; expanding palliative care services; utilizing telemedicine; and establishing an electronic opioid prescription monitoring system.
Effectiveness of using risk communication to help smokers with cancer quit smoking: A randomized controlled trial.
Authors: Li William Ho Cheung , Lam David Chi Leung , Sin Kit Man , Wong Eliza Lai Yi , Wong Carlos K H , Loong Herbert H. , Cheung Kai Yeung , Xia Wei , Song Peige , Chung Joyce Oi Kwan 
Published: August 2024

158 Background: Despite evidence that patients living with cancer who continue to smoke after diagnosis are at a higher risk for all-cause mortality and reduced treatment efficacy, many cancer patients continue to smoke. This study aimed to examine the effectiveness of using a brief risk communication approach to help smokers with cancer quit smoking. Methods: A randomized controlled trial was conducted on 528 patients who continued to smoke and were follow-up at five out-patient clinics in Hong Kong. A total of 268 subjects were randomly assigned to the intervention group that received health warnings on smoking, and 260 subjects were randomly assigned to the control group that received usual care. All subjects had follow-up telephone calls at 1week, 1 month, 3 months, 6 months and 12 months to assess smoking status. Results: The biochemically validated quit rate at the 6-month follow-up was higher in the intervention group than in the control group (5.2% vs 3.8%; OR 1.38, 95% CI 0.60–3.16). The rate of at least 50% self-reported reduction of smoking at 6 months, was higher in the intervention group than in the control group (16.8% vs 12.3%; OR 1.43, 95% CI 0.88–2.35).The results showed that many smokers diagnosed with cancer believed that it was too late to quit smoking. Many participants claimed that overcoming cigarette cravings was extremely difficult, and therefore felt that the barriers to quitting outweighed the perceived benefits. Conclusions: It is crucial to proactively implement novel and effective smoking cessation interventions for smokers with cancer. Importantly, it will help to improve the physical well-being and health-related quality of life of smokers with cancer and protect the public, especially vulnerable groups such as women and children, from exposure to second-hand smoke. This will ultimately save more lives, protect the environment, and boost sustainable development. Clinical trial information: NCT01685723 .
Stereotactic centralized ablative radiation therapy: A novel methodology in treating bulky tumor and its technical realization.
Authors: Yang Jun , Yan Weisi , Lu Qiuxia , Han Liangfu , Wang Brian 
Published: August 2024

159 Background: Bulky tumors pose significant challenges to traditional treatment modalities such as surgery, chemotherapy, and conventional radiotherapy. This study introduces a novel therapeutic approach named as Stereotactic-Core-Ablative-Radiation-Therapy (SCART), designed to deliver an ablative dose to a substantial core of the bulky tumor while quickly decreasing to a lower dose at the tumor periphery. Methods: A SCART-Treatment-Volume (STV) at the core of the GTV was predefined to administer an ablative radiation dose, aiming to induce DNA damage in cancer cells and potentially trigger biological cancer-killing effects. Utilizing Linac-based VMAT or Cyberknife techniques with 6MV photon beams, multiple radiation fields intersect and optimize at STV, generating an ablative dose at the STV. The dose rapidly diminishes to a safe level at the edge of GTV sparing the surrounding tissue. In the phase-1 trial, nineteen patients with 21 bulky tumors enrolled, receiving SCART at five dose levels (15GyX1, 15GyX2, 15GyX3, 18GyX3, 21GyX3, and 24GyX3), while maintaining the GTV's peripheral dose at 5Gy each fraction. Results: All patients completed treatment with average beam-on time of 8.9min and average treatment time of 18.5min. Mean follow-up time is 15.4 month. No grade-III or higher toxicity was observed. 7/19 patients still survive, with the overall survival of 40% at 30 months. Mean tumor volume shrinks by 60% between initial 301cc and post-SCART volumes of 118cc. Long-term follow-up revealed that 14/21 tumors achieved Partial Response, 2/21 Complete-Response, 3/21 Stable-Disease, and 1/21 Progressive-Disease, leading to an encouraging local control of 95%. Conclusions: SCART emerges as a safe and effective strategy for treating bulky malignant tumors, demonstrating excellent local control and overall survival. Multiple treatment courses were feasible. The results from phase-1 study suggest that SCART could revolutionize the treatment landscape for bulky tumors, offering a promising avenue for further exploration and application in clinical practice.
OncoGPT: An AI assistant for genomic-driven precision oncology.
Authors: Ding Samuel , Xing Xiao-Ming , Ding Yan , Huang Qin 
Published: August 2024

160 Background: Cancer patient’s unique genomic profile can help oncologists select a course of precise personalized treatment for the subject. High throughput next-generation sequencing (NGS) technology allows us to identify genomic alterations simultaneously within a patient’s tumor tissue and blood-circulating tumor DNA (ctDNA) in a single test, however, robust tool for accessing mutation-treatment matching is limited. Methods: OncoGPT was built on a cloud-based elastic computing platform. The NGS data analytical module consists of a cascade of computational algorithms for NGS data processing and gene variant calling. The interactive and univariate Cox proportional hazards models were used for mutation-treatment matching and prognostic effect analysis, respectively. Machine learning algorithms including decision tree, random forest, and neural network were trained and tested with novel features for tissue-of-origin (TO) classification across 8 caner types. Results: We built an AI-driven NGS data analytical platform by integrating computational models, matching algorithms and variant annotation databases to highly accurate achieve cancer-related gene mutations, copy number variation, and structure variants using NGS data from 35,122 tumors across 8 cancer types from three institutions. Next, an AI-driven TO classifier was developed and achieved a weighted F1 score of 0.926 for high confidence predictions (≥ 0.9) on tumor samples. Furthermore, augmented AI matching algorithms were applied to match the optimal personalized treatment and provide prognostic prediction for cancer patients with significantly bett survival outcomes (hazard ratio (HR) = 0.326; 95% confidence interval (CI) = 0.213–0.565; P = 2.52×10−5). Conclusions: We have successfully developed an innovative intelligent system (OncoGPT) with AI capabilities to help accurately find actionable targets from patient tumor or blood ctDNA NGS sequencing data and precisely match individualized therapeutic and clinical trial options for patients. In addition, OncoGPT classified primary tumor sites across 8 different cancer types with high confidence predictions. We believe that OncoGPT would help clinicians make optimal treatment decisions for cancer patients through genomic-driven precision oncology.
Therapeutically targeting the CALR/CD47 pathway in MPN to reactivate natural immunosurveillance mechanisms within the body to enhance treatment outcomes.
Authors: Rinaldi Ciro Roberto , Simmonds Matthew , Walker Claire , Amirian Niloofar , Musleh Moradalden , Squires Anya Megan 
Published: August 2024

170 Background: MPNs are a group of related myeloid malignancies characterized by alterations in mature blood cell production/bone marrow environment and have a tendency to evolve into acute myeloid leukaemia. We demonstrated that CD47 blockade in combination with ruxolitinib, increased CALR expression enhancing cytotoxicity in vitro, promoting enhanced neoplastic clone clearance. With this study we describe a potential methodology for assessing effect of new compounds or combinations and the impact of modulating the immunoresponse upon myeloid malignant clones. Methods: Utilising HEL 92.1.7 and SET-2 cells (JAK2 mutated), Marimo cells (CALR mutated) and K562 cell line models; we will incubate with routine therapies (hydroxyurea, anagrelide, ruxolitinib) in combination with a range of anti-CD47 compounds (Anti-CD47 monocloncal antibodies, BET-1 inhibitors, SIRa inhibitor) and will determine the impact upon CD47 and CALR cell surface expression via flow cytometry. Monocyte derived macrophage (MDM) will be produced through Phorbol 12-myristate 13-acetate (PMA) differentiation of a monocytic Thp-1 cell line. Expression of macrophage cell surface markers (CD11b, CD14), as well as intracellular markers (CD68), will be detected by flow cytometry. MDM will then be polarized to either a pro-inflammatory M1, or anti-inflammatory M2 phenotype, with lipopolysaccharide/interferon gamma or interleukins 4 and 13, respectively. Co-culture experiments will then be undertaken to determine how different anti-CD47 therapy combination impact macrophage polarization and destruction of MPN cell lines. Results: We predict that CALR/CD47 levels on each cell line subtype will respond differently highlighting heterogeneity within MPNs and demonstrating the clear need for a more personalised immunotherapy approach. Alterations in JAK/STAT pathway and BET inhibition may hinder macrophage polarisation to the anti-tumorigenic M1 macrophage phenotype. We theorise that indirect co-culture of M1 macrophage with MPN suspension cells under different treatment modalities will enhance MPN cell death and decrease CD47 expression to a greater level than that which we expect to see in M2 polarised macrophage. We also anticipate that the M2 polarised macrophage, which dominate in the tumour microenvironment as MPN progresses, will fail to phagocytose MPN cells and may not be rescued by novel immunotherapeutics. Conclusions: Our group demonstrated the role of CD47 and CALR expression as a key mechanism and a potential target to enhance presentation of the cancer cell to the immune system, and we believe that understanding the interaction of CD47/CALR – macrophages, will drive new therapeutical approaches able to modulate the immune response and improve patients outcomes, potentially leading to complete MPN clone eradiation and cure.
In-hospital outcome of patients hospitalized for leukemia with comorbid acute decompensated heart failure: An analysis of National Inpatient Sample (NIS).
Authors: Suenghataiphorn Thanathip , Wattanachayakul Phuuwadith , Kulthamrongsri Narathorn , Srikulmontri Thitiphan , Yanpiset Panat , Saowapa Sakditad 
Published: August 2024

173 Background: Recent evidence found increase incidence of heart failure in leukemia patients, influenced by various factors such as the underlying disease and medication usage. Nevertheless, there remains a scarcity of data regarding the in-hospital outcome for individuals admitted for leukemia with comorbid acute decompensated heart failure. Thus, we aim to examine the impact of heart failure on clinical outcomes in leukemia patients. Methods: We utilized the 2020 U.S. National Inpatient Sample (NIS) to investigate patients admitted for leukemia with concurrent diagnosis of heart failure, identified through ICD-10 CM codes. Adjusted odds ratios (aORs) for predefined outcomes were determined using multivariable logistic and linear regression model, adjusting for comorbidities. The primary outcome assessed was inpatient mortality, while secondary outcomes included complications related to various body systems. Results: We identified 43,955 patients with a primary discharge diagnosis of leukemia. The mean age was 54.5 years; 49.7% were female. Caucasians accounted for 66%, followed by African Americans (13%). Of these, 11.86% (5,220/43,955) had a concurrent diagnosis of heart failure. In a survey multivariable logistic and linear regression model adjusting for patient and hospital factors, comorbid acute decompensated heart failure was associated with higher in-hospital mortality (aOR 1.57, 95% CI: 1.2, 1.94, p < 0.001), higher mean length of stay (Beta-coefficient 1.93; 95% CI: 0.65, 3.21, p = 0.003), mean total hospital cost (Beta-coefficient 9,472, 95% CI: 2,339, 16,604, p = 0.004), shock (aOR 2.41, 95% CI: 1.84, 3.15, p < 0.001), sepsis (aOR 1.71, 95%CI: 1.38, 2.12, p < 0.001), acute respiratory failure (aOR 2.37, 95% CI: 1.96, 2.87, p < 0.001), and acute kidney injury (aOR 1.57, 95% CI: 1.32, 1.85, p < 0.001). Conclusions: Our study revealed that hospitalized leukemia patients with concurrent heart failure experience higher risk of in-hospital mortality and various adverse in-hospital outcomes. Close monitoring of this factor during hospitalization is essential, and additional longitudinal research is warranted to fully understand this association.
Autologous bone marrow transplant in standard-risk newly diagnosed multiple myeloma: A systematic review.
Authors: Kurniawan Andree , Priantono Dimas , Atmakusuma Tubagus Djumhana , Sari Chandra , Amelia Devi Astri Rivera , Djatnika Deden , Nasution Muhammad Arman , Siregar Nia Novianti , Purlikasari Nugraheny Prasasti , Ariyanti Farieda , Wisman Beta Agustia , Tjhai Patricia Angel , Giselvania Angela , Wijovi Felix , Halim Devina Adella , Heriyanto Rivaldo Steven 
Published: August 2024

174 Background: Multiple myeloma (MM) is a hematological malignancy characterized by clonal proliferation of plasma cells. Bone marrow transplants in high-risk multiple myeloma have been a standard of care for newly diagnosed multiple myeloma (NDMM). Autologous bone marrow transplant (ABMT) has emerged as a promising therapeutic approach for standard risk of NDMM. We aim to review the existing literature on the efficacy of ABMT in standard-risk NDMM in comparison with non-transplant therapeutic approaches. Methods: We conducted a systematic search across PubMed, Google Scholar, Science Direct, and Embase for studies within the last 10 years. We included studies that compared ABMT with other therapies without any history of prior transplants in NDMM patients. We excluded studies that retrospective and case studies. We extracted firstly using PICO: standards risk NDMM, ABMT upfront therapy, progression-free survival, and toxicity. The quality of the study was assessed using the Newcastle-Ottawa scale or JADAD scale questionnaire. Results: Our search yielded 7 studies, with a total of 3728 patients in 7 randomized controlled trial studies. The endpoint was mainly progression-free survival (PFS), with others being response rates and stringent complete response (sCR). All studies consistently showed that ABMT yielded significantly better PFS and response rates in NDMM, with high-dose melphalan being the most common induction regime. ABMT resulted in relatively more severe toxic side effects compared to drugs only. However, the safety profile of ABMT is considered favorable, with manageable adverse events. Induction methods before ABMT include lenalidomide, bortezomib, dexamethasone, carfilzomib, and melphalan, with some studies reporting follow-ups on further maintenance therapy, mainly with lenalidomide. The effectivity of ABMT remains consistent regardless of the drugs used. Conclusions: ABMT is a favorable therapeutic approach for standard risk NDMM with manageable adverse effects and an acceptable safety profile. The effectivity of ABMT is regardless of the concomitant drug used.
Effect of iPSC-derived NK cells with site-specific integration of CAR19 and IL24 at the rDNA locus on anti-tumor activity and proliferation.
Authors: Liang Desheng , Zhang Yuxuan , Shi Qingxin , Hu Qian , Wu Lingqian 
Published: August 2024

175 Background: The generation of CAR-NK cells using induced pluripotent stem cells (iPSCs) has emerged as a paradigm for manufacturing off-the-shelf cell products for universal immunotherapy. However, enhancing the potency, safety and multi-actions of CAR-NK cells is still full of challenges. Methods: Interleukin 24 (IL24) and CD19-specific chimeric antigen receptor (CAR19) were site-specifically integrated at the ribosomal DNA (rDNA) locus in human iPSCs by using TALENickases. The engineered iPSCs were differentiated into NK (CAR-iNK) cells by adopting a 38-day differentiation protocol followed by expansion using magnetic beads in vitro. Results: Compared with the CAR-iNK cells, IL24 armored CAR-iNK (CAR19-IL24-iNK) cells showed higher cytotoxic capacity and amplification ability in vitro. Meanwhile, CAR19-IL24-iNK cells inhibited tumor progression more effectively and exhibited better survival without significant side effects in the B-ALL (Nalm-6(Luc1))-bearing mouse model. Interestingly, RNA-sequencing analysis suggested that IL24 may enhance iNK cell function by attracting neutrophils and upregulating FAS and TNFSF10-related genes while exerting a direct effect on tumor cells. Conclusions: This study encourages the exploration of IL24 and other molecules to enhance antitumor properties of CAR-NK cells, suggesting a novel strategy to modulate tumor microenvironment while attacking tumor cells with the potential of promising off-the-shelf immunotherapy.
Enhancing awareness and efficacy of palliative care consultation through educational intervention among healthcare professionals in a tertiary hospital: A promotional education study.
Authors: Choi Youn Seon 
Published: August 2024

186 Background: Palliative Care Consultation (PCC) has demonstrated efficacy in augmenting patient quality of life, diminishing hospitalization durations, lowering medical costs, and improving survival outcomes. Despite its benefits, there still remains low awareness of PCC in Korea, with healthcare professionals (HPs) treating terminal cancer patients often lacking knowledge about it. Thus, we aimed to assess the awareness of PCC among HPs in a tertiary hospital, subsequently implementing targeted educational interventions to ascertain their impact through a survey. Methods: Face-to-face instructional session focusing on PCC was administered to HPs by palliative care professional. The datasets from pre- and post- education questionnaires of a cohort comparing 120 participants were subjected to analysis. Utilizing t-test, we evaluated the statistical significance of score variations observed before and subsequent to the educational intervention. Results: Within the participants, 61.7% of the HPs reported having experience with PCC. Preliminary survey results indicated that 11.8% were “Completely unaware” of PCC, while 37.8% possessed “unaware”. The mean scores demonstrated an improvement in knowledge of PCC from 18.04 pre-education to 19.84 post-education. ( P=0.003). Conclusions: Through promotional education, an enhancement in knowledge levels regarding PCC was observed. Emphasizing sustained concern in CPC is essential to ensure that palliative care recipients receive appropriate care at the optimal time.