bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of prognostic factors in uterine cervical malignancy treated with concurrent chemoradiation therapy: A retrospective study in two centers in Korea.
Authors: Lee Seung-Mi , Lee Juhun , Lee Hyun Jung , Song Seungho , Heo Yujin , Lee Jieon , Kim Hee Jung
Published: August 2024

125

Background: Cervical cancer is prevalent in most developing countries, and immune checkpoint inhibitors are very expensive to be standard treatment in limited-resource conditions. In these circumstances, concurrent chemoradiation therapy (CCRT) remains a preferred treatment. This study aims to evaluate prognosis and identify prognostic markers in cervical cancer patients treated with CCRT in Korea. Methods: This retrospective study utilized data from two centers (KNUH and KNUCH) January 2012 to September 2023. Disease stage was determined based on the FIGO 2018 system, including patients between stages IIB to IIIC-2. PET/CT assessed lymph node status. All patients received CCRT as the first-line treatment with cisplatin (40 to 60 mg/m2) chemotherapy and EBRT with or without ICR, guided by gynecologic radiation oncologist. Pelvic MRI or CT within 5 months after CCRT was used to evaluate radiosensitivity, including the size of the residual primary cervical tumor. The primary endpoint was 5-year disease-free survival (DFS), determined via systemic imaging studies like concurrent chest and abdomen CT or PET/CT. Median DFS was evaluated using Kaplan-Meier survival analysis. Prognostic factors were stratified and analyzed using Cox’s proportional hazard ratio regression. Multivariate analysis was conducted using only significant factors identified in the univariate analysis. Receiver operating characteristic curve and Youden’s index were used to determine the cutoff value. Results: Ninety-seven patients were enrolled. The median DFS within 5 years was not reached; mean DFS was 41.5 months (95% CI=36.2–46.8). Multivariate Cox’s proportional hazard regression identified two significant clinical factors for 5-year DFS; residual primary tumor size after CCRT and initial serum CA-125 level (p=0.001, p=0.007, respectively). The cutoff values were 1.85 cm for residual primary tumor size and 24.650 U/mL for CA-125 to predict the 5-year DFS rate (CR or NED vs. PR, SD, PD or recurrence). Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for residual tumor size (36.4%, 98.4%, 92.3%, 73.4%, respectively) and CA-125 (67.9%, 60.7%, 46.3%, and 79.1%, respectively). Conclusions: The size of the residual primary tumor or initial serum CA-125 level can be useful in predicting 5-year DFS rate after CCRT. [Table: see text]
Exploration of the application of the sprayed γ-GGT fluorescent probe for visual imaging of epithelial ovarian cancer.
Authors: Zhang Manlin , Liu Zhihui , Qiu Lin , Ma Wenxin , Yang Zhuo
Published: August 2024

127

Background: To explore the feasibility, accuracy and related influencing factors of spraying γ -GGT fluorescent probe in visual imaging of epithelial ovarian cancer. Methods: This study employed a previously developed spray-type γ-GGT fluorescent probe in fresh ex vivo epithelial ovarian cancer tissues. The experimental group selected ovarian cancer lesions of varying sizes and observed fluorescence imaging after spraying different concentrations of the probe. The optimal imaging concentration and observation time were determined based on pathological results. The validation group then used the optimal parameters to image primary and metastatic lesions, normal tissue, and suspicious areas, confirming the probe's accuracy. Clinical data from patients, such as age and stage, were analyzed to identify factors affecting probe imaging. Results: A total of 16 cases of epithelial ovarian cancer were included in this study, 8 cases were in the experimental group and 8 cases were in the validation group, and the samples were collected from the primary ovarian lesions, omental metastases and peritoneal metastases. In the experimental group, 42 lesions of 3 different diameters were collected. The visible lesions were not found to have any changes in the imaging within 1min-1h after spraying the γ-GGT fluorescent probe, and the SBR value within 1min-1h was between 1.26-1.29, with no statistical difference ( P>0.05), and the visible effect of 5 h was weaker or even invisible to the naked eye, and the best observation time was 1min-1h after spraying the γ-GGT fluorescent probe, and the SBR value of 1min-1h after spraying 10 μM of γ-GGT fluorescent probe was significantly higher than that of 1 μM and 5 μM ( P<0.05), and the best visible effect was achieved by the naked eye, resulting in a minimum effective imaging concentration of 10 μM. A total of 27 points were collected from the lesion with a diameter of <0.3 cm and its surrounding normal tissues with a distance of 1 cm or tissues with a diameter of 1-1.5 cm with a height of suspicion but normal to the naked eye, and 26 of the 27 tissues were confirmed by pathology to be cancerous and 1 was non-cancerous, with a true positive rate of 96.3% and a false positive rate of 3.7%. The overall true positive rate of fluorescence imaging was 98.6%. Univariate analysis showed that there were significant differences in the level of preoperative γ-GGT and the SBR value of preoperative treatment (all P<0.05), and the results of multivariate analysis showed that preoperative treatment was an independent influencing factor for fluorescence imaging of γ-GGT fluorescent probe ( P<0.05). Conclusions: This study tested the γ-GGT fluorescent probe for ovarian cancer imaging, finding 10 μM as the effective concentration and 1 minute to 1 hour as the optimal observation window. The probe's effectiveness is influenced by preoperative treatments.
The prognostic value of deep learning-based percentage of tumour-infiltrating lymphocytes in nasopharyngeal carcinoma.
Authors: Lu Tianzhu , Xie Fei , Zhan Shenghua , Hu Yujun , Zhong Fangyan , Chen Junjun , Pan Jian-ji , Xiong Xiaopeng , Lin Shaojun , Gong Xiaochang , Lin Shaojun , Guo Qiaojuan , Chua Melvin L.K. , Li Jingao
Published: August 2024

133

Background: To calculate the percentage of tumor-infiltrating lymphocytes (TILs) in nasopharyngeal carcinoma (NPC) using deep-learning (DL) algorithms based on digital pathology images and differentiate the outcome. Methods: We recruited 435 patients with primary non-metastatic NPC and 63 patients with de novo metastatic NPC received immunotherapy. TILDL percentage was calculated using the convolutional neural network model, and its ability to differentiate metastasis risk and independent prognostic value were analyzed using Kaplan–Meier survival and multivariate analyses (MVA). Results: The median follow-up time of the training and validation cohorts was 69, and 76 months, respectively. Kaplan–Meier survival analysis showed that the 5-year distant metastasis-free survival (DMFS) and overall survival (OS) of patients with high TILDL were significantly better than those of patients with low infiltration. MVA showed that TILDL degree is an independent prognostic factor for DMFS (training cohort: HR=0.197, 95% CI: 0.077-0.503, p=0.001; validation cohort: HR=0.119, 95% CI: 0.028-0.503, p=0.004) and OS (training cohort: HR=0.418, 95% CI: 0.200-0.873, p=0.020; validation cohort: HR=0.158, 95% CI: 0.048-0.520, p=0.002). The concordance index (C-index) of TILDL was higher than that of the immunohistochemical CD3+, CD8+ T-cell, and CD20+ B-cell densities in terms of the DMFS and OS prediction accuracy. In an immunotherapy cohort of de novo metastatic NPC (n=63), MAV revealed that high TILDL percentage were an independent prognostic factor for PFS (HR=0.368, p= 0.008). Conclusions: TILDL percentage exhibited discriminative capabilities regarding the risk of metastasis and mortality in non-metastatic NPC, and has potential to be a biomarker for dmNPC received immunotherapy. This model will help select patients with a high risk of metastasis and provides a reference for improved individualized treatment.
Safety, tolerability, and immunogenicity of WGc-043 in subjects with EBV-positive cancers: Results from an investigator-initiated trial.
Authors: Peng Xingchen , He Xuan , Zhang Weiwei , Huang Hai , Li Xue , Chen Jie , Wei Yuquan , Song Xiangrong
Published: August 2024

139

Background: The Epstein-Barr virus (EBV) persists and spreads after infection in humans, leading to the occurrence and metastasis of a variety of cancers, posing great challenges in the treatment of cancer.. Conventional cancer therapies tend to have limited success and significant side effects. Therefore, there is an urgent need to develop more safe and efficient treatments such as innovative mRNA vaccines, which provide a new approach to cancer immunotherapy. WGc-043, an mRNA vaccine targeting EBV-positive tumor associated antigens, was evaluated for safety, tolerability, and immunogenicity in a prospective, single-center, investigator-initiated study. Methods: The study included 12 patients aged ≥18 with EBV-positive recurrent or metastatic nasopharyngeal carcinoma. Eligibility criteria included at least one measurable lesion, ECOG performance status 0-1, expected survival greater than three months, and no autoimmune disease. Participants were divided into three dose cohorts (25 μg, 50 μg, 100 μg) and received five administrations followed by optional continued monthly treatment of WGc-043 by intramuscular injection. The study assessed safety by adverse event monitoring, immune response based on the peripheral blood and tumor tissue sample analysis and efficacy according to imaging guidelines and irRECIST version 1.1. Results: The study results demonstrated that WGc-043 had a favorable safety profile with only grade 1 or 2 adverse events and fever (4/12) reported as the most common adverse event. Notably, two patients achieved partial response (PR) and five patients had stable disease (SD), highlighting the potential clinical efficacy of WGc-043. In addition, most (91.7%) subjects showed a significant reduction in plasma EBV DNA levels after administration. Immunogenicity analysis using IFN-γ ELISpot showed that 8 (66.7%) of the 12 enrolled patients developed strong specific immune responses against EBV-associated antigens, indicating that WGc-043 is a potent immunotherapy. Conclusions: This exploratory study underscores the safety and potential efficacy of WGc-043 as an mRNA vaccine for EBV-associated cancers, demonstrating its ability to induce specific immune responses and achieve substantial disease control in a challenging patient population, although further studies in larger clinical trials are needed. These results not only support the advancement of WGc-043 as a candidate for immunotherapy in EBV-positive cancers, but also highlight the translational potential of mRNA vaccine technology in the oncology landscape. Clinical trial information: NCT05714748 . [Table: see text]
HYPCON trial: A phase II randomized study evaluating hypofractionated versus conventional adjuvant radiation therapy in head and neck malignancies.
Authors: Ghosh Adrija , Dagar Abhilash , Izzuddeen Yousra , Vivekanandan Abiramasundari , Raj Jaswin , Hazarika Sangeeta , Nair Ambily , Panda Smriti , Sharma Jyoti , Singhal Abhinav , Das Kalpa , Bhasker Suman , Thakar Alok , Mallick Supriya , Sharma Daya Nand , Sharma Aman
Published: August 2024

143

Background: Hypofractionated RT has been established as standard of care at many cancer sites but there is limited data on use of hypofractionated RT for head and neck carcinomas (HNC). The HYPCON trial (CTRI/2023/02/049804) tested to reduce 10 fractions of PORT by delivery of hypofractionated PORT. Methods: Patients of HNC after radical surgery, with intermediate risk factors, were randomized based on site, T and N stage to either standard fractionation arm A (60Gy/30 fractions/6 weeks) or hypofractionated arm B (50Gy/20 fractions/4 weeks) in a 1:2 manner. The minimum sample size for the study was estimated based on a non-inferiority trial design as 120 considering a 10% clinical effectiveness margin and 5% attrition. Treatment allocation was done based on T stage, N stage & HNC subsite. Target delineation included tumour bed with adequate margins (CTV_P) and microscopic lymph nodal (CTV_N) basin at risk. Organ delineation included all DARS. A double arc swallowing-sparing IMRT was used in both arms. The primary endpoint was locoregional control (LRC) at 1 year. Compliance, RT time (RTT), overall treatment time (OTT), progression-free survival (PFS) and overall survival (OS) were calculated in all patients. Acute & late toxicities were recorded as per RTOG scale. Results: 135 patients were enrolled, 45 in Arm A & 90 in Arm B. Majority of patients (96.9%) had oral cavity primary. Most of patients 74.8 % had early-stage disease. Compliance to PORT was 91.1% in Arm A versus 100% in Arm B. Median RTT for Arm A was 43 days (25-73 days) and 28 days (25-43 days) for Arm B (p<0.0001). Median OTT in Arm A was 91 days (70-126 days) and 77 days (57-119 days) in Arm B (p<0.0001). Median follow-up was 12.7 (2.73-23.87) months. One year, LRC was 72.9% vs 91.6% (p=0.007); PFS was 70.6% vs 90.5% (p=0.009) and OS was 88.7% vs 94.5% (p 0.02) Arm A versus Arm B respectively. Grade 3 or higher acute toxicity was seen in 39% in Arm A and 31.1% in Arm B (p=0.374). Grade 3 or higher late toxicity events were noted in 29.2% and 32.2% in arms A and B respectively (p= 0.671). Conclusions: Hypofractionated PORT reduced RTT & OTT and was associated with improved treatment compliance, treatment outcomes (LRC, PFS, OS), and similar acute and late toxicity profile. This is the first study to demonstrate the superiority of hypofractionated compared to conventional PORT delivery for HNC. Clinical trial information: CTRI/2023/02/049804 .
Hypomagnesemia as a predictor of the efficacy of combination EGFR-targeted drugs versus EGFR ADCs alone in HNSCC.
Authors: Jiang Siqing , Liu Hanchun
Published: August 2024

146

Background: EGFR-targeted drugs and ADCs in combination with EGFR-conjugated chemotherapy drugs can both cause hypomagnesemia. However, the predictive value of hypomagnesemia in response to treatment for head and neck squamous cell carcinoma (HNSCC) is unclear. Methods: This study retrospectively analyzed patients who participated in clinical trials of EGFR-targeted drugs and EGFR ADCs for HNSCC and solid tumors, from February 24, 2022, to March 25, 2024. The primary endpoint of the study was time to treatment failure (TTF). Results: This study conducted a retrospective analysis of 68 patients . All patients exhibited normal baseline serum magnesium levels prior to treatment, but following two cycles of treatment, varying degrees of hypomagnesemia were observed among them. Among the 46 patients who received 2 cycles of combination therapy with EGFR-targeted drugs, 33 were hypomagnesemia and 13 were normal serum magnesium, ORR[90.9%vs. 8.5%,(P=0.002)] (Table), TTF [151 days (95% CI: 212-380) vs. 87 days (95% CI: 52-230), HR 0.576 (95% CI: 0.270–1.230,P = 0.021)]. Among the 22 patients who received EGFR ADC alone for 2 cycles, 8 were hypomagnesemia and 14 were normal serum magnesium, ORR [37.5% vs.28.6%, (P=0.549)] (Table), TTF [97.5 days (95% CI: 68-300) vs. 108.5 days (95% CI: 60-160), HR of 0.877 (95% CI: 0.339–2.263; P = 0.547)]. Conclusions: The study demonstrates that, the occurrence of hypomagnesemia is associated with ORR and TTF following two cycles of combination of EFGR-targeted drugs, not observed in patients receiving EGFR ADCs as monotherapy in HNSCC. [Table: see text]
Impact of acute therapeutic toxicities on anxiety during radiotherapy among Chinese patients with newly diagnosed nonmetastatic head and neck cancer: A cross-sectional study.
Authors: Li Fengyan , Zhou Guan-Qun
Published: August 2024

147

Background: Head and neck cancer (HNC) poses a significant threat to both psychological and physical health. This study aimed to depict the anxiety status of Chinese newly diagnosed nonmetastatic HNC patients during radiotherapy (RT) and to examine predictors of anxiety symptoms. Methods: Newly diagnosed nonmetastatic HNC patients who received RT at the Radiation Therapy Center of Sun Yat-sen University Cancer Center from August 23,2023 to August 24,2023 were recruited into this study. Using Zung Self-Rating Anxiety Scale (Zung SAS) to screen anxiety. Twenty-four common acute therapeutic toxicities (18 patient-reported and 6 clinician-rated) were assessed according to European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck 35 (EORTC QLQ-HN35) and Common Terminology Criteria for Adverse Events, fifth version (CTCAE V5.0). Chi-square ( χ2) test and multivariate binary logistic regression stepwise forward selection: likelihood ratio (LR) method were applied to identify factors associated with anxiety. Results: A total of 457 patients were included ultimately. Up to 29.10% of the patients showed varying degrees of anxiety and the average SAS standardized score was 45.66 ± 8.83. Chi-square test manifested that sex, annual household income, fatigue, anorexia, nausea, vomit, pain, dysphagia, sense problems (smell and taste), speech problems, trouble in social eating, trouble in social contact, sexual frustration, teeth problems, difficulty in opening mouth, xerostomia, sticky saliva, coughing, feeling ill, use of analgesics, use of nutritional supplements and weight loss were related to anxiety ( p < 0.05). But multivariate logistic regression only demonstrated fatigue (OR = 3.696, 95% CI = 2.096-6.519), speech problems (OR = 3.247, 95% CI = 1.554-6.783), sexual frustration (OR = 2.029, 95% CI = 1.232-3.341), nausea (OR = 3.075, 95% CI = 1.807-5.234), feeling ill (OR = 2.283, 95% CI = 1.215-4.291), use of nutritional supplements (OR = 1.930, 95% CI = 1.136-3.280) and difficulty in opening mouth (OR = 3.007, 95% CI = 1.081-8.363) as independent predictive factors of anxiety. Conclusions: The Chinese newly diagnosed nonmetastatic HNC patients suffered greatly from anxiety during RT. This study identified the predictive contribution of sociodemographic and clinical characteristics and 24 common acute therapeutic toxicities to the vulnerability to anxiety, which can provide evidence and reference for medical staff to carry out psychological intervention.
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

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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.
Validation of a tagalog version of the EORTC PATSAT-C33 and EORTC OUT-PATSAT7 patient satisfaction questionnaires for patients with cancer undergoing outpatient radiotherapy.
Authors: Castillo Michelle Regina , Canal Johanna Patricia , Jamora Kurl , Wong Harroun , Sumndad Al Muzani , Tan Anderson Kirk Nigel
Published: August 2024

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Background: The satisfaction of cancer patients with their care significantly impacts their quality of life. Beyond specific cancer treatments, the delivery of care plays a vital role. Evaluating patient satisfaction with care is increasingly important in oncology due to the prolonged and intensive nature of cancer management. Discussions often focus on medical aspects, neglecting administrative and psychosocial concerns. Patient-centered care involves assessing satisfaction, which reflects perceived quality. Patient satisfaction is now recognized as a key indicator of care quality. Methods: The EORTC developed tools like PATSAT-C33 and OUT-PATSAT7 to assess satisfaction with cancer care. These instruments, translated into Tagalog using a “forward-backward” translation procedure in accordance with the EORTC QOL Study Group guidelines, were validated among Filipino cancer patients undergoing radiotherapy. The tools encompass dimensions like doctors' skills, information exchange, nurses' responsiveness, and care organization. They showed reliability and validity comparable to the original versions. Results: Construct, criterion, and factorial validity were assessed, indicating the tools measure intended constructs effectively. The multi-item scales of EORTC PATSAT-C33 and EORTC OUT-PATSAT7 have good to excellent internal consistency. A value between 0.8 - 0.9 represents good reliability, whereas a Cronbach alpha of≥0.9 represents excellent reliability. Criterion validity was confirmed by comparing them with a validated Filipino satisfaction scale. Each dimension identified in the original study applies to Filipino cancer patients, suggesting the tools' applicability across populations. Conclusions: Despite some demographic biases in the study sample, the translations proved valid and reliable. These Tagalog versions are recommended for use with native Tagalog-speaking Filipino cancer patients. Further studies with larger sample sizes may enhance reliability. [Table: see text]
Dietary pattern and the corresponding gut microbiome in response to immunotherapy in Thai patients with advanced non-small cell lung cancer (NSCLC).
Authors: Sitthideatphaiboon Piyada , Somlaw Nicha , Zungsontiporn Nicha , Ouwongprayoon Pongsakorn , Sukswai Narittee , Korphaisarn Krittiya , Poungvarin Naravat , Aporntewan Chatchawit , Hirankarn Nattiya , Vinayanuwattikun Chanida
Published: August 2024

204

Background: Gut microbiota is considered a key player modulating the response to immune checkpoint inhibitors (ICI) in cancer. The effects of dietary pattern on this interaction is not well-studied. Methods: A prospective multicenter cohort of 95 patients with advanced non-small cell lung cancer (NSCLC) undergoing ICI therapy were enrolled. Stool shotgun metagenomic sequencing was performed. Three-day dietary patterns before ICI were assessed. Patients were categorized as hyperprogressive disease (HPD) if they exhibited a time to treatment failure of <2 months. All others were categorized as non-hyperprogressive disease (non-HPD). The correlation between dietary patterns, gut microbiome, and response to ICI therapy was analyzed. Results: In the multivariate analysis, high abundance of Firmicutes unclassified and the Ruminococcaceae family correlated with significantly diminished progression-free survival (PFS) with HR of 2.40 [ P=0.006] and 4.30 [ P=0.005], respectively. More specifically, within the subset of NSCLC patients treated solely with ICI therapy, high abundance of Intestinimonas and the Enterobacteriaceae family were associated with reduced PFS with HR of 2.61 [ P=0.02] and HR 3.34 [ P=0.005], respectively. In dietary pattern analysis, HPD group showed increased consumption of cholesterol, sodium, and fats beyond recommended levels compared to non-HPD group. This group also displayed a tendency towards higher food pattern scores characterized by significant intake of fat and dairy products. Conclusions: Our study revealed distinct association between the gut microbiome composition and treatment outcomes. Based on these findings, the overall composition of diet may play a pivotal role in ICI therapeutic outcomes. [Table: see text]