tbuckley/cabot-search huggingface dataset:
Radiotherapy alone vs radiotherapy with concurrent chemoradiotherapy in patients with low-risk nasopharyngeal carcinoma: Updated results from a multicenter, open-label, non-inferiority, randomized phase III trial.
Authors: Rui Guo, Yuan Zhang, Ning Zhang, Bin Deng, Zhi-Bin Cheng, Jing Huang, Fan Zhang, Yan-Ping Mao, Wen-Fei Li, Guan-Qun Zhou, Yu-Pei Chen, Cheng Xu, Li Lin, Wei-Wei Zhang, Xu Jiang, Qing Liu, Ying Sun, Jun Ma, Lei Chen
Journal: Journal of Clinical Oncology (2024)

142 Background: There is limited evidence for the role of concurrent chemotherapy with use of intensity-modulated radiation therapy (IMRT) in low-risk stage II/T3N0 Nasopharyngeal Carcinoma (NPC) patients. We previously reported comparable 3-year failure-free survival-free survival (FFS) using radiotherapy alone compared with concurrent chemoradiotherapy in the low-risk patients. Here, we present the 5-year overall survival (OS) analysis and additional analysis. Methods: This multicenter, open-label, randomized, phase 3, noninferiority clinical trial was conducted at 5 Chinese hospitals, including 341 adult patients with low-risk NPC, defined as stage II/T3N0M0 without adverse features (all nodes &lt;3 cm, no level IV/Vb nodes; no extranodal extension; Epstein-Barr virus DNA &lt;4000 copies/mL), with enrollment between November 2015 and August 2020. This trial is registered with ClinicalTrials.gov, number NCT02633202. Results: In this randomized trial, patients were assigned to be treated IMRT alone (n=172) or with concurrent chemoradiotherapy (IMRT with cisplatin, n=169). With a median follow-up of 70.1 months, the IMRT-alone group had a similar 5-year overall survival (95.2% vs. 98.2%, hazard ratio, 2.27 [95%CI:0.70-7.40]; P=0.16), failure-free survival (86.2% vs. 88.4%, hazard ratio, 1.16 [95%CI:0.64-2.07]; p = 0.63). Hearing impairment (HI) data (assessed by The Hearing Handicap Inventory for Adult- Screening version (HHIA-S)) were collected from 86 patients in the IMRT-alone group and 81 patients in the concurrent chemoradiotherapy group. Among the patients, 45(26.9%) developed HI (IMRT-alone vs. CCRT: 20 [23.3%] vs. 25 [30.9%]), among which 36 (21.6%) had mind HI (IMRT-alone vs. CCRT: 15 [17.4%] vs. 21 [25.9%]). Conclusions: Radiotherapy alone provides comparable survival or disease control and less toxicity compared to CCRT in low-risk nasopharyngeal carcinoma. Clinical trial information: NCT02633202 .
A phase I/II study of nanoliposomal irinotecan and carboplatin in patients with advanced or metastatic, poorly differentiated gastroenteropancreatic neuroendocrine carcinoma characterized by tissue and liquid next-generation sequencing.
Authors: Nai-Jung Chiang, Chien-Feng Li, Li-Yuan Bai, Chien-Jui Huang, Chih Chieh Yen, Chin-Fu Hsiao, Li-Ching Wu, Ming Huang Chen
Journal: Journal of Clinical Oncology (2024)

52 Background: For locally advanced or metastatic gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs), standard chemotherapy typically incorporates etoposide or irinotecan plus platinum agents. Herein, we initiate a phase I/II trial to apply Nal-IRI in combination with carboplatin as the 1 st line treatment in patients with GEP-NECs to define the dose-limiting toxicity (DLT) and recommended phase II dose (RP2D). Methods: In the phase I part, traditional 3+3 design was applied. Enrolled patients would receive escalating dose of 60 (level -1), 80 (starting dose, level 0) or 100 (level 1) mg/m 2 salt-form nal-IRI plus carboplatin AUC=4 with maximum total dose of 600 mg on D1, every 21 days as a cycle. DLTs were evaluated during the first one cycle of treatment with tumor assessment every 6 weeks. Prophylaxis G-CSF was not allowed in the first cycle Paired testing of tissue (TBx) and liquid biopsy (LBx) was done by Illumina TSO500 platform before treatment. The second LBx would be repeated for confirmed partial responders when progression. Results: Totally 6 GEP-NEC patients with primary sites of colon in three, and each one in esophagus, ampulla of Vater and pancreas were enrolled to level 0. One patient had DLT of grade 4 neutropenia lasting for 3 days even under salvage G-CSF. Treatment-related adverse events showed grade 3/4 neutropenia (33.4%), grade 2 anemia (16.7%), grade 3 fatigue (16.7%), and grade 2 skin rash (16.7%). Four patients achieved confirmed partial response and 2 patients got stable disease, with the objective response rate of 66.7% (95% confidence interval: 22%-96%). After the data and safety monitoring board meeting, level 0 was decided as RP2D but not escalation to level 1 because of acceptable toxicity profiles and promising efficacies. Comprehensive genomic profiling showed that driver mutations were identified in three cases including two harboring BRAF V 600E mutation and one with KRAS G12D mutation. The other three cases lacking driver mutation showed frequent copy number alteration including 1 with MDM2 amplification (copy number 27) and a wild-type TP53. Homologous recombination deficiency (HRD), as determined by GIS score, was identified in a colon GEP-NEC who remained to be HRD-positive at progression but a higher TMB (from 4.7 to 10.2 Muts/Mb) and a higher BRAF V 600E mutation allele frequency (from 24.1% to 43.6%) in tumor tissue, compared to the baseline profiling. Conclusions: Based on current data, the RP2D is 80 mg/m 2 of nal-IRI (salt-form) and carboplatin of AUC=4, every 3 weeks. The extension phase II study in GEP-NEC is ongoing. Clinical trial information: NCT05385861 .
Association of aberrant expression of CD39 with the outcome of patients with cholangiocarcinoma.
Authors: Bohao Zheng, Xiaojian Ni, Houbao Liu
Journal: Journal of Clinical Oncology (2024)

93 Background: Cholangiocarcinoma is defined as a kind of malignant tumor originating from bile ducts. Due to the lack of effective diagnostic and treatment methods, the prognosis of cholangiocarcinoma is dismal. Accumulating evidence indicates that CD39 could promote the progression of several types of cancer. However, the biological function and the underlying mechanism of CD39 in cholangiocarcinoma have not been well investigated. Methods: Quantitative reverse transcription PCR (RT-qPCR), western blot (WB), and immunohistochemistry staining was used to evaluate the expression level of CD39 in cholangiocarcinoma. Kaplan-Meier and Cox hazard ratio regression analyses were implicated to evaluate the prognostic significance of CD39. Cell counting kit-8 (CCK-8) was carried out to evaluate the proliferative capacity, while transwell assay was used to detect the migration and invasion ability. In addition, B-NDG mice were used for the in vivo assay. The potential protein binding with the CD39 was identified through co-immunoprecipitation. Results: We observed that CD39 was aberrantly expressed in the tumor tissue and cholangiocarcinoma cell lines. Our analysis indicated that the high expression level of CD39 correlated with aggressive clinicopathological characteristics, and CD39 was identified as an independent poor prognostic factor in cholangiocarcinoma. In addition, our in vitro and in vivo data indicated that the knockdown of CD39 could suppress the proliferation, migration, invasion ability, and the epithelial-mesenchymal transition (EMT) process of cholangiocarcinoma. Opposite results were observed when CD39 was overexpressed. Mechanistically, CD39 could bind with Annexin A2 (ANXA2), which influences the phosphorylation level of ANXA2 at the Tyr24 site, thereby promoting the activation of PI3K/AKT signaling, which resulted in the biological change in cholangiocarcinoma. Conclusions: Our data indicated that CD39 was overexpressed in the tumor tissue. Meanwhile, CD39 was identified as an independent prognostic factor of poor overall survival for patients withcholangiocarcinoma. In terms of the biological role of CD39, our data indicated that CD39 promoted the progression and metastasis of cholangiocarcinoma through binding with ANXA2, and through activating the PI3K/AKT signaling. In brief, CD39 is a potential prognostic factor and therapeutical target for cholangiocarcinoma.
Enhancing awareness and efficacy of palliative care consultation through educational intervention among healthcare professionals in a tertiary hospital: A promotional education study.
Authors: Youn Seon Choi
Journal: Journal of Clinical Oncology (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.
Predicting chemotherapy response in patients with advanced or metastatic pancreatic cancer using machine learning.
Authors: Moonho Kim, Gyucheol Choi, Jamin Koo
Journal: Journal of Clinical Oncology (2024)

60 Background: When determining the initial chemotherapy regimen for advanced or metastatic pancreatic cancer, various factors must be evaluated. The decision between FOLFIRINOX and Gemcitabine/Nab-paclitaxel (GnP) is challenging, as patient survival hinges on the efficacy and toxicity profiles of these treatments, alongside individual patient characteristics and vulnerabilities.This study aims to guide the selection of an appropriate first-line chemotherapy regimen for advanced or metastatic pancreatic cancer by leveraging machine learning (ML) methods to predict survival outcomes. Methods: We conducted a retrospective analysis involving a cohort of 151 patients who underwent systemic chemotherapy for advanced or metastatic pancreatic cancer at Gangneung Asan Hospital in South Korea between 2019 and 2023. The initial data consisted of 17 types of demographic and clinical characteristics, as well as time-course of response and survival outcomes. The ML models predicting overall survival (OS) were developed using the XGBoost method. The minimal set of covariates resulting in the highest predictive performance during 5-fold cross validation were chosen as inputs to each model. Results: The median age of the patients was 66 years, with 62.3% being male. The ML models achieved the ROC-AUC of 0.81 when predicting OS after 12 months following the initial administration of FOLFIRINOX (n=61) or GnP (n=47). Five (peritoneal metastases, other metastases, bilirubin level, white blood cell counts, and retroperitoneal lymph node metastases) or four (age, tumor location, sex, and metastatic status) covariates were used to achieve the predictive accuracy for the two regimens, respectively. The median OS of the high versus low risk groups of FOLFIRINOX predicted by the ML models were significantly different (7 vs 18 months, P &lt; 0.01), recording the hazard ratio (HR) of 2.79 (95% CI, 1.47-5.26). Similarly, the median OS of the high and low risk groups of GnP were significantly different (8 vs 16 months, P &lt; 0.001, HR 3.50, 95% CI, 1.60-7.66). Conclusions: We developed the ML models that can compute the probability of OS based on the routinely collected data from patients with advanced or metastatic pancreatic cancer. To the best of our knowledge, this is the first ML solution aimed at aiding clinicians in the selection of the first-line chemotherapy regimen for pancreatic cancer.
Comprehensive validation of a cell-free DNA-based assay for multi-cancer detection: A Vietnamese longitudinal prospective cohort study of 9,024 participants.
Authors: Le Son Tran, Thi Hue Hanh Nguyen, Luu Hong Dang Nguyen, Trong Hieu Nguyen, Thanh Dat Nguyen, Hoa Giang, Minh Duy Phan, Duy Sinh Nguyen, Hung Sang Tang, Hoai-Nghia Nguyen
Journal: Journal of Clinical Oncology (2024)

102 Background: Blood-based multi-cancer early detection (MCED) has emerged as a promising method for enhancing early cancer detection efficiency and benefiting population health. However, the lack of evidence regarding their clinical utility across diverse populations has hindered their routine use. To address this, we conducted a comprehensive analytical and clinical validation of an MCED test, SPOT-MAS (Screening for the Presence Of Tumor by DNA Methylation And Size). Methods: Analytical validation was conducted on a retrospective cohort of 96 healthy and 169 cancer-confirmed individuals to determine the limit of detection, reproducibility, and potential interferents. Additionally, we launched a multi-center prospective study, named K-DETEK (ClinicalTrials.gov identifier: NCT05227261), to clinically validate the diagnostic performance. Our study recruited 10,027 asymptomatic individuals aged 40 years or older across 75 major hospitals in Vietnam, following them up for 12 months. Results: SPOT-MAS test demonstrated the capability to detect over 50% of cancer samples with 98% specificity at a tumor fraction of 0.049 (95% CI: 0.043-0.059). These results were consistent across intra- and inter-batch analyses. The test remained robust even with hemoglobin contamination up to 500 mg/dL and genomic DNA contamination of up to 100%. In the K-DETEK study, among 9,024 eligible participants, 43 (0.48%) showed a positive cancer signal. Of those, 25 were diagnosed with cancer through standard imaging and biopsy tests, with 21 matching tumor types with our predictions, resulting in a positive predictive value of 58.14% (95% CI: 43.33-71.62) and tumor-tissue-origin accuracy of 84%. 8,981 participants (99.52%) had a negative cancer signal, and 8,974 were confirmed cancer-free, indicating a negative predictive value of 99.92% (95% CI: 99.84-99.96). The test showed an overall sensitivity of 78.13% (95% CI: 61.25-88.98) and a specificity of 99.80% (95% CI: 99.68-99.87) for cases with tumors at all stages, with slightly lower sensitivity (74.05%, 95% CI: 56.64-87.32) for precancerous and early clinical stages. Conclusions: Our study represents the most comprehensive and largest validation study in Asia supporting the utility of SPOT-MAS as a multi-cancer blood test for early cancer detection. Its potential significance is underscored, particularly in low- and middle-income countries, emphasizing the need for accessible and effective screening tools. Clinical trial information: NCT05227261 .
Stronger together: Implementing patient-reported symptom tool in routine cancer care in diverse Asia—A multi-national pilot feasibility study (PROMiSE-Pilot).
Authors: Piyada Sitthideatphaiboon, Milita Zaheed, Jayson L. Co, Kevin Lee Min Chua, Monica Malik
Journal: Journal of Clinical Oncology (2024)

TPS180 Background: Patients diagnosed with cancer often experience disease or treatment-related symptoms, which can be under-elicited and under-appreciated by clinicians during time-poor consultations. This is particularly challenging in Asia where structural disparities in healthcare access mean oncology services are often under-resourced. Five oncologists from Thailand, India, Singapore, Philippines and Australia formed a working group as part of ASCO Asia-Pacific Leadership Development Program (LDP-AP). Systematic symptom monitoring using patient-reported outcomes measures (PROM) was identified as a potential solution to improve care in diverse Asian settings. PROM has demonstrated improved outcomes in Western settings but its utility in resource limited Asian contexts is less well established. A study was developed to evaluate the feasibility of implementing PROM in routine outpatient care across diverse cultural contexts in Asia. Methods: PROMiSE-Pilot is a prospective, multi-centre, feasibility study of integrating PROM in routine outpatient care across Asia. The Edmonton Symptom Assessment Scale questionnaire (ESAS-r) was selected as the PROM tool. Clinicians in 4 hospitals in Singapore, Manila, Bangkok and Hyderabad will be invited to participate, and their patients will be invited to complete the ESAS-r on paper before each visit. The primary aim is to evaluate if proportion of patients who complete ≥5 of 10 items on ESAS-r is ≥85% (Clopper Pearson). Secondary aims include assessing proportion who complete ≥8 and all 10 items and perceived utility of ESAS-r evaluated through surveys adapted to measure patient and clinician satisfaction. Site-specific patient, clinician, administrative barriers and facilitators will be studied. A pragmatic approach to context-specific implementation was adopted with each site developing its own process map for delivering the pilot and adapting to local patient demographics (e.g. low literacy), cultural contexts and resources. Translated versions of ESAS-r were acquired where necessary. Recruitment commenced in March 2024 following ethics approval at 2 sites. 87 patient encounters have been captured from 5 participating clinicians in Singapore. 5 clinicians have agreed to participate in Bangkok. Target recruitment is 200 encounters per site. Multi-centre data will be presented at the Breakthrough congress. Clinicians from ASCO LDP-AP identified PROM as a low-cost but potentially high-value approach to improving quality of care in resource limited settings in Asia. Understanding the feasibility of such a tool is vital prior to consideration of wider scale adoption by stakeholders. This co-developed multi-national pilot additionally demonstrates the value of collaboration, our strength in diversity and a pragmatic model for investigator-initiated studies in Asia.
Prognostic impact of codon-specific KRAS mutational status on survival in patients with metastatic colorectal cancer treated with TAS-102 or regorafenib.
Authors: Meng-Che Hsieh, Kun-Ming Rau, Kuang-Wen Liu, Chong-Chi Chiu, Chih-I Chen, Ling-Chiao Song, Hsin-Pao Chen
Journal: Journal of Clinical Oncology (2024)

75 Background: Previous study demonstrated KRAS (Kirsten rat sarcoma virus) codon G12 mutation as a potential biomarker of resistance in metastatic colorectal cancer (mCRC). Our study aimed to evaluate the prognostic impact of codon-specific KRAS mutational status on survival in patients with mCRC treated with TAS-102 or regorafenib. Methods: mCRC Patients treated with TAS-102 or regorafenib were retrospectively enrolled into our study. Patients were classified into KRAS G12 (KRAS G12 ) mutation and no KRAS G12 mutation according to extended RAS testing. Survival was estimated for comparison, stratified by KRAS mutational status and treatment. Kaplan-Meier curves were estimated for overall survival (OS). Results: A total of 183 patients were enrolled into our study, with 91 patients treated with TAS-102 and 92 patients treated with regorafenib. The median age was 63 years old in our cohort. Most patients were male (54%) with left side colon (85%). After extended RAS/RAF mutational testing, 28% patients had KRAS G12 mutation, 50% had RAS/RAF WT , 9% had KRAS G13 mutation, 8% had KRAS other mutation, 3% had NRAS mutation and 2% had BRAF mutation. For patients treated with TAS-102 group, 20% patients had KRAS G12 mutation, while for regorafenib group, 38% patients had KRAS G12 mutation. The median OS of TAS-102 was 4.5 versus 11.3 months for KRAS G12 mutation and no KRAS G12 mutation, respectively (p= 0.013). The median OS of regorafenib was 10.5 versus 6.3 months for KRAS G12 mutation and no KRAS G12 mutation, respectively (p= 0.183). Furthermore, 34% patients with KRAS G12 mutation received TAS-102, while 56% patients without KRAS G12 mutation received TAS-102. For patients with KRAS G12 mutation, the median OS was 4.5 m versus 10.5 months for TAS-102 and regorafenib group, respectively (p= 0.113). For patients without KRAS G12 mutation, the median OS was 11.3m versus 6.3 months for TAS-102 and regorafenib group, respectively (p= 0.047). Conclusions: The prognostic impact of KRAS G12 was divergent between mCRC patients treated with TAS-102 and regorafenib. Codon-specific KRAS mutational status should be taken into consideration before treatment.
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: Michelle Regina Castillo, Johanna Patricia Canal, Kurl Jamora, Harroun Wong, Al Muzani Sumndad, Anderson Kirk Nigel Tan
Journal: Journal of Clinical Oncology (2024)

190 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]