tbuckley/cabot-search huggingface dataset:
Cost-effectiveness of liquid biopsy for molecular profiling of newly diagnosed advanced non-squamous NSCLC in an Asian population.
Authors: Aaron C. Tan, Sibo Liu, Nicholas Graves
Journal: Journal of Clinical Oncology (2024)

178 Background: Liquid biopsy is complementary to tissue biopsy for lung cancer profiling, yet evidence of the cost-effectiveness is limited. This could retard implementation and reimbursement in clinical practice. The aim of this study is to estimate the cost-effectiveness of profiling strategies that include liquid biopsy and to identify the optimal profiling approach for newly diagnosed advanced non-squamous non-small cell lung cancer (NSCLC) in an Asian population using Singapore as an example. Methods: A decision tree and partitioned-survival model was developed from the Singapore healthcare system’s perspective to evaluate the cost-effectiveness of five molecular profiling strategies: either tissue or plasma next-generation sequencing (NGS) alone, a concurrent, and two sequential approaches. Model inputs were informed by local data or published literature. Sensitivity analyses and scenario analyses were undertaken to understand the robustness of the conclusions for decision making. The optimal strategy at different willingness-to-pay (WTP) thresholds was presented by cost-effectiveness acceptability frontier and the expected loss curve. Results: The sequential tissue-plasma NGS approach revealed an additional 0.0981 quality adjusted life years (QALYs) for an extra cost of S$3,074 over a 20-year time horizon compared to tissue NGS alone, resulting in an incremental cost-effectiveness ratio (ICER) of S$31,318/QALY and an incremental net monetary benefit of S$1,343 per patient. The findings were sensitive to the costs of pembrolizumab and osimertinib and the probabilities of re-biopsy after tissue NGS. Sequential plasma-tissue NGS and plasma NGS alone were more costly and less effective than alternatives. Conclusions: The sequential tissue-plasma NGS approach generated the highest net monetary benefit and was the optimal testing strategy when WTP was S$45,000/QALY. It retained superiority but understandably with a higher ICER when expensive, non-first line treatments were included. Overall, its routine clinical practice should be proactively considered for newly diagnosed advanced non-squamous NSCLC in an Asian population.
COVID-19 infection impact on race and clinical outcome of patients with breast cancer: A nationwide analysis.
Authors: Thanathip Suenghataiphorn, Narathorn Kulthamrongsri, Tuntanut Lohawatcharagul, Chalermkiat Kansuttiviwat, Sakditad Saowapa
Journal: Journal of Clinical Oncology (2024)

16 Background: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in females worldwide. Recent data showed the detrimental effects of COVID-19 infection on other neoplasm conditions, causing increased mortality rates and complications. However, limited information exists on the specific impacts of COVID-19 infection in patients hospitalized for breast cancer, as well as racial impact differences. Methods: We analyzed the 2020 U.S. National Inpatient Sample (NIS) to investigate the effects of COVID-19 infection on cases primarily admitted due to breast cancers. Adjusted odds ratios (aORs) for specified outcomes were calculated through multivariable logistic and linear regression analyses. The primary outcome was inpatient mortality, with secondary outcomes including system-based complications. Statistical significance was established at a p-value of 0.05. Results: We identified 25,559 patients with a primary discharge diagnosis of breast cancer. The mean age was 59.7 years; 99.28% were female. In the non-COVID group, Caucasians accounted for 60%, followed by African Americans (19%). However, in the COVID-19 group, African Americans predominated with 41%, followed by Caucasian (35%) (p-value = 0.05). Of these, 0.52% (85/25,559) had a concurrent diagnosis of COVID-19 infection. In a survey multivariable logistic and linear regression model adjusting for patient and hospital factors, COVID-19 infection was associated with higher in-hospital mortality (aOR 6.07; 95% CI (1.26, 29.13), p = 0.024), higher mean length of stay(b 5.22; 95% CI (2.08,8.36) p =0.001), acute respiratory failure (aOR 4.88; 95% CI (1.51, 15.77), p = 0.008), coagulopathy (aOR 8.38; 95% CI (2.19, 32.02), p=0.002) and SIRS (aOR 6.38; 95% CI (1.25, 32.50), p = 0.026). We observed non-significant, but increased, risks of acute kidney injury (AKI), shock, and sepsis, as well as total hospitalization costs in COVID-19-positive patients. Conclusions: In conclusion, our study underscores that COVID-19 infection is associated with higher in-hospital mortality and other clinical outcomes in breast cancer patients, as well as, a disproportionated impact against some races. Future longitudinal studies are warranted to comprehensively assess the causation of these clinical outcomes in this population.
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: Fengyan Li, Guan-Qun Zhou
Journal: Journal of Clinical Oncology (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 ( χ 2 ) 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 &lt; 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.
The impact of HRD mutation on survival in patients with <i>KRAS</i>-mutated advanced pancreatic cancer: A real-world database study.
Authors: Yusuke Kawanaka, Chiaki Inagaki, Takayuki Takahama, Satomi Watanabe, Seiichiro Mitani, Junko Tanizaki, Kaoru Tanaka, Takeshi Yoshida, Tsutomu Iwasa, Hisato Kawakami, Kazuko Sakai, Kimio Yonesaka, Kazuto Nishio, Kazuhiko Nakagawa, Hidetoshi Hayashi
Journal: Journal of Clinical Oncology (2024)

221 Background: Advanced pancreatic ductal adenocarcinoma (PDAC) is associated with a poor prognosis. Prior studies indicate that homologous repair deficient (HRD+ve) PDAC patients (pts) have improved survival and greater response to platinum agents, but the optimal treatment for these population is still unclear. Here, we evaluate the survival impact of HRD mutations in KRAS-mutated PDAC, which represent 90% of cases, in a real-world setting. Methods: We retrospectively reviewed all pts diagnosed with KRAS-mutated PDAC from Jun 2019 to Dec 2021, who were registered in the Center for Cancer Genomics and Advanced Therapeutics (C-CAT), the cancer registry with comprehensive genomic profiling (CGP) data. Pts were stratified with the presence or absence of HRD mutations identified through Foundation One, including ATM, ATR, BRCA1, BRCA2, BRIP1, CHEK2, FANCA, PALB2, and RAD51. We analyzed the prevalence of co-alterations and the impact of HRD status on survival. Pts with a history of systemic therapy for curative intent were excluded from the survival analysis. Results: In 2251 PDAC cases (HRD+ve 232pts, HRD-ve 2019pts) enrolled, we found that HRD+ve PDAC had a significantly lower incidence of TP53 mutation (p&lt;0.001), CDKN2A mutation (p&lt;0.046), and CDKN2A loss (p&lt;0.046). Survival analysis was performed in 823 pts (HRD+ve 92pts, HRD-ve 731pts). HRD+ve pts had significantly longer overall survival (OS, 28.8m vs 23.5m, P=0.030). In the first line setting, HRD+ve pts had exhibited a markedly extended time-to-treatment failure (TTF; [HRD+ve, 19pts vs. HRD-ve, 177pts]; 7.6m vs. 5.4m; p=0.026) and OS ([HRD+ve, 30pts vs. HRD-ve, 239pts]; 28.8m vs. 23.5m; p=0.019) when treated with mFOLFIRINOX (mFFX), but not when treated with gemcitabine plus nab-paclitaxel (GA; [HRD+ve, 34pts vs. HRD-ve 276pts]; OS, 29.3m vs 26.3m; p=0.34; TTF, 5.2m vs. 5.2m; p=0.80). In the second line setting, there were no differences in TTF between HRD+ve and HRD-ve irrespective of these regimens. Among HRD+ve PDAC pts, pts who having received mFFX tend to have better survival compared to those who did not (46pts vs. 46pts; OS, 31.7m vs 26.3m; p=0.09). Conclusions: Our analysis has identified a unique profile in HRD+ve PDAC, underscoring the importance of platinum-based chemotherapy in the initial treatment to enhance survival, which highlights the practical clinical benefits of routine CGP for pts with KRAS-mutated PDAC.
Early circulating tumor DNA (ctDNA) changes during treatment with immune checkpoint inhibitors (ICI) as a predictor of clinical outcomes in patients (pts) with advanced stage melanoma/skin cancer.
Authors: Vincent T. Ma, Yeonhee Park, Janmesh. D Patel, Madison S. Harris, Matthew C. Mannino, Jennifer L. Schehr, Alexander Birbrair, Shuang Zhao, Joshua Michael Lang
Journal: Journal of Clinical Oncology (2024)

225 Background: ctDNA monitoring has shown promising results in predicting relapse in resected solid tumors. Its role in treatment response assessment and predicting survival outcomes in the unresectable or metastatic disease setting merits further investigation. In our study, we attempt to assess the role of early ctDNA changes in predicting disease response, progression, and overall survival outcomes in pts with advanced stage melanoma/skin cancer treated with ICI therapy. Methods: A retrospective analysis using a personalized, tumor-informed ctDNA assay (Natera) on prospectively collected plasma samples from pts with unresectable stage III/IV melanoma/skin cancer treated with anti-PD-1 based therapy at the University of Wisconsin (Madison) was performed. Baseline ctDNA levels were assessed prior to the start of treatment and at 3-4 weeks (i.e. prior to the second treatment dose). A logistic regression model was used to evaluate the odds of overall disease control [complete response + partial response + stable disease, per RECIST version 1.1] based on the change in ctDNA levels (decrease vs increase) between both time points. Cox proportional hazard models were used to investigate the effects of ctDNA level change on progression free survival (PFS) and overall survival (OS). Results: 46 pts were evaluated. 82% melanoma, 14% Merkel cell carcinoma, 2% skin adenocarcinoma and 2% squamous cell carcinoma. 77% were treated with dual ICI (anti-PD-1 based) therapy and 23% with anti-PD-1 monotherapy. Median follow up was 12.1 months. Median change in ctDNA levels from baseline were -4.83 MTM/mL among pts with ctDNA decrease and +37.39 MTM/mL among pts with ctDNA increase. A qualitative decrease in ctDNA level was associated with overall disease control (OR 65.00, 95% CI 11.88-587.89, p&lt;0.0001), longer PFS (HR 0.08, 95% CI 0.03-0.22, p&lt;0.0001), and longer OS (HR 0.17, 95% CI 0.05-0.54, p=0.0008) compared to an increase in ctDNA level from baseline to 3-4 weeks after starting ICI therapy. Median PFS was not reached (NR) and 1.63 months; and median OS was NR and 5.57 months among pts with ctDNA decrease and ctDNA increase, respectively. Conclusions: We found that early ctDNA dynamics after 3-4 weeks of ICI initiation in pts with advanced melanoma/skin cancer appears to be a candidate strategy to predict treatment response, risk of progression, and potentially long-term survival. Larger prospective studies are warranted to validate the utility of ctDNA in treatment monitoring.
The correlation between L1CAM expression and outcomes in patients with metastatic colorectal cancer treated with first-line chemotherapy.
Authors: Andrea Pretta, Flaviana Cau, Pina Ziranu, Dario Spanu, Clelia Donisi, Giusy Moledda, Andrea Cadoni, Erika Cimbro, Sara Murgia, Stefano Mariani, Eleonora Lai, Marco Puzzoni, Valeria Pusceddu, Gavino Faa, Mario Scartozzi
Journal: Journal of Clinical Oncology (2024)

95 Background: L1CAM is a cell adhesion molecule and stem cell marker belonging to the immunoglobulin superfamily of cell adhesion molecules (IgCAMs). L1CAM may be aberrantly expressed in several types of human tumors. The aim of the present study was to evaluate the correlation between L1CAM expression and outcomes in patients with metastatic colorectal cancer. Methods: We retrospectively collected data from 51 mCRC pts treated between 2017 and 2022 at the Medical Oncology Unit of the University Hospital of Cagliari. Tumor samples were retrospectively tested for L1CAM immunohistochemical (IHC) expression with the aim of evaluating the correlation with clinical outcome in terms of overall survival (OS) and progression-free survival (PFS). The primary endpoint was the mOS while secondary endpoint was mPFS. The aim of the present analysis was to evaluate the role of L1CAM expression in tumor cells in predicting the clinical outcome of CRC patients treated with standard chemotherapy. Statistical analysis was performed with the MedCalc Statistical Sofware Version 14.10.2. Results: Median age was 70 (±13), 58.8% were males and 41.2% were females. 29.4% of pts had carcinoma of the right colon, 39.2% left colon and 31.4% rectum. Negative or weak L1CAM score 0 was observed in 39.2% patients; 43.1% pts showed a score 1+; 11.8% showed score 2+, and 5.9% showed score 3+. Positivity for L1CAM correlated with a worse prognosis. The median OS for pts not expressing L1CAM was 74.0 months versus 32.0 for patients expressing the biomarker ( p = 0.0021). The mPFS for patients not expressing L1CAM was 21.0 months, vs 6.0 for patients expressing the biomarker ( p = 0.0066). The same negative correlation on outcomes was shown based on the degree of L1CAM expression. A different L1CAM score corresponded to a different OS and PFS. Pts with score 0 showed a mOS of 74 months vs 37 and 18 months for scores 1+ and 2+/3+, respectively ( p &lt; 0.0001). Similar results were obtained with the mPFS: patients with score 0 showed a median of 21 months vs 8 and 2 months for scores 1+ and 2+/3+, respectively ( p = 0.0138). Conclusions: L1CAM expression in cancer cells correlates with a worse prognosis in mCRC patients. Immunohistochemical evaluation of this biomarker could allow the identification of a subgroup of patients capable of benefiting from a targeted therapy.
Tissue of origin detection for cancer tumor using low-depth cfDNA samples through combination of tumor-specific methylation atlas and genome-wide methylation density in graph convolutional neural networks.
Authors: Nhu Nhat Tan Doan, Trong Hieu Nguyen, Trung Hieu Tran, Thi Hue Hanh Nguyen, Van Thien Chi Nguyen, Hoa Giang, Le Son Tran, Minh Duy Phan
Journal: Journal of Clinical Oncology (2024)

224 Background: Cell free DNA (cfDNA)-based assays hold great potential in detecting early cancer signals yet determining the tissue-of-origin (TOO) for cancer signals remains a challenging task. Here, we investigated the contribution of a methylation atlas to TOO detection in low depth cfDNA samples. Methods: We constructed a tumor-specific methylation atlas (TSMA) using whole-genome bisulfite sequencing (WGBS) data from five types of tumor tissues (breast, colorectal, gastric, liver and lung cancer) and paired white blood cells (WBC). TSMA was used with a non-negative least square matrix factorization (NNLS) deconvolution algorithm to identify the abundance of tumor tissue types in a WGBS sample. We showed that TSMA worked well with tumor tissue but struggled with cfDNA samples due to the overwhelming amount of WBC-derived DNA. To construct a model for TOO, we adopted the multi-modal strategy and used as inputs the combination of deconvolution scores from TSMA with other features of cfDNA. Results: Our final model comprised of a graph convolutional neural network using deconvolution scores and genome-wide methylation density features, which achieved an accuracy of 69% in a held-out validation dataset of 239 low-depth cfDNA samples. Conclusions: In conclusion, we have demonstrated that our TSMA in combination with other cfDNA features can improve TOO detection in low-depth cfDNA samples.
Surufatinib plus toripalimab in advanced soft tissue sarcoma (STS): Results from a multicenter, single-arm, basket study.
Authors: Ying Cheng, Xing Zhang, Ming Lu, Si Shi, Feng Ye, Zhendong Chen, Dongmei Ji, Lijie Song, Fei Yin, Haiyan Shi, Jinghong Zhou, Panfeng Tan, Songhua Fan, Qian Xu, Michael Shi, Weiguo Su
Journal: Journal of Clinical Oncology (2024)

42 Background: Soft tissue sarcomas (STS) are highly malignant despite their low incidence and prone to recurrence, with limited therapeutic options after failure of first-line treatment. Several antiangiogenic monotherapies have shown some efficacy but limited benefit. The open-label, multi-cohort, single-arm, basket study was performed to evaluate the efficacy and safety of the combination of surufatinib (a small-molecule inhibitor of VEGFR 1-3, FGFR1 and CSF-1R) with toripalimab (an anti-programmed death 1 [PD-1] antibody) for Chinese patients (pts) with advanced solid tumors. Here, we reported the results from the STS cohort. Methods: Pts with STS who had progressed on ≤ 2 lines of systemic chemotherapy, or were intolerant to standard treatment, or for whom there was currently no effective therapy were eligible. They received 21-day cycles of surufatinib 250 mg orally, once daily, plus toripalimab 240 mg intravenously, once every 3 weeks, until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per RECIST 1.1. Results: As of data cutoff (Feb 28, 2023), a total of 20 pts (incl. 4 treatment-naïve pts) were enrolled and received the combination treatment (mean duration: 5.81 months [m]). Median (range) age was 50 (23-74) years, 10 pts were male, 17 pts were TNM stage IV. The pathological types include leiomyosarcoma (n=4, incl. 1 naïve patient), synovial sarcoma (n=4), alveolar soft part sarcoma (n=3, incl. 2 naïve pts), undifferentiated pleomorphic sarcoma (n=3), liposarcoma (n=2, incl. 1 naïve patient) and fibrosarcoma (n=1), malignant fibrous histiocytoma (n=1) and others (n=2). Seven (35%) pts had PD-L1 combined positive score of ≥1. The median follow-up duration was 27.14 m. Confirmed ORR and disease control rate (DCR) for 19 efficacy-evaluable pts was 10.5% and 68.4%, respectively; median duration of response was 7.05m. The median progression-free survival (mPFS) and median overall survival (mOS) was 2.69 m and 16.23 m for all dosed pts. For 16 previously treated pts, ORR and DCR was 6.3% and 62.5% respectively; median duration of response (DoR) was 7.13 m; mPFS was 2.65 m; mOS was 14.32 m. 18 (90%) pts experienced at least one treatment-related adverse event (TRAE), and 7 (35%) of them reported grade ≥3 TRAEs. The incidence of immune-related adverse events (irAEs) was 70%, only 2 pts had grade ≥3 irAEs, which were immune-related pancreatitis and immune-related diabetes. 2 pts were permanently discontinued due to TRAEs, which were grade 2 renal impairment and grade 3 hyperglycemia. No new safety signals were observed. Conclusions: Surufatinib plus toripalimab had a promising antitumor activity and a manageable safety profile in pts with advanced STS. Clinical trial information: NCT04169672 .
Navigating the future of pancreatic cancer treatment: Systematic review insights from immunotherapy clinical trials.
Authors: Zouina Sarfraz, Junaid Anwar
Journal: Journal of Clinical Oncology (2024)

68 Background: Pancreatic cancer remains a formidable challenge, being the seventh leading cause of cancer-related deaths globally. Despite advances in medical science, survival rates have not significantly improved, primarily due to late diagnosis and the limited efficacy of conventional treatments. This study investigates the potential of immunotherapy, offering a new horizon for treatment strategies. Methods: A systematic review was conducted, encompassing Phase I-III clinical trials that utilized immunotherapy in treating pancreatic cancer. Databases such as PubMed/Medline, CINAHL, Scopus, and ClinicalTrials.Gov were searched following PRISMA guidelines. A total of 29 completed trials and 106 ongoing studies were analyzed, focusing on survival rates, response to treatment, and adverse events. Results: Analysis of 29 completed clinical trials revealed that immunotherapy could extend the median OS in selected cohorts, with a notable trial showing an increase in OS from 6 to 13.6 months in patients receiving PD-1 blockers. Phase I trials demonstrated a cumulative OS of 13.6 months and a PFS of 5.1 months across various interventions. Ongoing studies, numbering 106, are exploring a wide range of immunotherapeutic agents, aiming to improve these outcomes further. Adverse events were consistent with expectations for immunotherapy, indicating a manageable safety profile. The most promising interventions appear to be combination therapies that include checkpoint inhibitors, showing an increase in the 5-year survival rate of up to 30% for patients undergoing adjunctive treatment post-surgery. Conclusions: Immunotherapy presents a potential paradigm shift in the treatment of pancreatic cancer. However, more robust clinical trials are necessary to fully understand its efficacy and safety. Future research should focus on identifying biomarkers for patient selection and exploring combination therapies to enhance treatment responses. The disparity in access to these therapies, especially in low- and middle-income countries, underscores the need for global efforts to make advanced treatments more accessible.