tbuckley/cabot-search huggingface dataset:
Impact of gadopiclenol on decision making in patients with brain metastases: A post-hoc study.
Authors: Frank Anton Giordano, Jens Fleckenstein, Miriam Eckl, Florian Stieler, Martin Bendszus, Marco Essig, Frederik Wenz, Gustavo R. Sarria
Journal: Journal of Clinical Oncology (2024)

e14003 Background: Gadopiclenol (Elucirem, Guerbet, France) is a new high relaxivity macrocyclic gadolinium-based contrast agent (GBCA), recently approved by the FDA and EMA at the dose of 0.05 mmol/kg. The aim of this post-hoc analysis was to evaluate the impact of contrast-enhanced MRI with gadopiclenol at 0.1 mmol/kg on decision making and radiotherapy (RT) treatment planning of brain metastases (BM). Methods: This is a post-hoc analysis of data from a phase IIb study where patients underwent two separate MRI examinations, one with gadopiclenol at 0.025, 0.05, 0.1 or 0.2 mmol/kg and one with gadobenate dimeglumine at 0.1 mmol/kg. MR images of patients who received both GBCAs at 0.1 mmol/kg, with ≥1 BM detected in either of the scans, were subjected to a blinded reader analysis and contouring by two radiation oncology experts. For each patient, treatment plans (stereotactic radiosurgery [SRS] or whole-brain radiotherapy [WBRT]) were determined for both MRIs, with the gross target volume (GTV) indicating the contrast-enhancing aspects of the tumor. Mean GTVs and normal tissue volumes receiving 12 Gy (V 12 ), as well as the Dice similarity coefficient (DSC) were obtained for the paired contours. The Spearman´s rank (ρ) correlation was additionally calculated. Furthermore, three experts blindly evaluated the contrast enhancement of each lesion for contouring purposes and subjectively qualified them as “better”, in detriment of the counterpart, or “equal”. Results: In total, images from 13 adult patients were analyzed. MRI with gadopiclenol depicted additional BM as compared with gadobenate dimeglumine in 7 patients (54%). The treatment plan was changed in 2 patients (15%), from no treatment to SRS and from SRS to WBRT. Gadopiclenol depicted additional BM in these 2 patients (from 0 and 10 BM with gadobenate dimeglumine to 1 and 15 BM with gadopiclenol). The mean GTVs and V 12 were comparable between gadopiclenol and gadobenate dimeglumine (p=0.694, p=1.974). The mean DSC was 0.70 (SD: 0.14, ρ0.82). From a total of 36 answers, contrast enhancement was qualified as better with gadopiclenol in 21 (58.3%) evaluations, better with gadobenate dimeglumine in 8 (22.2%) evaluations, while no difference was observed in 7 (19.4%) evaluations. Conclusions: Gadopiclenol at 0.1 mmol/kg improved BM detection and contrast enhancement with potential impact on RT treatment decisions.
Sintilimab combined with definitive chemoradiotherapy in locally advanced esophageal squamous cell carcinoma: A single-arm, multicenter, phase 2 trial.
Authors: Jiahua Lyu, Tao Li, Long Liang, Churong Li, Hongyuan Jia, Yunxiang Qi, Xiumei Zheng, Yu Fan, Hao Kuang, Hansong Bai, Wanli Zhang, Guangbing Lu, Gan Wang
Journal: Journal of Clinical Oncology (2024)

e16120 Background: Sintilimab is a PD-1 inhibitor that is approved for the treatment of advanced esophageal squamous cell carcinoma, but its efficacy and safety in locally advanced disease is unclear. We administered sintilimab with definitive chemoradiotherapy to patients with unresectable locally advanced oesophageal squamous cell carcinoma, and aimed to investigate the efficacy and safety of this treatment pattern. Methods: We conducted a multicenter, phase 2 trial at three cancer centers in sichuan province. Patients aged 18-75 years with untreated, unresectable, stage II-IVA esophageal squamous cell carcinoma, with an ECOG performance status of 0-2, and adequate organ and bone marrow function were eligible for inclusion. Patients received concurrent thoracic radiotherapy (60·0 Gy in 30 fractions), chemotherapy (two cycles of intravenous Albumin-Bound Paclitaxel [180 mg/m2, day1] and cisplatin [25 mg/m2, day1-3]), and Sintilimab (200 mg intravenously every 3 weeks for up to 1 year, or until disease progression or unacceptable toxicity). The primary endpoint was the progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate, quality of life (not reported here), and safety. The trial is registered with ClinicalTrials.gov, NCT046 02013. Enrolment is completed and follow-up is ongoing. Results: Between Oct 19, 2020, and Dec 08, 2023, 52 patients were enrolled. The median age was 65 years (IQR 58-71), 11 (21.1%) of 52 patients had stage IVA disease, and 49 (94.2%) patients were male and 3 (5.8%) were female. 50 (96.2%) of 52 patients patients completed the planned chemoradiotherapy. After a median follow-up of 15.0 months (IQR 7·9-28·0), the median PFS was not reached. The 1-, 2- and 3-year OS rates were 93.7%, 84.0% and 45.0%, respectively.The most common grade 3 or worse adverse event was neutropenia (23 [44.2%] of 52). Eight (15.4%) had treatment-related pneumonitis, but no patient died. Conclusions: Combining toripalimab with definitive chemoradiotherapy provided encouraging activity and acceptable toxicity in patients with locally advanced oesophageal squamous cell carcinoma, and this regimen warrants further investigation. Clinical trial information: NCT04602013 .
Prevalence and outcomes of acute kidney injury among hospitalized patients with gastric cancer: Insights from a National Inpatient Sample study (2018-2020).
Authors: Rabia Iqbal, Mrunanjali Gaddam, Ahmad Taimoor Bajwa, Jayalekshmi Jayakumar, Manasa Ginjupalli, Vikash Kumar, Dhairya Nanavaty, Ana Colon Ramos, Jincy Clement
Journal: Journal of Clinical Oncology (2024)

e16124 Background: Acute kidney injury (AKI) occurs in 50-60% of the patients admitted to the hospitals, and up to almost 20% of those patients have underlying cancer. AKI has been associated with high mortality and adverse outcomes in cancer patients. This relationship between cancer and kidney health, known as "the kidney-cancer connection has attracted considerable interest in research circles. In this study, we aimed to evaluate the outcome of AKI in hospitalized patients with gastric cancer. Methods: A retrospective analysis was conducted using the National Inpatient Sample database from 2018 to 2020 and the ICD- 10 codes to identify the patients &gt; 18 years old with the principal diagnosis of Gastric Cancer. We evaluated the effect of acute kidney injury (AKI) on mortality, morbidity outcomes, and resource usage in patients with gastric cancer. Categorical variables underwent comparison using the chi-square test, while continuous variables were compared using the t-test. Multivariate analysis was conducted to derive the odds ratio, and all weighted analyses were carried out using STATA. Results: We identified a total of 123,935 patients with a primary diagnosis of gastric cancer who were hospitalized between 2018 and 2020 in the United States. Out of them, 20% (24,787) of the patients had developed acute kidney injury during the hospital admission. The mean age of the patients was 69 years. Of these patients, 67% were male, and the remaining 33% were female. The mortality for gastric cancer patients with AKI was 18.3%, while it was 4.7% for patients without AKI. After adjusting for confounders, AKI had higher odds of mortality (Adjusted odds ratio [aOR] for mortality 4.41, 95% confidence interval [CI]: 3.96-4.91, P &lt; 0.001). AKI was also associated with higher resource utilization, including a higher length of stay (LOS) (mean LOS increased by 9.5 days vs 6.5 days in patients without AKI) and higher hospital charges (by $127,814). Conclusions: Our study concludes that the patients with gastric cancer who developed Acute Kidney Injury during the hospital stay had worse outcomes. Identifying AKI early on can help with timely intervention, which can reduce adverse outcomes. Thus it is extremely important for nephrologists and oncologists to closely monitor patients' renal function throughout their treatment.[Table: see text]
Analysis of transition metals in glioblastoma tumor and plasma samples.
Authors: Ganesh Shenoy, Madison Kuhn, Aurosman Sahu, Vladimir Khristov, Madison Heebner, Hannah E. Wilding, Taylor Clegg, Debarati Bhanja, Quinn Wade, Laura J. Liermann, Dongxiang Wang, Nataliya Smith, Chachrit Khunsriraksakul, Kondaiah Palsa, Becky Slagle-Webb, Alireza Mansouri, Brad Zacharia, Elizabeth Proctor, James Connor
Journal: Journal of Clinical Oncology (2024)

e14029 Background: Transition metals such as copper, iron, zinc, and manganese are known to play essential roles in human physiology as evidenced in conditions where these metals are dysregulated. The role of transition metals in glioblastoma biology has been largely understudied. Here we investigated whether plasma and tumor transition metal content is associated with glioblastoma patient outcomes. Methods: Transition metal content was measured in 31 glioblastoma tumor samples, 21 of which had matched plasma samples, using inductively coupled plasma mass spectroscopy (ICP-MS) or inductively coupled plasma atomic emission spectroscopy (ICP-AES). Concentrations of transition metals in plasma and tumor were then then correlated with clinical parameters including median overall survival (mOS) as well as plasma cytokines. Results: Spearman correlation analysis of transition metals in glioblastoma tumor samples found that tumor manganese and tumor zinc (R = 0.52, p = 0.0048) as well as tumor copper and tumor zinc (R = 0.36, p = 0.038) were positively correlated. Plasma transition metal content did not correlate with tumor transition metal content. Kaplan-Meier and Cox regression survival analysis between high and low expressors of each respective transition metal, separated at the median, revealed that high plasma iron content was associated with prolonged survival (median overall survival: 30.1 vs 12.4 months, P = 0.0036). Plasma from glioblastoma patients in the high plasma iron group had increased levels of IFN-β (10.91 pg/mL vs 7.43 pg/mL, P = 0.004). Plasma or tumor concentrations of copper, zinc, or manganese did not associate with survival. Conclusions: Increased plasma iron content is associated with prolonged survival as well as increased plasma IFN-β levels, suggesting a possible link between iron and immune responses in glioblastoma patients.
Analysis of ctDNA assay as a strategy for watchful waiting in locally advanced esophageal cancer.
Authors: Hao Q. Q To, Harry Menon, Garrett Barnard Green
Journal: Journal of Clinical Oncology (2024)

e16126 Background: Standard treatment for locally advanced esophagogastric (EG) cancer is neoadjuvant chemoradiotherapy (CRT) followed by surgery. The treatment goal is curative in order to control the tumor in the thorax, prevent regional recurrence, and to help prevent or delay metastatic progression. Despite achieving pathologic complete response (pCR) after surgery, patients with supposed local control may have recurrence up to a third of the time. Circulating tumor DNA (ctDNA) is an evolving tool in the field of oncology used as an informative biomarker. We provide longitudinal, real world observation of ctDNA minimal residual disease (MRD) to predict pCR and risk of recurrence. Methods: 22 participants with newly diagnosed locoregional EG cancer were enrolled under single institution approved protocol [IRB#1864127-7]. CtDNA-based MRD levels were obtained by Natera SignateraTM bespoke mPCR-NGS assay. Additionally, Natera Altera TM was used as a non-invasive biopsy to provide the comprehensive tumor-specific genomic profile. We evaluated thirteen participants who underwent definitive surgery and those who did not. Non-invasive plasma samples were surveilled at various timepoints which included the time of diagnosis, during neoadjuvant CRT, after definitive surgery. The primary outcome is a comparison of assay recurrence (AR) to disease recurrence (DR) defined as radiologic or clinical disease recurrence in participants with locoregional disease. Exploratory endpoints examine the profile of tumor. Results: Baseline levels were detected (n = 22) at new diagnoses. Longitudinal results demonstrated ctDNA clearance in eight participants while undergoing neoadjuvant chemoradiaton. Residual ctDNA were found in five participants for which two had clinical disease recurrence. Esophagectomy was done in three participants achieving pCR. Post procedural ctDNA were detected in one participant. Conclusions: The clearance of ctDNA favors less clinical disease recurrence in this study. This may indicate that ctDNA clearance confers lower risk of relapase. However, a larger cohort prospective study will be needed to validate the application of ctDNA as an early biomarker. The future application of ctDNA can be used to identify patients who may benefit from a watchful waiting adjuvant strategy instead of proceeding with invasive esophagectomy.
Personalized neoantigen-pulsed autologous dendritic cells vaccine as an adjuvant treatment for patients with newly-diagnosed glioblastoma multiforme: A phase I trial.
Authors: Yang Zhang, Xiaohan Chi, Xudong Cheng, Yu Zhang, Kangna Zhang, Na Huang, Nan Ji
Journal: Journal of Clinical Oncology (2024)

e14025 Background: Glioblastoma Multiforme (GBM) is the most common and aggressive primary brain malignancy in adults. We herein report a phase I trial using personalized neoantigen-pulsed autologous dendritic cells (nDC) vaccine as an adjuvant treatment for patients with newly-diagnosed GBM. Methods: It is a single-center, single-arm phase I trial, enrolling patients aged 18-75 years old, with newly-diagnosed GBM and tumor resection extent ≥90%. Tumor specimens were sequenced for identification of personalized neoantigens. A total of 3-10 neoantigen peptides were loaded into DC to generate the nDC vaccine. The vaccine was administered subcutaneously for 5-6 doses at 1×10^7 cells following concomitant radiotherapy plus temozolomide. The primary objective is safety. Secondary objectives include survival outcomes and T cell immune response against the neoantigens. Results: As of Dec. 31, 2023, eleven patients completed at least one dose of vaccination and were included in the safety analysis; eight patients completed planned doses and were included in the efficacy analysis. All the patients reported Treatment-emergent adverse events (TEAEs). Most TEAEs were grade 1 or 2. One patient reported two grade 3 TEAEs: decreased white blood cell count and decreased lymphocyte count. Pyrexia was considered as treatment-related adverse event (TRAE) that was reported in two (18.2%) patients. No treatment-related deaths occurred. Among eight efficacy-assessable patients, seven (87.5%) patients kept progression-free for at least 5.4-27.3 months; one patient progressed at 10.2 months after surgery and achieved complete remission after receiving anti-PD1 plus bevacizumab therapy; compared to the baseline level, a median 15-fold (3 to 506-fold) increase of neoantigen-specific cytotoxic T cells was detected in their peripheral blood samples post-vaccination, indicating strong anti-tumor T cell responses elicited by the nDC vaccine. Conclusions: The nDC vaccine, combined with the standard treatments for GBM, was well tolerated. Initial results from this ongoing study have exhibited encouraging survival outcome of the nDC vaccine for patients with newly-diagnosed GBMs. Clinical trial information: NCT04968366 . [Table: see text]
Breaking barriers: Real-world data on immunotherapy in non-small cell lung cancer with large brain metastases.
Authors: Narayanan Sadagopan, Edina Komlodi-Pasztor, Irina Veytsman
Journal: Journal of Clinical Oncology (2024)

e14002 Background: Non-small cell lung cancer (NSCLC) patients with large brain metastases (BrM) defined as &gt; 2 cm historically face grim prognoses. Immunotherapy, emerging as a state-of-the-art treatment in NSCLC treatment, has not been extensively studied in the context of large BrM. The use of immunotherapy in these patients is complicated by factors such as steroids use and local interventions like surgery and/or radiation treatment. Methods: We conducted a retrospective study across three MedStar Georgetown Cancer Network sites to evaluate outcomes in NSCLC patients with large BrM. Inclusion criteria comprised of patients aged 18 years or older with NSCLC diagnosed between 01/01/17 to 12/31/2022 who started immunotherapy after the diagnosis of at least one BrM 2 cm or more in diameter. Intracranial progression free survival (PFS), overall survival (OS), and relevant clinical factors were analyzed. Steroid use was not included due to documentation limitations. Cox penalized regression was used to assess PFS and OS while power analysis was not done due to the sample size. Results: The study included 36 patients all of whom underwent neurosurgery and/or radiation before starting immunotherapy. Median follow up duration was 17.6 months. The population was 58.3% female, median age 64.4 years, 77.8% lung adenocarcinoma, 91.7% received pembrolizumab for immunotherapy, and median duration of immunotherapy was 178 days. Median intracranial PFS was 9.2 months and median OS reached 31 months. The hazard ratio (HR) was 0.07 (95% confidence interval (CI) 0.02-0.26) for intracranial PFS in patients who received at least 90 days of immunotherapy compared to those who received less than 90 days of immunotherapy. Each additional 30 days of immunotherapy was associated with an OS HR 0.77 (95% CI 0.67-0.90). Higher PD-L1 status was not associated with improved outcomes. Conclusions: The study highlights the potential of immunotherapy as a valuable treatment for NSCLC patients with large BrM, a population often excluded from clinical trials. In our retrospective analysis, extended immunotherapy demonstrated positive impacts on both intracranial PFS and OS. Future directions should focus on prospective evaluation of the optimal timing of immunotherapy relative to upfront large BrM treatment, with a specific emphasis on understanding the role of steroids dosing in this context.
Developing behavioral intervention to support molecular testing of patients with biliary tract cancer.
Authors: Garrett Bowman, Mahmoud Ouf, Lin Zhu, Heather Derry-Vick, Chiranjeev Dash, Judy Huei-yu Wang, Monika Kulasekaran, James O'Bryan, Christopher Loffredo, Aiwu Ruth He
Journal: Journal of Clinical Oncology (2024)

TPS1641 Background: Biliary tract cancer (BTC) represents 7% of gastrointestinal malignancies in the United States, with an incidence of 0.5 to 2.0 cases per 100,000 individuals. Standard care involves systemic chemotherapy, predominantly gemcitabine and cisplatin. Recent advancements in immunotherapy, as evidenced by the TOPAZ-1 trial and KN966, support the use of durvalumab, and pembrolizumab as treatment options. Genetic tumor testing identifies up to 40% of BTC patients with targetable mutations, leading to recent FDA approvals for FGFR2 inhibitors - pemigatinib, infigratinib, futibatinib, and IDH1 inhibitor ivosidenib. The emerging data on inhibitors targeting the BRAF mutation, together with HER2 amplification, underscore the importance of understanding the tumor's molecular profile. Navigating this evolving treatment landscape emphasizes an unmet need for patients to comprehend the pivotal significance of tumor molecular profiling in formulating effective and personalized treatment plans. Identifying knowledge gaps among BTC patients concerning tumor genetic testing and precision medicine, along with strategies to address these gaps, holds promise for improving the management and the outcome of patients with BTC. Methods: This is a behavioral intervention study where participants will undergo two in-person survey interviews before and after an educational intervention. The initial survey aims to establish baseline knowledge about the BTC diagnosis and treatment and ascertain preferences for various educational interventions. Patients’ knowledge gap will be determined by comparing their responses to the initial survey and medical history documented by their treating physicians. They will then be provided with a 10-minute educational video. Participants will have the flexibility to access the video multiple times. Within 6 weeks from enrollment, they will have a post-education survey to determine the effectiveness of the education intervention. Following completion of baseline surveys, collaboration with key stakeholders including medical oncology and community perspectives will be initiated to identify knowledge gaps and inform the design of an educational intervention. The study enrollment will be targeted at BTC patients receiving systemic therapy at Georgetown University Hospital, Fox Chase Cancer Center, and Hackensack Meridian Health. Ten participants are enrolled and have completed the first survey and intervention. This study is currently enrolling participants: GUIRB: STUDY00007119.
Incidence of venous thromboembolism in newly diagnosed glioblastoma multiforme and associated risk factors: A retrospective chart review.
Authors: Nasser Al Majarafi, Duaa Omar Binjabal, Gregory Russell Pond, Hal W. Hirte
Journal: Journal of Clinical Oncology (2024)

e14040 Background: Patients diagnosed with glioblastoma multiforme (GBM) are recognized as a population at high risk of developing venous thromboembolism (VTE) (1,2). A retrospective chart review of patients diagnosed with GBM at the Juravinski Cancer Centre (JCC) was performed with the primary objective to assess the incidence of the development of VTE in newly diagnosed GBM. The secondary objective was to identify patients who were at higher risk and who could benefit from prophylactic anticoagulation. Methods: This was a single-centre, retrospective cohort study. We reviewed the charts of 528 patients diagnosed with GBM at the JCC from an 8-year period from January 1, 2013 to December 31, 2020. Information on the following factors was collected: Body-mass index (BMI), comorbidities (hypertension, diabetes, dyslipidemia, smoking history), performance status, location and size of tumour, degree of resection, presence of and location of weakness, baseline blood counts, treatments administered, date of diagnosis and time to death or last follow-up. Results: Over the period of review, a total of 528 patients were identified. 111 patients (21%) were diagnosed with VTE. The location of VTE was as follows: 39 patients (35%) unilateral lower extremity deep venous thrombosis (DVT), 8 (7%) unilateral upper extremity DVT, 8 (7%) bilateral lower extremity DVT, 30 (27%) pulmonary embolism (PE), and 25 (23%) DVT and PE. Most VTE (87%) occurred within 12 months of diagnosis of GBM. On univariate and multivariate analysis, no factors were identified that contributed to an increased risk of VTE. Conclusions: Newly diagnosed patients with GBM have been shown to have a significant risk of developing VTE. The AVERT study (3) demonstrated the preventive benefit of administering a direct oral anticoagulant (DOAC) to cancer patients, including those with GBM, at high risk of developing VTE (3). Thus consideration should be given to treating patients with GBM with a DOAC at the time of diagnosis. The benefit of preventive treatment will need to be balanced against the risk of bleeding in these patients. References: 1. Marras LC et al. Cancer 2000; 89(3):640–6; 2. Lim G et al. Cureus 2018;10(5): e2678; 3. Carrier M et al. N Engl J Med 2019; 380:711-9.