tbuckley/cabot-search huggingface dataset:
Real-world adoption of 3 months of adjuvant oxaliplatin chemotherapy in patients with stage III colorectal cancer (CRC).
Authors: Tharani Krishnan, Joao Paulo Solar Vasconcelos, Howard J Lim, Jonathan M. Loree, Janine Marie Davies, Karamjit Gill, Sharlene Gill
Journal: Journal of Clinical Oncology (2024)

83 Background: Based on the IDEA analysis, 3 months (mos) of adjuvant chemotherapy (ACT) with CAPOX has emerged as an option for both low-risk and high-risk stage III CRC. This has resource utilization, cost and toxicity benefits (particularly less neurotoxicity) without compromising efficacy. This study examines the patterns of uptake of CAPOX vs FOLFOX and duration of ACT in a contemporary post-COVID real-world cohort of patients (pts) in the province of British Columbia (BC), Canada. Methods: The provincial pharmacy database was used to identify pts with resected stage III CRC who received adjuvant CAPOX or FOLFOX between January 2021 and December 2022. Pts with rectal cancer requiring neoadjuvant chemotherapy or radiotherapy were excluded. Demographic, tumor, and treatment information was collected. “High-risk features” were defined as pT4 or pN2 tumors. “Urban” setting was defined based on the population size of the regional health authority. Descriptive statistical analyses were performed to examine baseline characteristics and Fisher’s exact test was used to examine univariate associations. Results: 452 pts were included, of which 234 (52%) and 218 (48%) were planned to receive 3 and 6 mos of ACT respectively (see table). Within the 3 mos group, 226 (97%) received CAPOX. Within the 6 mos group, there was a 51%/49% split between CAPOX/FOLFOX. By univariate analysis, factors associated with 3 mos of CAPOX vs 6 mos of ACT were age &gt;70y (P=0.039), low/intermediate grade (P=0.005) and low-risk stage III disease (P&lt;0.0001). 29% of pts planned for 6 mos of oxaliplatin ACT had low-risk disease, with 52% of these receiving CAPOX. Conclusions: 3 mos of adjuvant CAPOX is an accepted option for nearly all pts with stage III disease with consequent less neurotoxicity and fewer treatment visits. Yet, in this contemporary cohort, use of 3 mos of adjuvant CAPOX remains low and is associated with older age and low-risk disease. 6 mos of oxaliplatin is still being offered to pts with low-risk disease. Exploration of patient preferences, real-world treatment and time toxicities, and resource costs may improve more widespread adoption of 3 mos of adjuvant CAPOX in stage III CRC. [Table: see text]
Safety and efficacy of external beam radiotherapy in hepatocellular carcinoma patients previously treated with yttrium-90 radioembolization.
Authors: Kanokphorn Thonglert, Joseph Tsai, August C Anderson, Matthew J. Nyflot, Stephen R. Bowen, Clemens Grassberger, Peter Zaki, Yulun He, Guy E. Johnson, Wayne L Monsky, Smith Apisarnthanarax
Journal: Journal of Clinical Oncology (2024)

523 Background: Data on the safety and efficacy of external beam radiation (EBRT) after Yttrium-90 (Y-90) radioembolization for hepatocellular carcinoma (HCC) is limited. We report our experience using EBRT to treat HCC patients who were previously treated with Y-90. Methods: We analyzed 31 HCC patients who received EBRT following Y-90 treatment. Eighteen were treated with photon therapy (40-50 Gy in 5 fractions), and thirteen with proton therapy (42-67.5 Gy in 15 fractions). Twenty-four patients underwent Y-90 segmentectomies, while seven received Y-90 lobar treatment. The median administered Y-90 activity was 44.4 mCi (range 8.3-114.4). Results: Patients had received 1 (n=14), 2 (n=7), or ≥3 (n=10) prior Y-90 treatments. EBRT was administered for various reasons: poor Y-90 response in two patients, technical limitations in 25 patients, and other reasons in four patients. Ten patients had previously received Y-90 within the EBRT area, thirteen outside the EBRT area, and eight in both regions. The median tumor size was 3.8 cm (range 1.6-19.4). Twenty-seven patients had Child-Pugh (CP)-A score, three had CP-B, and one had CP-C baseline liver function. With a median follow-up of 21 months, the 2-year progression-free survival, and overall survival rates were 28%, and 43%, respectively. The 2-year cumulative incidence of local failure was 7%. CP+2 progression was observed in five patients (16%): three had Y-90 delivered outside the EBRT area and two within the EBRT area. Three patients had possible RILD-related deaths. Grade 3+ biliary complications occurred in three patients (10%): one biloma, one liver abscess, and one biliary stricture which resulted in a possible treatment-related death. All three patients had received at least two prior Y-90 treatment overlapping with the area treated with EBRT and had tumors located near the porta hepatis. Conclusions: EBRT for HCC patients previously treated with Y-90 is feasible and offers excellent local control. Hepatic function and biliary toxicities are potential complications and should be weighed against the clinical benefits.
The role of pre-operative ctDNA in resectable intrahepatic cholangiocarcinoma.
Authors: Woo Jin Choi, Zhihao Li, Christian Magyar, Antony Tin, Erik Spickard, Himanshu Sethi, Minetta C. Liu, Roxana Bucur, Robert C Grant, Arndt Vogel, Jennifer J. Knox, Geoffrey Liu, Steven Gallinger, Gonzalo Sapisochin, Grainne M. O'Kane
Journal: Journal of Clinical Oncology (2024)

528 Background: Genomic profiling of circulating tumor DNA (ctDNA) is increasingly used in intrahepatic cholangiocarcinoma (iCCA) to inform precision oncology approaches and determine resistance mechanisms to targeted therapies. The application of pre-operative ctDNA testing in the management of iCCA for prognostication remains unclear. Methods: In this retrospective study, we analyzed pre-operative plasma samples from 14 patients who underwent curative resection for iCCA without neoadjuvant therapy. A personalized and tumor-informed assay (Signatera; Natera, Inc.) was used for the detection and quantification of ctDNA. We correlated ctDNA profiles with baseline tumour characteristics and clinical outcomes. Results: The mean interval between pre-operative blood collection and surgery was 43 days (range: 1 to 90 days). ctDNA was detected in all patients except for one with stage Ia (AJCC 8th) disease (Table). The mean pre-operative ctDNA concentration was lowest in the stage Ia group [4.2 mean tumor molecules (MTM)/mL] and highest in the stage II group (134.0 MTM/mL). The mean pre-operative ctDNA concentration did not exhibit a linear correlation with disease recurrence or mortality rates, however, it showed a moderate-to-good linear correlation with the largest pathologic tumor size (R 2 = 0.55). Among the three patients who had IDH1/2 mutations tracked in the plasma by Signatera, two patients had positive IDH1/2 detection in ctDNA with mean ctDNA concentrations of 83.7 MTM/mL (range: 33.8 to 133.5 MTM/mL). The patient with the second-highest ctDNA concentration (133.5 MTM/mL and 1818 days follow-up) had stage Ib disease with an IDH1 mutation but has shown no evidence of recurrence. Conclusions: In the pre-operative setting for iCCA resections, ctDNA can be reliably detected across all disease stages using a tumor-informed approach, even when blood is collected up to 90 days before surgery. While single time-point pre-operative ctDNA concentration levels do not appear to correlate with outcomes, similar to previous reports in colon adenocarcinoma, they may correlate with tumor volume. Further studies are needed to evaluate the utility of tumor-informed ctDNA testing in the post-operative setting to detect molecular residual disease for improved prognostication. [Table: see text]
COLONTOWN Searching Safari: Education to remove barriers to pursue clinical trials for patients with metastatic colorectal cancer (mCRC).
Authors: Julie Clauer, Nancy Seybold, Manju George
Journal: Journal of Clinical Oncology (2024)

82 Background: Clinical trials can expand otherwise limited treatment options for patients with metastatic cancer. Yet, the complexity of the trial landscape can prevent patients from pursuing trials. Even in mCRC patients motivated to participate in trials, 79% described trial search negatively, mainly ‘overwhelming.’ We hypothesized that “clinical trial-literacy” and familiarity with the tools/process of pursuing trials were critical precursors for patients to incorporate trials into their treatment plan. To test this, we, as managers of COLONTOWN, a large, online CRC patient/caregiver community, developed an interactive course. Methods: We reviewed many posts from the COLONTOWN clinical trial groups to identify gaps between the desire to participate in a trial and the knowledge/tools needed to do so. We then determined those most likely to benefit as mCRC MSS patients interested in, but not in urgent need of, trials. We developed a 4-week long course with 5 hours of live online sessions and 5 hours of homework. Participants built fluency in the language of clinical trials, learned about available tools, and identified and assessed trials in the context of their personal needs and disease dynamics. Unlike most other trial resources, the focus was on informed patient-centered decision-making, not on the science or mechanics of trials. The course was offered 3 times in 2022/23 with iterative improvements after each session. Participants (n=48) were assessed for their attitudes around trials before and after the course to measure impact. Results: We found that our repeatable, scalable course improves mCRC patient perceptions of and skills to pursue trials as evidenced by pre-course vs. post-course surveys. This included average response to “How prepared do you feel to find a clinical trial?” increasing from 2.1 to 3.8 on a 5-pt scale and positive sentiment about the process rising from 7% to 71% (table). Positive feedback on meeting course objectives and amount of coursework being ‘just right’ (96% and 92% of responses, respectively) support the material’s value for time invested. Conclusions: Through systematic skill building, self reflection, and practical tools, our guided course can build confidence and empower patients and caregivers to take the next step to pursue clinical trials. Patient education can indeed help overcome often-overlooked emotional and knowledge barriers to pursuing clinical trials present even in a motivated patient population. Next, we plan to create and assess the benefit of an additional on-demand e-learning course and to expand to other patient groups. [Table: see text]
Stereotactic radiotherapy plus anti PD-1 therapy in patients with locally advanced unresectable pancreatic cancer: Results from a phase 1/2 clinical trial (CA209-9KH).
Authors: Milan Vosmik, John Stanislav, Josef Dvorak, Beatrice Mohelníková-Duchoňová, Bohuslav Melichar, Radka Lohynska, Aleš Ryška, Johana Krempova, Igor Sirak
Journal: Journal of Clinical Oncology (2024)

649 Background: The outcomes after the treatment for pancreatic ductal adenocarcinoma (PDAC) are generally disappointing. Except for MSI high tumors, PDAC is considered to be resistant to immune checkpoint inhibitors (ICI). Radiotherapy is thought to be a potential option to foster the effect of ICI. This investigator-initiated trial evaluated safety and efficacy of combining stereotactic radiotherapy (SRT) and ICI. Methods: In this open-label, multicenter phase 1/2 study, patients (pts) aged ≥ 18 years with histologically confirmed locally advanced unresectable PDAC with no distant metastases were enrolled after initial four cycles of induction chemotherapy with FOLFIRINOX. The experimental treatment consisted of SRT (32 Gy in 4 fractions/4 weeks) and sequential nivolumab (N) therapy (3mg/kg every two weeks) administered until disease progression or unacceptable toxicity. After N discontinuation pts could continue treatment with standard chemotherapy regimens. The primary end point was safety (events graded according to NCI CTCAE 4.03 criteria). The secondary objectives were progression free survival (PFS), overall survival (OS), evaluation of selected biomarkers, and quality of life (QoL; EORTC QLQ-C30 questionnaire). The PFS and OS were defined as the time from enrollment to event (i.e., did not include 3-month of ICT and screening). Results: A total of 22 pts. were screened, and 15 pts. were enrolled. Median age was 58 (range 38-74) years, and 53 % were males. All tumors were microsatellite (MS) stable or had unknown MS status. All patients underwent SRT according to the study protocol and all started N. The median number of N cycles was 11 (range 2-17). The toxicity of SRT was low and non-significant. The toxicity of N therapy was expectable. No Grade 4-5 toxicity was observed. Three pts. discontinued therapy because of toxicity (liver test elevation in two cases and unmanageable arthralgia). Median PFS and OS were 8.1 and 13.0 months, resp.; 12-month PFS and OS were 0 % and 66.7%, resp.; and 24-month OS was 8.9 %. The level of selected biomarkers correlated with clinical or radiological disease control. The QoL assessed by pts during the therapy was acceptable, deterioration of QoL in most cases occurred with tumor progression. Conclusions: The toxicity of SRT and N therapy was low and acceptable. There was no unexpected toxicity of combination of SRT of PDAC primary tumor and N, but this regimen did not lead to any long-term treatment responses. Trial registration: EudraCT: 2017-003404-52; ClinicalTrials.gov: NCT04098432. The study was financially supported by Bristol-Meyer-Squibb. Clinical trial information: NCT04098432 .
Number of subsequent treatments and time to recurrence in hepatocellular carcinoma.
Authors: Juan Jose Juarez, Vaibhav Birda, Santiago Sucre, Esteban Garita, Kevin Pacheco-Barrios, Rodrigo Paredes, Andrea J. Bullock, Ammar Sarwar, Mary Linton Bounetheau Peters
Journal: Journal of Clinical Oncology (2024)

526 Background: Hepatocellular carcinoma (HCC) is often managed with locoregional therapies including surgical resection, ablation, transcatheter arterial chemoembolization (TACE), and selective internal radiation therapy (Y90). Most patients require multiple treatments over several years due to ongoing development of new lesions, distinct from other cancer types. Our project aims to analyze this treatment trajectory and the impact of treatment selection. Here we present an interim analysis focusing on the number of subsequent therapies and time to first recurrence (TTR). Methods: We identified 202 patients newly diagnosed with HCC between 2019-2021 who were seen in the BIDMC Liver Tumor Multidisciplinary Clinic. Complete abstraction of medical records was performed in 51 patients to date. Our primary outcome was of the number of subsequent therapies depending on the selected first-line locoregional therapy. Incidence risk ratios (IRR) were obtained via a crude and adjusted (age, gender, race, Child Pugh) linear regression model. Ablation was used as the reference treatment. Secondary outcomes included survival analysis of TTR, overall survival (OS) and time to initiation of systemic therapy. TTR was defined as the appearance of new lesions, excluding residual disease. Results: Mean age at diagnosis was 65 years old, 73% were male, and 92% ECOG 0. 37 patients out of 50 had recurrence, almost all local (97%). The total number of subsequent therapies received was 110; the most common treatment received on first recurrence was ablation (59%) followed by Y90 (24%). Patients who received TACE were more likely to undergo a higher number of subsequent therapies in both the unadjusted (IRR 2.51, p&lt;0.001, 95%CI 1.6-3.9) and adjusted analysis (IRR 4.43 p&lt;0.001, 95%CI 2.5-8.1) with 4.4 (2-9) mean subsequent treatments when compared to ablation with a mean number of subsequent treatments of 1.47 (0-7). Y90 had 1.85 (0-7) mean subsequent treatments and surgery 1.87 (0-7), with inconclusive results regarding IRR when compared to ablation. Median TTR was 19.1 months (10.2-29.3) with ablation having the longest time with 22.2 months (13.2-31.1), followed by surgery with 20.3 months (13.3-29.3), Y90 with 19.1 months (6-NR) and TACE with 12.1 (6.1-21.2). Median OS was not reached, and only 5 patients started systemic therapy. Conclusions: This interim analysis shows that patients treated with TACE as the first locoregional therapy are likely to undergo a higher number of subsequent treatments when compared to ablation.
The impact of a pancreatic cancer multi-disciplinary clinic on patient-centric outcomes.
Authors: Connor Hannon, Patrick L. Quinn, Stephanie Iacono, Rachel Konik, Angela Sarna, Gennaro Di Tosto, Krista Maxey-Kohn, Jordan M. Cloyd, Timothy M. Pawlik, Adrei Manilchuck, Anne M. Noonan, Arjun Mittra, Shafia Rahman, Pannaga G. Malalur, Mary Dillhoff, Ashish Manne, Aslam Ejaz
Journal: Journal of Clinical Oncology (2024)

641 Background: A one-day multi-disciplinary clinic allows for a comprehensive evaluation of patients in a single-visit format. This study aims to evaluate the impact of a one-day pancreatic cancer multi-disciplinary clinic (PMDC) on patient-centric outcomes. Methods: Patients with pancreatic cancer who were seen at The Ohio State University PMDC from January 2021 to March 2023 were identified. Patient-centric outcomes were evaluated including time from diagnosis to first evaluation and treatment, number of supportive care referrals completed, and number of physical trips to the medical center leading up to the first treatment. Outcomes were compared to pancreatic cancer patients seen in the year prior to the opening of the PMDC (non-PMDC). Results: Among the 139 PMDC and 141 non-PMDC patients, the median number of days between referral and treatment initiation was similar (PMDC: 33 days (IQR: 22, 44) vs. non-PMDC: 32 days (IQR: 23, 42); p &gt;0.9). The median time between diagnosis and treatment initiation was also similar (PMDC: 28 days (IQR: 19, 37) vs. non-PMDC: 30 days (IQR: 21, 37); p=0.4). Of note, PMDC patients received more supportive care visits within 30 days of diagnosis (PMDC: 2 (IQR: 1, 2) vs. non-PMDC: 0 (IQR: 0, 1) ; p &lt;0.001) and completed more visits with cancer providers (PMDC: 7 (IQR: 6, 8) vs. non-PMDC: 5 (IQR: 4, 7); p &lt;0.001) compared with non-PMDC patients. In addition, PMDC patients also required fewer physical trips to the medical center (PMDC: 4 (IQR: 3, 5) vs. non-PMDC: 4 (IQR: 3, 6); p &lt;0.001). Conclusions: Pancreatic cancer patients seen in a one-day multi-disciplinary clinic attend a greater number of coordinated appointments and receive more supportive care services with fewer physical trips to the medical center compared with patients not seen in a PMDC clinic. Future studies should focus on the long-term patient-centric benefits of a multi-disciplinary approach for cancer patients.
Evaluation of a real-world clinico-genomics database of patients with upper gastrointestinal (GI) malignancies in Japan.
Authors: Senaka A. Peter, James R. Rogers, Xinyue Liu, Cai Chen
Journal: Journal of Clinical Oncology (2024)

400 Background: The genomic profile of gastrointestinal (GI) cancers provides essential information for precision medicine, however, there is limited availability of real-world data in Asian populations as they are not well-represented in most publicly accessible clinico-genomic databases. In this retrospective study, we evaluated the clinical and genomic characteristics of upper GI cancer patients in the database from an academia-industry collaborative nationwide cancer genome screening project in Japan. Methods: The Screening Projectfor Individualized Medicine in Japan (J-SCRUM) GI-SCREEN enrolled advanced GI cancer patients from 26 sites before planned or during systemic therapy from 2015 to 2019. Archived formalin-fixed paraffin-embedded tumor tissue was analyzed by next-generation sequencing (NGS) using Oncomine Cancer Research Panel and Oncomine Comprehensive Assay. Patients with gastric (GC), esophageal (EC) and pancreatic (PC) cancers were identified in the database. The frequency of key actionable genomic alterations in each cancer cohort was explored and compared to similar upper GI cohorts in The Cancer Genome Atlas (TCGA), a publicly available genomics database initiated in 2005 and concluded sample collection in 2013 with most samples from White cancer patients. Results: A total of 872 GC (mean age at registration [SD]: 64y [12]; percent males: 65%), 265 EC (64y [9]; 78%) and 495 PC (64y [10]; 60%) patients were identified. The majority (&gt;70%) of samples were obtained from primary sites. Adenocarcinoma was the most common histological type for GC (85%) ad PC (76%), while squamous cell (76%) was the most common among EC patients. In the GC cohort, the prevalence of key actionable genomic alterations in J-SCRUM GI-SCREEN vs TCGA (N = 380) was, TP53 mutation (49% vs 49%), ERBB2 amplification (14% vs 13%), PIK3CA mutation (11% vs 14%), MYC amplification (9% vs 12%) and MET amplification (2% vs 3%). In the EC cohort, the prevalence in J-SCRUM vs TCGA (N = 182) was TP53 mutation (77% vs 87%), NFE2L2 mutation (21% vs 10%), PIK3CA mutation (9% vs 9%) and CDKN2A mutation (8% vs 8%). In the PC cohort, the prevalence in J-SCRUM vs TCGA (N = 150) was KRAS hotspot mutation (90% vs 93%), KRAS G12D (43% vs 41%), KRAS G12V (32% vs27%), TP53 mutation (58% vs 64%), BRCA1/2 deleterious mutation (5% vs 5%), ATM deleterious mutation (6% vs 5%) and MYC amplification (5% vs 5%). Conclusions: As part of a nationwide cancer genome screening project, J-SCRUM GI SCREEN database provides comprehensive genomic information for Asian population (Japan). The prevalence of key actionable gene alterations in each tumor type was highly comparable between J-SCRUM GI-SCREEN and TCGA data.