tbuckley/cabot-search huggingface dataset:
Pancreatic biopsy evaluation with nsCanary: A “smart ROSE” device for feedback on sample adequacy and cancer presence in endoscopic biopsies—Initial human clinical trial results.
Authors: Les Bogdanowicz, Onur Fidaner, Martina Guidetti, Federica Dibennardo, Daniel Gehrke, Donato Ceres, Margaret John, Constantine Bovalis, Isaac Raijman
Journal: Journal of Clinical Oncology (2024)

618 Background: Pancreatic cancer (PC) accounts for 0.5 million new cases and 4.7% of the world's cancer-related deaths in 2020. Endoscopic ultrasound (EUS) guided fine needle biopsies (FNB) are the current standard of care for confirming suspicious lesions, however the diagnostic accuracy is reported below 70%. Rapid on-site evaluation (ROSE) improves the diagnostic performances of biopsies to reduce the number of needle passes, complication rates, and the need for additional procedures. However, availability of an on-site pathologist is often not feasible. NovaScan has pioneered the use of an impedance spectroscopy biomarker for cancer detection in different tissues based on the Cole Relaxation Frequency (CRF). NovaScan has developed the nsCanary, a ”smart ROSE” device that assesses PC presence in FNBs obtained during endoscopic procedures ex vivo, in real-time and on-site, without altering the tissue sample or affecting the workflow. Methods: Data were collected in a double-blind, IRB approved study from a cohort of 53 patients (28 males, 25 females) undergoing EUS procedures for suspected pancreatic lesions at the Texas International Endoscopy Center. FNBs were performed with a 22 gauge biopsy from a transduodenal approach. Each biopsy sample was transferred onto a disposable strainer allowing for any excess fluid to drain. An electrode for scanning was placed onto the core samples for data collection with the nsCanary a low cost, portable device used in the operating room. CRF is measured in the 1 kHz - 10 MHz frequency range via custom-designed hardware and assessment of the sample is completed in a few seconds. Subsequently, the sample is flushed into a pathology jar to undergo the standard workflow for cytology. The algorithm for extracting the CRF from the measurement was developed based on our previous preclinical study with transgenic KPC mice Samples with a CRF below 1 MHz were considered noncancerous, while CRF values above 1MHz or the absence of a CRF reading were considered cancerous. Results: PC assessment provided by nsCanary was validated against pathology outcomes for each biopsy sample. Findings showing a sensitivity of 86.7% and a specificity of 84.2% are reported in the table. Conclusions: We believe the nsCanary device will provide immediate feedback to the endoscopist on cancer presence and on the adequacy of the sample. This device is intended to support the decision-making process, by enabling clinicians to overcome the challenge of proving cancer presence during the first biopsy procedure, ultimately avoiding revisits and unnecessary trauma.[Table: see text]
Cohort expansion from the phase 1 JEWEL-101 study investigating the tissue factor-targeting antibody-drug conjugate XB002 in patients with advanced solid tumors: Pancreatic and esophageal cancer cohorts.
Authors: Susanna Varkey Ulahannan, Melissa Lynne Johnson, Mia C. Weiss, Andrae L. Vandross, Sofia Luz Vidal-Cardenas, Mustafa Syed, Anthony W. Tolcher
Journal: Journal of Clinical Oncology (2024)

TPS421 Background: Patients (pts) with metastatic pancreatic and esophageal cancers have poor prognosis, with 5-year survival rates of 3% and 6%, respectively (SEER 22). Tissue factor (TF), a factor VIIa receptor involved in initiation of the extrinsic coagulation cascade, is overexpressed in these tumors and has been associated with poor outcomes. XB002 is a novel antibody-drug conjugate (ADC) composed of a high-affinity TF-directed human monoclonal antibody conjugated to the linker-payload zovodotin. Zovodotin consists of an auristatin-based payload with a stable protease-cleavable linker; it is designed to have lower off-target payload deconjugation and improved tolerability versus other auristatin-based ADCs. In preclinical studies, XB002 showed encouraging safety and antitumor activity without affecting coagulation. JEWEL-101 (NCT04925284) is a phase 1, dose-escalation and multi-cohort expansion study evaluating XB002 alone and in combination with nivolumab or bevacizumab in pts with advanced solid tumors. Preliminary results from the dose-escalation stage showed XB002 was well tolerated at multiple dose levels, with low-grade ocular toxicity and no bleeding events or treatment-related peripheral neuropathy (PN). 1 Presented here is the design of the expansion cohorts for pancreatic and esophageal cancers. Methods: Eligible pts must have an inoperable, locally advanced, metastatic, or recurrent solid tumor. Pts with pancreatic adenocarcinoma will receive XB002 single agent. Pts enrolled with esophageal squamous cell carcinoma (ESCC) will be randomized between 2 cohorts to receive either XB002 single agent or XB002 plus nivolumab. All pts in the pancreatic cancer and ESCC cohorts must have ECOG performance status of 0–1, measurable disease per RECIST v1.1, and have received 1–2 prior lines of systemic anticancer therapy, and radiographically progressed during or after their last therapy. Prior immunotherapy is allowed for pancreatic cancer and required for ESCC if locally considered standard of care and pts are eligible. Key exclusion criteria include prior treatment with TF-targeting or auristatin-based ADCs, and significant ocular disorders. Concomitant anticoagulants are permitted, and pts with PN are eligible, provided it is not impacting activities of daily living. The primary objective is objective response rate per RECIST v1.1 by investigator. Secondary objectives include safety, pharmacokinetics, immunogenicity, progression-free survival, duration of response, and overall survival. Enrollment is ongoing in the United States, Europe, and the Asia-Pacific region. 1. Ulahannan et al. ENA 2022. Clinical trial information: NCT04925284 .
Second-line chemotherapy in elderly patients with advanced pancreatic cancer: A mono-institutional retrospective experience.
Authors: Giovanni Trovato, Maria Bensi, Viria Beccia, Alexia Spring, Diletta Barone, Anna Ceccarelli, Serena Perazzo, Gloria Messina, Laura Chiofalo, Cinzia Bagalà, Giuseppe Quero, Sergio Alfieri, Giampaolo Tortora, Lisa Salvatore
Journal: Journal of Clinical Oncology (2024)

606 Background: Only few randomized clinical trials have been conducted for second line therapy in advanced pancreatic cancer (APC). In these studies, elderly patients are poorly represented, even if the median age at diagnosis of APC is increasing; therefore, limited efficacy and safety data are available. Here, we present a retrospective monocentric analysis of second line chemotherapy in elderly patients treated at our Hospital. Methods: This study included patients with APC and aged&gt;70 years old receiving a second-line chemotherapy for APC at our institution from March 2015 to August 2020. The primary endpoints were progression-free survival to second line (PFS2) and overall survival (OS); the secondary endpoint was safety. The Kaplan–Meier method was used to estimate efficacy outcome; log-rank test and Cox-regression model were used to compare the differences, considering a statistically significant p value &lt; 0.05. Results: 169 pts affected with APC received first-line chemotherapy and 61 of them (36%) received second-line therapy. The median age at diagnosis was 74 Years (70-83), 31 (50%) were female; ECOG PS was 0-1 in 44 pts (59%), 41% had at least 2 comorbidities. The regimens of chemotherapy used were: mFOLFOX (28; 46%), Gemcitabine (11; 18%), Capecitabine (15; 24.6%), FOLFIRI (6; 9.8%), mFOLFIRINOX (1; 1.6%). 4 pts (6.6%) had a partial response and 22 (36.1%) had a stable disease, with a disease control rate of 42.7%. The median follow-up was 22.8 months; median PFS2 was 4.5 months (IC 95%: 2.5-6.5) and median OS was 15.4 months (IC 95%: 7.2-23.6). At the univariable analysis, there was a statistically significant difference in mPFS2 according to ECOG PS (0-1 vs 2: 5.3 [IC 95%: 3.5-7.0] vs 2.2 [IC 95%: 1.2-5.4] months; p 0.02) and number of metastatic sites at the beginning of second line therapy (1 vs 2 or more: 5.8 [IC 95%: 4.8-6.7] vs 3.4 [IC 95%: 3.1-3.8] months; p 0.006). At the multivariable analysis, both number of metastatic sites and ECOG PS were confirmed associated with mPFS2. Number of metastatic sites and ECOG PS were both also associated with mOS. No unexpected adverse events were reported, and no patients had to interrupt treatment due to toxicity. Conclusions: In our experience, only about a third of elderly pts with APC received second-line therapy; in these patients, ECOG PS, disease’s burden and the response to therapy are all positive prognostic factors. With regard to the safety profile, older age does not seem to negatively increase serious toxicities. In conclusion, elderly pts should not be precluded from an active treatment (also in later lines setting) and careful patients selection should guide treatment indication.
Diagnostic performance of endoscopy and MRI in identifying true response among patients with rectal cancer treated with total neoadjuvant therapy and selective watch and wait or TME.
Authors: Dana Mohamed Rashid Omer, Hannah Williams, Sabrina T. Lin, Hannah M Thompson, Floris S. Verheij, Jonathan B. Yuval, James T. Buckley, Li-Xuan Qin, Marc J. Gollub, Julio Garcia-Aguilar
Journal: Journal of Clinical Oncology (2024)

28 Background: The success of a watch-and-wait (WW) strategy for rectal cancer relies on restaging endoscopy and MRI to correctly identify a true response (TR) to neoadjuvant treatment. This secondary analysis of the OPRA trial is the first study to evaluate the restaging assessment’s diagnostic performance in a large cohort of WW patients. Methods: In the OPRA trial, patients with stage II/III rectal cancer were treated with total neoadjuvant therapy (TNT) and restaged with endoscopy and MRI 8±4 weeks post-treatment. Patients with a clinical complete (cCR) or near complete (nCR) response were offered WW; patients with an incomplete clinical response were recommended for total mesorectal excision. Diagnostic parameters, including accuracy, sensitivity, specificity, positive and negative predictive values, were calculated using TR as the reference standard. TR was defined as pathologic complete response for patients treated with TME or sustained cCR for ≥2 years for patients on WW. Contingency tables were prepared for two approaches: one considering either cCR or nCR positive for a TR, and one considering cCR as the only response grade positive for a TR. Results: Of the 304 patients restaged after completing TNT, 265 (87.2%) with ≥2 years of follow-up data available were included. Restaging endoscopy outperformed MRI across all parameters. Accuracy improved minimally to 66% when both modalities agreed on a cCR or nCR (Table). Restricting a positive result to cCR resulted in higher specificity, lower sensitivity, and higher accuracy (75%) (Table 1B). The positive posttest probability that a patient with a cCR had a TR was 81%, while the negative posttest probability that a patient with a non-cCR had a TR was 30%. Conclusions: Restaging endoscopy outperforms MRI in predicting TR, but the assessment’s overall accuracy even when both tests are combined remains suboptimal. Our results highlight the challenge of recognizing TR using subjective restaging exams. Opportunities to improve diagnostic accuracy include machine learning and radiomics, which have the potential to aid clinicians in identifying true responders. [Table: see text]
The efficacy of adjuvant chemotherapy after total mesorectal excision with selective lateral pelvic node dissection for lower rectal cancer.
Authors: Shin Kameishi, Toshifumi Yamaguchi, Hiroki Hamamoto, Dai Okemoto, Toru Kadono, Hiroki Yukami, Masahiro Goto, Hiroki Nishikawa
Journal: Journal of Clinical Oncology (2024)

50 Background: The standard strategy for lower rectal cancer (LRC) is neoadjuvant chemoradiotherapy (CRT) plus total mesorectal excision (TME) in Western countries. TME with or without lateral pelvic node dissection (LND) followed by adjuvant chemotherapy is the standard treatment for LRC in Japan. However, the efficacy of adjuvant chemotherapy for LRC after TME without LND remains unclear. The aim of this study was to assess the efficacy of adjuvant chemotherapy for LRC after TME without LND. Methods: We retrospectively reviewed patients who underwent R0 resection by TME without LND and received adjuvant chemotherapy between 2010 and 2020 at our institution. The inclusion criteria were as follows: age ≥ 20 years; histologically confirmed adenocarcinoma; pathological stage III (UICC 8th); lower rectal cancer (Ra/Rb); patients who received adjuvant chemotherapy after R0 resection without LND and no prior treatment before surgery. We evaluated relapse free survival (RFS) and overall survival (OS) in patients with LRC. Prognostic impact of location, adjuvant chemotherapy regimens, T factor, and N factor on RFS was explored by a multivariate analysis. Results: From a total of 197 patients, 117 patients were eligible. Median age was 65 years (range 26–82) and 54 patients (46%) were male. Tumor location was 67 (57%)/50 (43%) for Ra/Rb and pathologic stage was 47(40%) /61(52%)/ 9(8%) for IIIA/IIIB/IIIC. Eighty patients (68%) received fluoropyrimidine monotherapy (single agent) and 37 patients (32%) received oxaliplatin based therapy (doublet) as adjuvant chemotherapy. The 3-year RFS rate and 3-year OS rate were 70.7% (95% CI, 59.0-81.1%) and 94.5% (95% CI, 89.0-98.1%). The 3-year RFS rates according to tumor location (Ra/Rb) and adjuvant chemotherapy regimen (single agent/doublet) were 76.9%/70.7% and 71.8%/68.5%, respectively. The 3-year RFS rates based on pathological stage (IIIA/IIIB/IIIC) were 76.7%/68.4%/64.8%. In a multivariate analysis, T3/4 were identified as an independent poor prognostic factor for RFS (p&lt;0.05). Conclusions: TME without LND followed by adjuvant chemotherapy for patients with LRC demonstrated favorable 3-year RFS rate. adjuvant chemotherapy regimens after TME without LND suggested no additive efficacy of oxaliplatin on RFS.
International real-world study of TOTAL neoadjuvant therapy (TNT) for locally advanced rectal cancer (LARC).
Authors: Alessandro Audisio, Vaneja Velenik, Hélène Meillat, Erika Ruiz-Garcia, Maria Carmen Riesco Martinez, Jeroen Dekervel, Carlos Torres Carvalho, Francisco Javier Suárez, Iva Kirac, Jorge Hernando, Mehmet Artac, Juan Manuel O'Connor, Pètra Braam, Ali Shamseddine, Beatrice Borelli, David Paez Lopez-Bravo, Audrius Dulskas, Francesca De Felice, Alexander Vanden Bulcke, Francesco Sclafani
Journal: Journal of Clinical Oncology (2024)

40 Background: TNT has recently emerged as a standard treatment for LARC. However, use and outcome of the different TNT regimens in real-world practice are largely unknown. Methods: This is an international, multicentre, retrospective study sponsored by the Institut Jules Bordet, Brussels. Eligibility was limited to newly diagnosed LARC patients treated with TNT between March 2013 and May 2023 and outside the context of a clinical trial. The primary objective was to describe real-word practice across international centres. Secondary objectives included treatment safety and efficacy. Data were collected into a central electronic database, and remotely monitored. Descriptive statistics were used, and survival outcomes were estimated with Kaplan-Meier curves. Results: 1,272 eligible patients were included from 47 centres across four continents (Europe, Asia, North America and South America). Baseline characteristics were as follows: 63% males, median age 60 years (range 21-88), 47% low rectum, 26% cT4, 47% cN2, 49% EMVI+, 59% CRM+. In the overall population, 21% of the resected patients had a pathological complete response (pCR), while 11.3% were managed according to a watch-&amp;-wait (w&amp;w) strategy. Median follow-up was 24.1 months (IQR 23.7). Local and distant recurrences after curative-intent surgery occurred in 5.5% and 16.2% of patients, respectively. 3-year event-free survival (EFS) was 68.3%, while 3-year overall survival (OS) was 89%. Serious adverse events were reported in 4.3% of patients during radiotherapy, and in 14.7% during chemotherapy. Patient distribution according to the TNT sequence/regimen, and respective efficacy outcomes are reported in the table. Conclusions: This is the largest real-world study of TNT for LARC. Our findings show substantial variation in the choice of TNT sequence and regimen. Efficacy and safety results are overall in line with those reported in clinical trials, and confirm feasibility of TNT in a real-world setting. Patient recruitment is ongoing, and updated results with propensity score matching analyses will be reported at the meeting. [Table: see text]
Atezolizumab and trastuzumab plus chemotherapy in patients with HER2+ locally advanced resectable gastric cancer or adenocarcinoma of the gastroesophageal junction: A multicenter, randomized, open-label phase II study.
Authors: Zhi Peng, Xiaotian Zhang, Han Liang, Zhichao Zheng, Zhenning Wang, Hao Liu, Jiankun Hu, Yihong Sun, Yanqiao Zhang, Han Yan, Lin Tong, Jiahui Xu, Jessica Xie, Jiafu Ji, Lin Shen
Journal: Journal of Clinical Oncology (2024)

312 Background: Currently, there are no standard perioperative regimens for human epidermal growth factor receptor 2 positive (HER2+) gastric cancer (GC) or gastroesophageal junction (GEJ) cancer. Furthermore, despite advances in neoadjuvant or perioperative chemotherapy, the efficacy of treatment for locally resectable advanced GC or GEJ cancer remains unsatisfactory. To address this need, we evaluated the effectiveness of adding atezolizumab (programmed death ligand-1 inhibitor) to treatment with trastuzumab (a HER2 antibody) + capecitabine and oxaliplatin (XELOX) compared with trastuzumab + XELOX in patients eligible for surgery with HER2+ locally advanced GC or adenocarcinoma of the GEJ. Methods: Patients aged 18–75 years were randomized 1:1 to atezolizumab + trastuzumab + XELOX (Arm A) or trastuzumab + XELOX (Arm B) and received the regimen for three neoadjuvant cycles (3 weeks per cycle) and five adjuvant cycles. Treatment administration was atezolizumab 1200 mg, trastuzumab 6 mg/kg, oxaliplatin 130 mg/m 2 intravenously on Day 1, and capecitabine 1000 mg/m 2 orally twice daily on Days 1–14 of each 3-week cycle. The primary endpoint was the pathological complete regression (pCR) rate. Secondary endpoints were the objective response rate (ORR) during neoadjuvant systemic therapy (NAST) and the R0 resection rate. Time-to-event endpoints are not reported because of immaturity. Efficacy endpoints were analyzed in the intention-to-treat population. The clinical cutoff date for the primary analysis was 12 March 2023. Results: Forty-two Asian patients who provided informed consent were screened and randomized to Arm A (n = 21) or Arm B (n = 21); all patients completed NAST. Most patients were male (92.9%), and the median (range) age was 61 (33–72) years in Arm A and 65 (49–72) years in Arm B. The pCR rate was 38.1% (8/21) in Arm A and 14.3% (3/21) in Arm B (treatment difference: 23.8% [90% confidence interval (CI), 1.3%–44.7%]). The pCR rate was significantly better in Arm A than in Arm B (P = 0.079 &lt;0.1; lower limit of the 90% CI &gt;0). Subgroup analysis showed that age &lt;65 years, male sex, and intestinal Lauren classification were associated with a better pCR rate for the atezolizumab inclusive treatment arm (Arm A); however, these results require further confirmation in future studies. No significant difference was detected between the two arms in ORR during NAST or the R0 resection rate. Conclusions: The addition of atezolizumab to trastuzumab + XELOX therapy was effective in patients with HER2+ locally advanced resectable GC or adenocarcinoma of the GEJ. Clinical trial information: NCT04661150 .
Patient-reported outcomes in patients with gastrointestinal cancer on oral chemotherapy.
Authors: Kevin Juan Zhang, Kian Tehranchi, Emmeline C Academia, Melis Celmen, Jim W Doolin, Mohamad Hotait, Arielle Lasoff, Patricia Tong, Seth J Berkowitz, Andrea J. Bullock, Jessica Ann Zerillo
Journal: Journal of Clinical Oncology (2024)

732 Background: Over the last several years, patient reported outcomes (PROs) have been demonstrated to address patient symptoms, improve outcomes, and reduce health care utilization. We aim to provide an electronic PRO (ePRO) tool for gastrointestinal (GI) oncology patients with the goals of improving adherence, reducing toxicity, and enhancing patient access to the clinical team. Methods: Patients are provided an ePRO tool consisting of a cellphone app integrated into the electronic health record with questions on adherence and 10 questions on symptoms adapted from the NCI PRO-CTCAE for local use. Emails are sent to the clinical team for nonadherence, new or worsening symptoms, or patient requested callback. Outcomes including time to first symptom assessment, emergency department (ED) visit and/or hospitalization at 30 and 90 days from enrollment will be compared with historical controls. Other outcomes including adherence and patient-reported access to the clinic will be assessed. Results: Six patients have been enrolled between May 1, 2023 and September 4, 2023. Five patients were newly starting oral chemotherapy agents and one patient had already been on therapy. Types of cancers included colon cancers (2), rectal cancer (1), pancreatic cancer (1), GIST (1), and cholangiocarcinoma (1). Types of oral chemotherapy included capecitabine (4), olaparib (1), and imatinib (1). Five patients have submitted a total of ten responses. Of the five who completed the ePROs, patients responded a median of one time (range 1-5). Reported symptoms were fatigue (4), pain (2), nausea (1), diarrhea (1), other symptoms (2) and a request callback (1). Seven (70%) responses have prompted emails alerts for clinical symptoms and one (10%) for adherence concerns. All alerts were resolved; average time to alert response 1.6 calendar days (range 1-3). Among historical controls, time to first symptom assessment after a new oral chemotherapy prescription was seven days, 30-day rate for ED and/or hospitalizations was 12%, and 90-day rate of ED visits and/or hospitalizations was 28%. Conclusions: Early data suggests a new process to manage ePROs can provide timely responses to email alerts. Of the responses thus far, 70% prompted email alerts due to clinical symptoms and 10% reported nonadherence, suggesting a high need for ongoing ePRO tools. Results are forthcoming on outcomes including time to symptom assessment/clinical action, ED visit/hospitalization and access.