bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic significance of serum CA 19-9 response and dynamics in patients with intrahepatic cholangiocarcinoma undergoing surgical resection.
Authors: DiPeri Timothy P. , Newhook Timothy E. , Tzeng Ching-Wei D. , Chun Yun Shin , Lee Sunyoung S. , Javle Milind M. , Vauthey Jean-Nicolas , Tran Cao Hop Sanderson 
Published: January 2022

479 Background: Pre and post-operative elevation of serum CA 19-9 have been associated with poor outcomes and increased risk of recurrence in patients with resected intrahepatic cholangiocarcinoma (ICC). We sought to investigate the impact of CA 19-9 response and dynamics on survival for patients with ICC undergoing surgical resection. Methods: Clinicopathologic characteristics were abstracted from a prospectively maintained database at a tertiary cancer care center for patients with ICC undergoing surgical resection from 2003 to 2020. Exclusion criteria included CA 19-9 non-producers (≤ 1 U/mL at baseline), missing baseline/pre-operative or postoperative CA 19-9 value, or total bilirubin > 2 mg/dL. Overall (OS) and recurrence-free survival (RFS) was compared among patients when categorized by baseline (neoadjuvant)/pre-operative (upfront surgery) and post-operative CA 19-9 values: normal (> 1 to 37 U/mL), intermediate (> 37 to 200 U/mL), and elevated (> 200 U/mL). Patients were then stratified by perioperative CA 19-9 response (responder [non-normal to normal CA 19-9 OR 50% reduction in CA 19-9; normal to normal CA 19-9], non-responder [non-normal to non-normal CA 19-9 OR < 50% reduction in CA 19-9; normal to non-normal CA 19-9]) and CA 19-9 dynamics (normal to normal, non-normal to normal, non-normal to non-normal, normal to non-normal CA 19-9 values). Results: A total of 112 patients were identified including 67 (59.8%) who underwent upfront surgery and 45 (40.2%) who received neoadjuvant therapy. Patients with a normal CA 19-9 at diagnosis had median RFS and OS durations of 61 and 163 months, followed by intermediate CA 19-9 (20 and 98 months) and elevated CA 19-9 (18 and 46 months, p = 0.308 RFS; p = 0.295 OS). Those who had a normal CA 19-9 post-operatively had the best median RFS and OS (46 and 163 months), followed by intermediate CA 19-9 (13 and 58 months) and elevated CA 19-9 (5 and 8 months, p = 0.059 RFS; p = 0.005 OS). When stratified by perioperative CA 19-9 response, responders had a median RFS of 36 vs. 13 months in non-responders (p = 0.143), and a median OS of 98 months vs. 88 months in non-responders (p = 0.077). Patients with normal CA 19-9 post-operatively had longer RFS/OS (normal to normal, 48/98 months; non-normal to normal, 30/not estimable months) than those who had non-normal CA 19-9 both pre- and post-operatively (non-normal to non-normal, 7/34 months, p = 0.018 RFS; p = 0.007 OS). Conclusions: Patients with normal CA 19-9 levels post-operatively, who had either normal or elevated CA 19-9 pre-operatively, had the greatest RFS and OS durations. A normal (or normalized) post-operative CA 19-9 may inform patient-centered decisions on adjuvant therapy and/or surveillance intensity.
Meta-analysis of surrogate endpoints for survival in patients with unresectable hepatocellular carcinoma treated with immune checkpoint inhibitor-based regimens.
Authors: Zhu Andrew X. , Lin Yong , Ferry David Raymond , Widau Ryan C , Saha Abhijoy 
Published: January 2022

483 Background: Overall survival (OS) remains the gold standard for demonstrating clinical benefit in advanced hepatocellular carcinoma (HCC). While surrogate radiology-based endpoints for OS, such as progression-free survival (PFS) and objective response rate (ORR) are commonly used in the field of oncology, they remain controversial in the setting of HCC where antiangiogenic agents were the mainstay of treatment until recently. Immune checkpoint inhibitors (CPIs) as monotherapy or in combination have shifted the treatment paradigm in HCC. We investigated the surrogacy of radiology-based endpoints from CPI clinical trials in advanced HCC. Methods: Study level data were collected for disclosures published in EMBASE, PubMed, Clinicaltrials.gov and conference abstracts. Keywords used included (abbreviated here): immune CPIs, advanced or metastatic HCC and ORR, PFS and OS. Key inclusion criteria included: Phase I, II and III trial data, and patients with advanced or metastatic HCC who received CPI monotherapy or in a combination regimen. The endpoints investigated were median OS (mOS), median PFS (mPFS) and ORR (RECIST v1.1). A weighted Pearson correlation coefficient, with weights corresponding to the number of patients in the different treatment arms of the trials, was calculated between ORR/mOS, ORR/mPFS and mPFS/mOS in all arms, arms that included only patients with Child-Pugh A liver function, and arms in the first-line therapy setting. 95% confidence intervals (CIs) based on the empirical bootstrap re-sampling method are also reported. Results: Eighteen clinical trials (8 randomized trials and 10 multi-cohort trials) published between 2017 and 2021, including 3,246 patients across 32 treatment arms, were selected for inclusion in this meta-analysis. Ten trials included CPI monotherapy arms, 5 trials included CPI + TKI arms, 4 trials included CPI + anti-angiogenic monoclonal antibody arms, and 2 trials included CPI + CPI arms. There was 1 CPI + chemotherapy arm and 1 CPI + CPI + TKI arm in separate trials. Weighted Pearson correlation coefficients and corresponding 95% CIs are presented in the table. Conclusions: Our analysis suggests ORR/mOS, ORR/mPFS, and mPFS/mOS are positively correlated, with ORR/mPFS more strongly correlated compared to the other pairs, in patients with advanced HCC who were treated with CPI-based regimens. [Table: see text]
Neuroendocrine tumors: Ten years of experience in a Mexican oncology reference center.
Authors: Torres-Cisneros Eduardo Rey , Burguete-Torres Alan , Buenaventura Cisneros Sergio , Bruni-Guerrero Carla Renata , Wimer-Castillo Blanca Otilia , Hernández-Barajas David , Vidal-Gutiérrez Oscar , Salazar-Mejía Carlos Eduardo 
Published: January 2022

503 Background: Neuroendocrine tumors (NETs) are infrequent neoplasms that originate in the neuroendocrine cells of the embryological endoderm. Few data exist about the epidemiology and clinical characteristics of these tumors in the Mexican population. Methods: We performed a retrospective analysis of patients with pathology-confirmed NET treated at an Oncology Reference Center in North-East Mexico from 2010 to 2019. Clinical characteristics were recorded and an evaluation of overall survival (OS) using the Kaplan-Meier method was performed. Results: Fifty-three patients were included in the final analysis. The mean age at diagnosis was 54 +/- 16.36 years and 53% were men. Primarily affected sites were the gastroenteropancreatic tract [GEP] (47%), lung and mediastinum (21%), unknown primary (21%), and others (11%). Regarding the clinical stage at presentation, 22.6% of patients with NETs had localized disease, while 22.6% had regional spread and 54.7% were considered to have metastatic disease at diagnosis. Median OS was 42 months for all patients with NETs. In the GEP group, the median OS was 64 months, whereas for the lung/ mediastinum group was 8 months and for the unknown primary group was 5 months. Median OS stratified by stage was as follows: Localized disease: Not reached (NR), locoregional (20 months), and metastatic disease (8 months). Conclusions: To our knowledge, this is the first study published in English literature reporting the clinical characteristics and survival of Mexican patients with NETs. It is necessary to expand the information regarding these neoplasms to improve access of these patients to standard treatments and therefore improve their outcomes.
Treatment response and clinical outcomes of neuroendocrine neoplasms treated with immune checkpoint inhibitors: A single-institution experience.
Authors: Hauser Haley , Le Tiffany , Chou Joanne F. , Heffernan Olivia , DeMore April , Gonen Selin , Capanu Marinela , Reidy Diane Lauren , Raj Nitya Prabhakar 
Published: January 2022

506 Background: Immune checkpoint inhibitors (ICIs) have antitumor activity in some solid tumors, however a role for ICI’s in the treatment of neuroendocrine neoplasms (NENs) is uncertain. We analyzed response and outcomes of NENs, both well differentiated neuroendocrine tumors (WDNET) and poorly differentiated neuroendocrine carcinomas (PDNEC), treated with ICIs at Memorial Sloan Kettering Cancer Center during the past decade. Methods: Patients with NENs who received ICIs between 2010-2021 were identified. Demographics, pathology characteristics, treatment response and outcomes were recorded. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods. Analysis of next-generation sequencing (NGS) results from archival tumor tissue was performed. Results: 57 patients with NENs treated with ICIs were identified (WDNET-16; PDNEC-41). All patients had heavily-treated metastatic disease (median number of prior systemic treatments, WDNET-4, PDNEC-2). Median time from diagnosis to ICI treatment was 41.5 months in WDNET, 8 months in PDNEC. WDNET response: 1 (6%) partial response (PR), 4 (25%) stable disease (SD), 10 (63%) progressive disease (PD). PDNEC response: 6 (15%) PR (5 microsatellite stable, 1 unknown), 3 (7%) SD, 32 (78%) PD. Median duration of ICI treatment: 2 months (range 0-27) in WDNET, 1 month (range 0-16) in PDNEC; median duration of treatment for the 7 responders was 11 months (range 2-27). While receiving ICIs, 3 PDNEC responders developed PD in an escape lesion (2 brain, 1 nodal) after response in all other disease sites and successfully continued ICI treatment post-RT of escape lesion. Six-month PFS was 20% [95%CI: 7%-55%] and 9.8% [95%CI: 4%-25%], OS 60% [95%CI: 40%-91%] and 37% [95%CI: 25%-56%], respectively in WDNET and PDNEC. NGS results were available in archival tumor tissue of 35 patients (61%); most common alterations were TP53 (20/26, 77%) and RB1 (14/26, 54%) in PDNEC versus ATM, SMAD4, CREBBP, and IRS2 (all 1/9, 11%) in WDNET. Conclusions: We observed limited activity for ICI’s in NEN treatment, primarily restricted to a subset of PDNEC. PFS/OS findings were consistent with historical data, reflecting the pathogenesis of distinct NEN subtypes.
A natural history of gastroenteropancreatic neuroendocrine tumors evaluated at a tertiary cancer center: An observational study of 2,067 cases.
Authors: Powers Benjamin Daniel , Ahmad Yaser , Diaz Gabriel , Tarhan Ozlem , Al-Toubah Taymeyah E. , Haider Mintallah , Fleming Jason B. , Strosberg Jonathan R. , Anaya Daniel A. 
Published: January 2022

508 Background: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are the second most prevalent digestive cancer and are increasing in incidence. With relatively indolent tumor growth, survival is often long, even for patients with metastatic disease. However, few studies have assessed long-term survival. Therefore, we analyzed the overall survival (OS) of a cohort of GEP-NET patients at a tertiary cancer center from 2000-2015. Methods: 2,707 patients with a pathologic diagnosis of GEP-NET were identified. 640 patients presented for second-opinion visits and were excluded, leaving 2,067 patients, of whom, 2,053 had vital status data for analysis. Primary sites included jejunum/ileum (small bowel), pancreas, gastric, colorectum, appendix, duodenum, and unknown. OS time was calculated from the date of pathologic diagnosis to the date of last follow-up or death. The reverse Kaplan-Meier method was used to calculate follow-up time. Vital status was identified through linkage to the Florida Cancer Registry. Kaplan-Meier (KM) curves and log-rank test were used for OS analyses. Results: The median age of the cohort was 60.7 years. The median follow-up time was 148.9 months (12.4 years). 1,431 (69.2%) patients presented with distant metastatic disease. Most patients, 1,351 (65.5%), underwent treatment at another facility before presentation. The median OS was 132.2 months (11.0 years) for the cohort and was 108.0 and 245.5 months for patients presenting with and without metastasis, respectively (p < 0.001). For metastatic patients, unknown primary tumor site was associated with the worst median OS (55 months), followed by rectal (77 months), gastric (84 months) and pancreatic (85 months; p < 0.001). Duodenal and small bowel had the longest median OS at 147 and 143 months, respectively. Surgery for metastatic disease had an OS benefit (155.7 months) compared to no surgery (98.3 months). Conclusions: In a large cohort of predominantly metastatic GEP-NET patients with extended follow-up time, median OS was over 11 years and 9 years for patients with metastatic disease. These results suggest that OS at a tertiary cancer center may be greater than historical national administrative analyses when given adequate follow-up time, which is important to avoid bias in survival estimates.[Table: see text]
Risk of myelodysplastic syndrome/acute leukemia with sequential capecitabine/temozolomide and 177Lu-dotatate.
Authors: Al-Toubah Taymeyah E. , Pelle Eleonora , Strosberg Jonathan R. 
Published: January 2022

513 Background: The treatment landscape for neuroendocrine tumors includes alkylating-agent chemotherapy and peptide receptor radiotherapy (PRRT) with 177Lu-Dotatate. The risk of MDS/AML associated with 177Lu-Dotatate is approximately 2-3%. Several small prior studies have suggested substantially higher rates of MDS/AML (approximately 10%) in patients who have also received alkylating agent chemotherapy with streptozocin or temozolomide, either combined with PRRT or sequentially. Methods: Retrospective study of all patients with advanced NENs treated at the Moffitt Cancer Center between 1/2008 and 9/2019 who received treatment with CAPTEM. Results: 462 patients received treatment with CAPTEM, among whom 49 received also received PRRT. Median follow-up was x months. 4 patients developed MDS/AML, all of whom had also received both CAPTEM and PRRT. None of the patients who received CAPTEM chemotherapy without PRRT developed a long-term hematological malignancy. Conclusions: 8% of patients who received both CAPTEM and PRRT developed MDS or AML, a risk that is higher than that associated with PRRT alone. This cumulative risk needs to be considered when sequencing treatments in NETs.
Association of personalized and tumor-informed ctDNA with patient survival outcomes in pancreatic adenocarcinoma.
Authors: Botta Gregory P. , Abdelrahim Maen , Aushev Vasily N. , Esmail Abdullah , Drummond Bridgette , Sharma Shruti , Kalashnikova Ekaterina , Hook Nicole , Chandana Sreenivasa R , Tejani Mohamedtaki Abdulaziz , Malla Midhun , Schafer Liudmila N. , Kasi Pashtoon Murtaza , George Giby V. , Aleshin Alexey , Dayyani Farshid , Hanna Diana L. 
Published: January 2022

517 Background: Pancreatic adenocarcinoma (PDAC) is the third leading cause of cancer-related death, with a recurrence rate of 85% after curative surgery and a 5-year survival rate of 10%. Serum biomarkers like CA 19-9 lack sensitivity and specificity (10% of patients fail to produce CA 19-9), and are poor indicators of molecular residual disease (MRD). Circulating tumor DNA (ctDNA) detection allows for MRD identification months ahead of radiological findings, and may assess molecular response and patient outcomes. Methods: A personalized and tumor-informed multiplex PCR assay (Signatera™ bespoke mPCR NGS assay) was used for the detection and quantification of ctDNA in a prospective clinical cohort of patients. Serial time points were collected for unresectable, borderline resectable, and resectable subsets of patients to monitor ctDNA levels in response to treatment (see Table). Results: 93 patients were included, with a median age of 67.3 yrs and 45% female. 285 timepoints were analyzed for ctDNA presence, with each patient having between 1 and 7 timepoints (median 3 timepoints per patient). 46 patients had one or more samples positive for ctDNA, resulting in an anytime ctDNA positivity rate of 49.5%. Anytime positivity correlated with the stage of disease (p<0.001). Within ctDNA-positive samples, observed levels were 0.04-1227 mean tumor molecules per mL of plasma (mean 35.1, median 1.02 MTM/mL). During the follow-up period (median 13.5 months, range 1-80 months), 36 patients had recurrence or disease progression events. Recurrence-free survival (RFS) strongly correlated with post-operative anytime ctDNA positivity: Hazards Ratio 8.0 (95% CI 3.4-18.7), p =1.6e-6. For 49 patients, CA 19-9 measurements were available. Elevated CA 19-9 was not correlated with RFS (p=0.35). Conclusions: Our study demonstrates the feasibility of tumor-informed ctDNA-based MRD testing in PDAC, in 93 patients of all stages. ctDNA positivity correlated with patient survival outcomes more strongly than CA19-9. Our data suggests patients can benefit from personalized and tumor-informed MRD testing.[Table: see text]
Liquid biopsy for diagnosis in patients with suspected pancreatic and biliary tract cancers: PREVAIL ctDNA pilot trial.
Authors: Mencel Justin , Feber Andrew , Begum Ruwaida , Carter Paul , Smalley Michaela , Bourmpaki Elli , Shur Josh , Zar Sameer , Kohoutova Darina , Popat Sanjay , George Angela , McVeigh Terri Patricia , Hubank Michael , Peckitt Clare , Fribbens Charlotte Victoria , Watkins David J. , Rao Sheela , Chau Ian , Cunningham David , Starling Naureen 
Published: January 2022

522 Background: Most patients with pancreatic cancer (PC) and biliary tract cancer (BTC) present with advanced disease. In confirmed cases, circulating tumour DNA (ctDNA) may be detected through liquid biopsy in 80-90%. Obtaining a diagnostic biopsy can be technically challenging, require complex invasive procedures and may not be feasible due to comorbidity. Reduction in capacity of aerosol generating diagnostic procedures in many healthcare systems due to COVID19 has highlighted the unmet need for simple, non-invasive diagnostic tools. We piloted the use of ctDNA to support the diagnostic pathway in patients with suspected cancer across 6 tumour types, here we present its use in PC/BTC. Methods: This single centre prospective cohort pilot trial was conducted at the Royal Marsden from June 2020 to August 2021. 16 patients were planned each in the PC and BTC cohorts. Eligibility included radiologically suspicious PC/BTC without histological diagnosis, patients with prior non-diagnostic biopsy and inaccessible tumours. Liquid biopsy for ctDNA was collected for plasma based next generation sequencing, using a custom 59 gene panel of common variants in PC/BTC tumours, including analysis for somatic, copy number and structural variants. Clonal haematopoiesis of indeterminate potential (CHIP) and germline variants were identified and subtracted. A molecular tumour board (MTB) reviewed results for interpretation and clinical context. Primary outcome was the proportion of patients with a ctDNA result consistent with a diagnosis of malignancy following MTB discussion. Results: 32 patients with suspected PC (n= 16) and BTC (n=16) were recruited. Baseline characteristics are shown in table. ctDNA was detected in 69% and 56% of patients with suspected PC and BTC respectively. MTB discussion confirmed all variants detected were consistent with a diagnosis of malignancy. At the time of data cut off, 23 patients had a subsequent biopsy. The sensitivity and specificity of ctDNA as a diagnostic tool was 80% (90% CI 49.3-96.3) and 100% (90% CI 36.8-100) for PC respectively, and 100% (90% CI 60.7-100) and 75% (90% CI 24.9-98.7) for BTC respectively. There were 2 false negatives in the PC cohort subsequently diagnosed with PC, and 1 false positive in the BTC cohort subsequently diagnosed with oesophageal cancer. Conclusions: ctDNA can be used to support a diagnosis of cancer in patients with radiologically suspected PC/BTC. A blood first, tissue second strategy in the diagnosis of PC/BTC could improve diagnostic efficiency, speed, and add resilience to the current diagnostic pathway. Clinical trial information: NCT04566614. [Table: see text]
Hypofractionated radiotherapy to the pancreas: U.K. experience.
Authors: Teoh Suliana , Sabbagh Ahmad , Wadsley Jonathan , Low Lori , Harrison Claire , O'Hare Jolyne , Goody Rebecca , Summers Kitty , Wilson David , Walther Julie , Wilson Fiona , Radhakrishna Ganesh , Aitken Katharine , Owens Rob , Mukherjee Somnath 
Published: January 2022

525 Background: During the COVID19 pandemic, many centres in the UK, shifted towards utilising hypofractionated radiotherapy (RT) to pancreas. We aim to report the UK experience in hypofractionated radiotherapy to the pancreas in 2020. Methods: We retrospectively identified patients receiving either moderate hypofractionated (15 fractions) or ultra-hypofractionated (3-5 fractions) RT to the pancreas from 7 centres in the UK. Rates of toxicity, progression, death and potential prognostic factors were assessed. Univariate and multivariate Cox proportional hazards analyses were performed. Results: 92 patients from 7 centres were included in the analysis (median age 71 (range 49-88). 90% had performance status of 0-1. 66% had locally advanced disease. 53% had RT delivered over 3-5 fractions (n = 49, median: 30Gy/5f, range:30-40Gy in 3-5f). The rest had 15-fraction RT with or without concurrent chemotherapy (n = 43, median: 45Gy/15f, range: 36-45Gy/15f). Induction chemotherapy (CT) was used in 64% (FOLFIRINIOX –42/59). Median follow-up was 13 months from first treatment (induction CT or RT). Median overall survival (OS) among all patient was 17 months, (95% CI-14.5-19.5 months). On multivariable analysis, induction CT was the only predictor of improved PFS (median survival (MS) 12 vs 5 months; hazard ratio [HR] 0.23; 95% confidence interval [CI]: 0.12-0.44, p < 0.001) and OS (MS 24 vs 11 months; HR 0.15; 95% CI: 0.07 – 0.34, p < 0.001). There were no deaths. 4 patients had grade 3+ toxicities (transaminitis, cholecystitis and gall bladder perforation, small bowel obstruction and diarrhoea) –all had concurrent CT. Conclusions: Our survival outcome appears to be comparable with published data from CT + concurrent chemoradiotherapy. Induction CT appears to improve outcome. Careful selection of patients can help maximise advantage in this patient population.