bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics and outcomes for fecal occult blood test (FOBT) screen detected (SD) versus non-screen detected (NSD) colorectal cancer (CRC).
Authors: Mendis Shehara Ramyalini , Ananda Sumitra S , Hong Wei , Faragher Ian , Croxford Matthew , Jones Ian , Steel Malcolm , Jalali Azim , Gard Grace , To Yat Hang , Lee Margaret , Kosmider Suzanne , Wong Rachel , Tie Jeanne , Gibbs Peter 
Published: January 2021

42 Background: FOBT based screening for CRC has been shown in multiple studies to reduce CRC mortality. Beyond the well described earlier stage at diagnosis, other characteristics of SD cancers have not been well studied. Since 2006 Australians aged 50-74 have regularly been mailed an immunochemical FOBT via the National Bowel Cancer Screening Program (NBCSP), with participation rate stable around 40%. Methods: To explore patient (pt), tumour, treatment and outcome data for SD compared to NSD, we examined a multi-site CRC database where prospectively collected data includes method of detection. Categories include SD via the NBCSP, cases that were symptomatic or incidentally found on imaging (NSD), and cases detected by screening outside the NBCSP (OSD). High risk features for Australian Clinicopathological Staging System (ACPS) Stage B included emergency presentation, T4, lymphovascular invasion and <12 lymph nodes examined. Results: Of 6969 registry pts diagnosed 06/2006–06/2020, 4107 (59%) were aged 50-74, including 473 (12%) SD, 3228 (79%) NSD and 406 (10%) OSD. SD versus NSD pts were younger (mean 62.4 v 64.2 years), had better ASA score (ASA 1-2: 79% v 66%, Odds Ratio [OR] 1.9, p<0.001), earlier stage at diagnosis (ACPS A/B/C/D = 38%/21%/28%/5% v 17%/29%/26%/21%, p<0.001), were more often left-sided (41% v 33%, OR 1.44, p<0.001) but less frequently located in the rectum (28% v 36% OR 0.70, p=0.001). There was no difference by gender. SD tumors were more often well/moderately differentiated (76% v 66%, OR 1.65, p<0.001) and less often mucinous (16% v 20%, OR 0.66, p=0.002). SD stage A tumours were more often T1 (66% v 43%, OR 0.36, p<0.001). SD stage B tumours were more often T3 (92% v 85%, OR 0.43, p=0.033), and had fewer high risk features (60% v 49%, OR 0.64, p=0.036). SD stage C pts had a similar rate of N2 disease (25% v 31%, p=0.20), but more often received adjuvant chemotherapy (96% v 86%, OR 3.6, p=0.002). De novo stage D and relapsed SD pts more often underwent metastatic resection (46% v 25%, OR 2.6, p<0.001). Relapse free survival (RFS) in stage A-C, progression free survival in stage D (PFS), and overall survival (OS) was superior for SD and is in Table. Conclusions: We show for the first time to our knowledge that SD CRCs have many distinct and favourable prognostic features that appear to be driving favourable stage based outcomes when compared to NSD patients. This prognostic data could inform adjuvant therapy decision making and surveillance strategies for SD CRC. [Table: see text]
Olaparib sensitivity observed in metastatic pancreatic cancer (mPaC) with a wide spectrum of germline BRCA1 and BRCA2 mutations (gBRCAm).
Authors: Golan Talia , Kindler Hedy L. , Schatz Philipp , Goranova Teodora , Locker Gershon Y. , Cui Karen , Schlienger Katia , McGuinness David , Williams J. Andrew , Orr Maria , Gutjahr Thorsten , Liu Yu-Zhen 
Published: January 2021

420 Background: The POLO study (NCT02184195) showed that mPaC patients (pts) with a deleterious or suspected deleterious gBRCAm, and whose disease had not progressed during ≥16 weeks of first-line platinum-based chemotherapy, had significantly longer progression-free survival (PFS, primary endpoint) with maintenance olaparib vs placebo: median 7.4 vs 3.8 months, hazard ratio (HR) 0.53; P= 0.004. PFS benefit was observed in pts with g BRCA1m (HR 0.40) and g BRCA2m (HR 0.63). The POLO study represents the largest BRCAm prevalence study in pancreatic cancer . We report additional exploratory analysis to further characterize patient gBRCAm profiles, including the relationship with efficacy. Methods: Pts were enrolled based on either a previously identified gBRCAm status from a local test result and subsequently confirmed by central testing, or a prospectively identified gBRCAm. Pts received maintenance olaparib 300 mg twice daily (tablet) or placebo. PFS was assessed by blinded independent central review (modified RECIST v1.1). Results: Of 3194 prospectively screened pts, a valid BRCA test result was obtained for 3175 (99%) from 12 countries; gBRCAm prevalence was 6.2% in pts not previously known to harbor a gBRCAm (196/3175; 1.6% g BRCA1m, 4.5% g BRCA2m). In countries (n = 8) with > 100 pts prospectively tested, highest gBRCAm prevalence was 9.2% (USA) and lowest 4.0% (Spain). Prevalence by race ( > 100 pts); 6.4% Caucasian, 4.6% Asian. In total, 154 pts with a gBRCAm satisfied all eligibility criteria and were randomized (106 prospectively tested and 48 by local test [44/48 subsequently confirmed by Myriad testing]). 37/154 (24%) randomized pts carried a common Ashkenazi Jewish founder mutation, the majority being from Israel (21 pts). From a total of 151 variants, frameshift mutations were most frequent (g BRCA1m 69.6%, g BRCA2m 71.4%) followed by nonsense mutations (g BRCA1m 6.5%, g BRCA2m 17.1%). The efficacy (PFS) of olaparib vs placebo in the different subgroups are shown in the table. Conclusions: In pts with mPaC enrolled in POLO, g BRCA2m were more prevalent than g BRCA1m and mutation type was predominantly frameshift. PFS benefit was consistent across a heterogenous spectrum of gBRCAm and with the previously reported full analysis set. Clinical trial information: NCT02184195. [Table: see text]
Molecular profiling of advanced pancreatic ductal adenocarcinoma (PDAC): Role of ctDNA.
Authors: Lamarca Angela , McNamara Mairead Geraldine , Hubner Richard , Valle Juan W. 
Published: January 2021

425 Background: Molecular profiling of tumour samples and circulating tumour DNA (ctDNA) may inform treatment of advanced cancer; the role of ctDNA to predict progression-free-survival (PFS) and overall survival (OS) in advanced PDAC is not fully understood. Methods: Eligible patients: those diagnosed with advanced PDAC undergoing molecular profiling [tumour (Foundation Medicine CDx/Caris) or ctDNA (FoundationMedicine Liquid (72 cancer-related genes))]. Baseline patient characteristics and molecular profiling outcomes, including mutant allele frequency (MAF) for pathological alterations were extracted. The primary aim was to assess the impact of presence of ctDNA at time of systemic chemotherapy initiation on PFS and OS. Results: Total of 26 samples (ctDNA 18 samples and 8 tumour samples) from 25 patients diagnosed with advanced PDAC underwent molecular profiling. When the whole population was analysed, the rate of sample analysis failure seemed to be higher when tumour tissue was tested (37.5%) compared to ctDNA (5.56%); p-value 0.072. The overall rate of identification of pathological findings was 72.73%, with 18.18% of patients having targetable findings [EGFRmut (1 patient), KRAS G12C mut (1 patient), FGFR2 fusion (1 patient), RNF43 mut (1 patient)]; these findings impacted treatment management in one patient only (RNF43 mutation; Wnt inhibitor). Variants of unknown significance were identified in 63.64% of samples. Patients with ctDNA analysis at time of palliative chemotherapy initiation (16 samples; 15 patients) were analysed [6 female (40.00%), median age 69.57 years (range 51.61-81.49), metastatic disease (66.67%), 80% first-line (80%), 20% second-line]. Pathological mutations were identified in 9/15 (60.00%) of these patients (KRAS mutation identified in 6/9). After median follow-up of 8.33 months from sample acquisition, 80% and 53.33% of patients had progressed and died, respectively. Median estimated PFS and OS were 5.65 months (95% CI 1.59-8.17) and 7.80 months (95% CI 4.13-not reached). Presence (vs absence) of pathological alterations in ctDNA showed a trend towards shorter PFS (2.91 vs 6.51 months; HR 1.38 (95% CI 0.40-4.77)) and OS (6.12 vs 9.72 months; HR 2.03 (95% CI 0.60-6.82)). Conclusions: This pilot study demonstrates the feasibility of ctDNA analysis in patients with advanced PDAC prior to initiation of palliative therapy. The presence of pathological alterations in ctDNA may prognosticate for worse PFS and OS. Larger studies are required to confirm these findings.
The use of elevated circulating hepatocyte growth factor (HGF) level as a potential prognostic biomarker in locally advanced pancreatic cancer.
Authors: Roberts Hannah Johnson , Wo Jennifer Yon-Li , Yeap Beow Y. , Ulysse Christine A. , Murphy Janet E. , Weekes Colin D. , Ryan David P. , Clark Jeffrey William , Ferrone Cristina R. , Lillemoe Keith D. , Qadan Motaz , Fernandez-del Castillo Carlos , Jain Rakesh K. , Hong Theodore S. , Duda Gabriel Dan 
Published: January 2021

429 Background: The hepatocyte growth factor (HGF)/c-MET pathway has pleiotropic functions in tumor progression including invasion and cancer cell survival. The potential use of circulating plasma HGF as a prognostic biomarker is not known. Methods: This was an analysis of plasma HGF in patients enrolled in a single arm phase II study (NCT01821729) of patients with previously untreated locally advanced pancreatic ductal adenocarcinoma (PDAC) treated with FOLFIRINOX and losartan followed by chemoradiotherapy before resection was attempted (Murphy JE et al., 2019). Eligible patients from the trial included those who had undergone baseline research labs including HGF. Circulating HGF was measured in the plasma on day 1 of treatment using ELISA, and the median value was used to define high vs low levels for the purpose of analysis. The association of elevated HGF with overall survival (OS) was analyzed by univariable and multivariable Cox regression, adjusting for tumor size (≤ versus > 40 mm) and serum CA19-9 (≤ versus > 37 U/mL). Results: There were 46 eligible patients with a median follow up of 31 months. The median age was 63 (range 42-78) and 52% were female (24/46). Median tumor size was 41.4 mm (range 18–68 mm). There were 41/46 patients (89.1%) with elevated baseline CA19-9. Median baseline HGF was 1,250.55 pg/mL (range 650.9–6,459.1). Median OS was 38.4 months for patients with baseline HGF at or below the median, and 19.3 months for those with elevated HGF. On univariate analysis, elevated HGF was associated with poorer OS (HR 2.28, 95% CI 1.06–4.87, p = 0.03). On multivariate analysis, after controlling for tumor size and baseline CA19-9, elevated plasma HGF remained significantly associated with poorer OS (HR 2.58, 95% CI 1.16–5.70, p = 0.02). Conclusions: In conclusion, elevated baseline circulating plasma HGF is an independent biomarker of poorer OS in patients with locally advanced PDAC treated with neoadjuvant therapy. Further randomized studies are needed to define the negative predictive biomarker value for high plasma HGF and identify the optimal HGF range as well as determine applicability to other stages of disease. These results support the continued investigation of plasma HGF in ongoing clinical trials with PDAC patients.
Impact of KRAS alterations in localized pancreatic cancer (PC).
Authors: Shreenivas Aditya Varnam , Annunzio Kaitlin , Kamgar Mandana , Chakrabarti Sakti , Thomas James P. , Madhavan Srivats , Dua Kulwinder , Khan Abdul H. , Hall William Adrian , Erickson Beth , Christians Kathleen K. , Clarke Callisia , Evans Douglas B. , Tsai Susan , Szabo Aniko , Urrutia Raul , Zimmermann Michael T , Reddi Honey V , George Ben 
Published: January 2021

431 Background: Patients (pts) with localized PC do not routinely undergo comprehensive genomic profiling (CGP) unless they develop recurrent or metastatic disease. KRAS is the most frequently mutated gene in PC, however, the impact of different KRAS mutations in localized PC has not been well characterized. We interrogated our genomic database to analyze the KRAS status in PC pts who presented with localized disease at diagnosis (Dx). Methods: We identified PC pts at our institution who underwent CGP utilizing the Foundation One CDx assay and had localized disease at initial Dx; these pts were categorized into resectable/borderline resectable PC (LPC) and locally advanced PC (LAPC). All pts with LPC and LAPC underwent neoadjuvant chemotherapy and chemoradiation prior to possible surgery (all intended therapy - AIT). Tissue from metastatic sites was used for CGP in pts who developed recurrent/metastatic disease before or after completion of AIT. The primary tumor was used for CGP in pts who completed AIT without subsequent relapse or in the absence of adequate metastatic tissue. Effect of each gene on response and survival outcomes was estimated using proportional odds and Cox regression analysis, respectively, adjusting for stage. Results: 75 pts were identified, median age at Dx was 65 years, 59% were male, 65% had a primary tumor in the pancreatic head. 38 (86%) pts with LPC completed AIT compared to 21 (68%) pts with LAPC (p<0.001). KRAS mutation was detected in 95% (71/75) of pts– 94% (67/71) in codon 12 and 6% (4/71) in codon 61. The various KRAS mutations and their association with completion of AIT is summarized in the table. The likelihood of completing AIT did not differ based on KRAS wildtype (WT) vs mutated status (p =1.00), the mutated codon (codon 12 vs. codon 61; p =1.00) or the individual KRAS point mutations (p = 0.7); however, all patients with G12A (N= 1), G12C (N=1), G12L (N=1) and G12R (N=11) mutations completed AIT. KRAS status (mutated vs. WT) and the individual KRAS mutations were not associated with overall survival (OS) after adjusting for stage (p= 0.13 and p = 0.26 respectively). Median OS for patients with LPC and LAPC, was 39 months (mos) and 29 mos respectively. Conclusions: KRAS status and individual KRAS mutations did not have an impact on completing AIT or mOS; however, these findings need to be interpreted with caution due to the inherent biases involved in such analyses. The clinical significance and functional relevance of KRAS G12A, G12C, G12L and G12R mutations, though relatively rare, needs further characterization as well as mechanistic elucidation. [Table: see text]
Development and validation of a radiomics nomogram to discriminate advanced pancreatic cancer patients with liver metastases or other metastatic patterns.
Authors: Hang Junjie , Wu Lixia 
Published: January 2021

435 Background: Pancreatic cancer patients with liver metastases had much poorer prognosis than those with other metastatic patterns. This study aimed to develop and validate a radiomics model to discriminate pancreatic cancer patients with liver metastases from patients with other metastatic patterns. Methods: We evaluated 77 patients advanced pancreatic cancer (APC) with different metastatic patterns and performed texture analysis on the region of interest (ROI). 58 patients and 19 patients were allocated randomly into the training cohort and the validation cohort with almost the same proportion of patients with liver metastases. An independent samples t-test was used for initial feature selection in the training cohort. Random Forest Classifier (RFC) was used to construct models based on these features in both cohorts and a radiomics signature (RS) was derived from the model. Then a nomogram was constructed based on RS and CA19-9, and validated with calibration plot and decision curve. The prognostic value of RS was evaluated by Kaplan-Meier methods. Results: A nomogram based on the RS and CA19-9 was constructed and it demonstrated good discrimination in the training cohort (AUC = 0.93) and validation cohort (AUC = 0.81). Kaplan-meier methods showed that patients with RS>0.61 had much poorer OS than patients with RS < 0.61 in both cohorts. Conclusions:This study presents a radiomics nomogram incorporating both RS and CA19-9, which can be used to discriminate advanced pancreatic cancer patients with liver metastases from patients with other metastatic patterns.
Second primary cancers in patients with sporadic deficient mismatch repair (dMMR) colorectal cancer (CRC).
Authors: Alidina Ayman , Lipton Lara Rachel , Gately Lucy , Skinner Iain , Mendis Shehara Ramyalini , Hong Wei , Dunn Catherine , Cho Jin , To Yat Hang , Steel Malcolm , Jones Ian , Lee Margaret , Tie Jeanne , Kosmider Suzanne , Wong Rachel , Yeung Justin , Gibbs Peter 
Published: January 2021

45 Background: Patients with hereditary non polyposis colorectal cancer (HNPCC) diagnosed with CRC have an elevated risk of a second primary CRC (SPCRC) and of rapid primary cancer development. This informs both initial surgical approach and endoscopic surveillance intervals. A feature of HNPCC is dMMR, also found in 15% of sporadic CRC, where the risk of SPCRC has yet to be defined. Methods: We examined a multi-site comprehensive CRC database (Melbourne, Australia), where prospectively collected data includes family history (including HNPCC), histology, surgery performed and incidence of second primary cancer. Sporadic dMMR included any case with a BRAF V600E mutation, confirmed hypermethylation, negative germline testing, or age over 60 years. We explored the incidence and timing of SPCRC in patients with early stage sporadic dMMR (or MSI-H) versus pMMR cancers. Results: From February 2004 to December 2019, 7442 patients diagnosed with stage I-III CRC were recorded. MMR status was known in 4079 (54.8%), including 714 with dMMR colorectal cancer (17.4%) of which 575 (14.6%) were deemed sporadic dMMR. Sporadic dMMR patients were older (mean 76.2 years vs 65.9 years, p = < 0.001), more likely to be female (65.2% vs 42%, p = < 0.001) and have a right sided primary (80.9% vs 32.8%, p = < 0.001), compared to patients with pMMR CRC. A SPCRC was diagnosed in 11/575 patients (1.91%) with sporadic dMMR CRC versus 27/3365 (0.83%) patients with pMMR CRC (HR = 2.57, 95% CI 1.28 - 5.17, p = 0.008). Median time to SPCRC was 1.13 years vs 2.38 years (p = 0.49). The SPCRC diagnosed in sporadic dMMR CRC vs pMMR CRC were more likely to be dMMR ((72.7%) vs (25.9%), p = 0.03), but a similar number were stage I or II ((81.8%) vs (81.5%)) and a similar number were surveillance detected ((72.7%) vs (77.8%). Conclusions: Patients with sporadic dMMR appear to have a significantly elevated risk of SPCRC compared to the pMMR population and were diagnosed at a shorter interval. The SPCRC is also more likely to also be dMMR. Increased colonoscopic surveillance of patients presenting with an initial sporadic dMMR cancer should be considered where clinically appropriate.
COVID-19 infection in gastrointestinal (GI) cancer patients receiving systemic anticancer treatment (SACT) during the outbreak of the pandemic: The Guy's Cancer Centre experience.
Authors: Tsotra Eirini , Gousis Charalampos , Russell Beth , Moss Charlotte , Palmer Kieran , Montes Ana , Maisey Nicholas R. , Rigg Anne , Owczarczyk Kasia , Qureshi Asad , Harris Victoria , Ross Paul J. , Sarker Debashis , Thillai Kiruthikah , DeNaurois Julien , Roca Jose , Ngan Sarah , Van Hemelrijck Mieke , Sita-Lumsden Ailsa , Dolly Saoirse 
Published: January 2021

455 Background: The COVID-19 pandemic has prompted difficult decisions around the use of SACT. These were based on limited early data suggesting cancer patients receiving SACT were at an increased risk of COVID-19 severe infection and death. Our study aim was to identify the COVID-19 infection and mortality rates of GI cancer patients receiving SACT. Methods: All GI patients receiving SACT at Guy’s Cancer Centre between March, and May 31, 2020 were included. Demographic data (age, ethnicity, socio-economic status (SES)) and cancer characteristics (stage, SACT type, intent and treatment-line) were collected. COVID-19 infection was confirmed by PCR and severity defined by the World Health Organisation (WHO) classification. Patients with clinical or radiological diagnosis alone were excluded. Results: Of 417 GI patients receiving SACT during the study period, 345 (82.7%) received chemotherapy (alone or combined with targeted/biological treatment), 68 (16.3%) targeted/biological treatment alone and 4 (1%) immunotherapy. 14 (3.4%) patients were diagnosed with COVID-19, 13 were on chemotherapy and 1 on targeted/biological treatment. Commonest cancers in the COVID-19 positive group were colorectal (57.1%) and hepatobiliary (21.4%), followed by oesophago-gastric (14.3%) and neuroendocrine tumours (7.1%); 57.1% had stage IV disease. 64.3% of the positive patients were male (compared to 57.3% in the COVID-19 negative population), mean age was 57.7 years (63.1 years) and 85.7% had low SES (79.7%). 8 (57.1%) patients had severe infection and there were 3 (21.4%) COVID-19 related deaths. All the patients who died from COVID-19 were male and were receiving palliative chemotherapy. Only one patient was neutropenic (grade 1) when diagnosed with COVID-19. Conclusions: The rate of COVID-19 infection in our population was relatively low (3.4 %). Of the 14 COVID-19 positive patients, 57.1% had severe infection, 21.4% died (compared to 3.7% mortality in the non-infected group) and all but one were on chemotherapy. This prospective data, from a large UK comprehensive Cancer Centre, provides some evidence that continuing SACT through the pandemic is relatively safe. The risk of COVID-19 related infection and death must be off-set against the cancer-related morbidity and mortality associated with treatment delays.
Deploying an AI-based online search tool to increase patients’ access to and understanding of solid tumor GI clinical trials.
Authors: Kasi Pashtoon Murtaza , Jordan Emily , Jahreiss Luca 
Published: January 2021

456 Background: The number and complexity of clinical trials has been growing, making finding and accessing trials increasingly challenging. Additionally, the goal of representative trial populations remains elusive with sometimes devastating medical consequences. A key barrier to increasing recruitment efficiency is patients’ low awareness of clinical trials as an option. They rarely hear about trials from their oncologists, unless they are based at a research center, which introduces trial population biases by including only patients with good healthcare access. And even if patients decide to search for information on trials themselves, the information is difficult to understand. There are existing trial search tools, but they have multiple shortcomings: complex navigation, limited search functionality, clinical trial data is too complex for non-specialists to understand, and lack of clarity on next steps. Methods: Access to trials via a novel trial search tool (www.ancora.ai) which uses AI to restructure trial information was the main focus of this study. For increased GI cancer specificity, 6 key GI cancers were included into the AI model and information was restructured based on key eligibility differentiators identified (see data structure table). Research participants (xx GI oncology patients) were recruited with the support of patient associations (e.g. The Colon Club) leveraging social media. They were asked to complete a 20 minute survey evaluating both an established tool (clinicaltrials.gov) and the novel tool to find trials relevant for them. They had to assess different aspects of the tools’ usability on a 5-level Likert scale. Survey results were analyzed in MS Excel, using built-in statistical functions (mean, standard deviation, student’s t-test). Results: Please note the survey is ongoing and results will be updated. Current survey respondents had a base level of awareness of clinical trials (3.1±1.2), with patient associations and the internet as leading information sources. The novel tool seemed to make it easier to find trials (3.7±0.9 vs. 2.7±1.3), showed an improvement in ease of understanding information presented (3.8±1.1 vs. 2.6±1.3) and directionally provided more clarity on what next steps towards trial enrollment would be (4.2±0.8 vs. 3.7±1.4). Overall, this led to higher patient satisfaction (3.4±1.1 vs. 2.3±0.5). Conclusions: Novel patient-focused, AI-driven clinical trial support tools can unlock trial access for all patients. Democratizing trial information will not only increase trial accrual, but also patient satisfaction while reducing disparities. [Table: see text]