bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive genomic profiling (CGP)-informed personalized molecular residual disease (MRD) detection: An exploratory analysis from the PREDATOR study of metastatic colorectal cancer (mCRC) patients undergoing surgical resection.
Authors: Nimeiri Halla , Young Amanda , Madison Russell , Fine Alexander D. , Gjoerup Ole , Loupakis Fotios , Fassan Matteo , Lonardi Sara , Sharma Shruti , Wu Hsin-Ta , Aleshin Alexey , Renkonen Elise , Hegde Priti 
Published: January 2022

187 Background: Detection of MRD following metastatic liver resection in advanced CRC patients is associated with poor prognosis with high rate of relapse. Nevertheless, there is currently no standard of care to guide further therapy after curative intent surgery. MRD detection has the promise to be implemented into standard of care and guide treatment decision making. Here we establish feasibility of MRD detection using Foundation Medicine’s novel tissue-informed personalized monitoring assay, FoundationOne Tracker (F1T), in mCRC patients undergoing surgical resection with curative intent. Methods: Tissue-based CGP was performed retrospectively on a cohort of 72 patients from the PREDATOR trial. Trackable patient-specific single nucleotide variants were selected using a novel computational approach negating the need for buffy coat sequencing to filter germline variants. Personalized multiplex PCR was used to detect and evaluate prognostic value of ctDNA from plasma collected at MRD timepoint post-surgery (median 27 days, range 8-99.5). Median follow-up of patients in the overall population was 10.7 months (range: 0.9-53.8 months). Survival analyses were performed using the Kaplan-Meier Estimator and Cox regression. Results: Post-surgical F1T analysis was successful on 96% of cases (69/72). CGP analysis revealed at least one driver mutation in 57% of samples (41/72) including KRAS/NRAS (46%) and BRAF mutations (3%). MRD was detected in 45% (31/69) of patients, of which 94% (29/31) had progressed at the time of the data cut. Median progression -free survival (PFS) was 3.2 months (2.1-7.1) in ctDNA-positive vs 28 months (20.9-NA) in ctDNA-negative population (HR 5, CI 2.7-9.3, p<0.001). Median overall survival (OS) was 31.6 months in ctDNA-positive vs not reached in ctDNA-negative group (HR 27, CI 3.6-205, p<0.001). Conclusions: CGP-informed post-operative MRD detection is a strong prognostic biomarker and correlates with survival outcomes in patients with resected mCRC. F1T is a novel and convenient technological approach to MRD detection utilizing highly validated FMI testing to reveal potentially targetable mutations and inform personalized ctDNA monitoring. These results demonstrate the ability of F1T to accurately detect MRD in mCRC patients following surgical resection, without the need for germline sequencing.
Clinical performance of Immunoscore in stage III colorectal cancer patients in the SCOT and IDEA-HORG cohorts.
Authors: Church David , Sansom Owen , Maka Noori , Edwards Joanne , Oien Karin , Iveson Timothy , Saunders Mark P. , Boukovinas Ioannis , Messaritakis Ippokratis , Moustou Eleni , Chondrozoumaki Maria , Georgoulias Vassilis , Kassambara Alboukadel , Catteau Aurelie , Galon Jerome , Dempsey Laura , Hay Jennifer , Kelly Caroline , Sougklakos Ioannis , Harkin Andrea 
Published: January 2022

196 Background: The ESMO clinical practice guidelines recommend consideration of Immunoscore (IS) for risk assessment of early colon cancer patients. IS clinical performance was assessed in the SCOT and IDEA-HORG trials evaluating 3 vs. 6 months (3m vs. 6m) of mFOLFOX6 adjuvant chemotherapy in stage III colorectal cancer (CRC). Methods: 1,002 formalin-fixed paraffin-embedded (FFPE) tumor samples (762 from SCOT;240 from HORG) were collected, of which 851 were eligible for biomarker analysis. Eligible samples were classified into 2 groups using pre-defined cut-offs (IS-Low, IS- High) and the performance of IS to predict 3 year disease-free survival (3y-DFS) was evaluated. Results: IS was successfully assessed in 846 cases (99%). 615 (72.7%) samples were classified as IS-High (311 and 304 in 3m and 6m arm, respectively). No significant association between IS and patients’ gender, age, PS, BMI or primary tumour location was observed. However, a significant difference between IS-High (43.7%) and IS Low (57.1%) was observed in the proportion of high risk (T4 and/or N2) tumours (p=0.001). Patients with IS-High tumors had significantly longer 3y-DFS (79.4%, 95%CI: 75.9%-82.4%) compared to those with IS-Low tumors (65.0%, 95%CI: 58.3%-70.9%); adjusted hazard ratio (HR) 1.9 (95%CI: 1.46-2.46; p<0.0001). Similarly, IS-High was significantly correlated with longer 3y-DFS in both treatment arms: 78.5% (95% CI 73.4%-82.7%) for IS-High and 65.8% (95% CI 56.1%-73.9%) for IS-Low in 3m arm; 80.3% (95% CI 75.3%-84.5%) for IS-High and 64.4% (95% CI 54.8%-72.6%) for IS-Low in 6m arm. The estimated HRs according to treatment duration and IS classification were 1.80 (95% CI 1.25-2.60) in 3m arm, 2.00 (95% CI 1.38-2.92) in 6m arm and 1.89 (95% CI 1.46-2.47) in the total study population; interaction p = 0.687. Conclusions: The results of this study confirm the prognostic value of IS observed in the IDEA-France trial (Pagès F et al 2020). However, this analysis was not powered to determine the predictive value of IS for treatment duration. Similar analysis of patients treated with CAPOX is warranted.
Early-onset colorectal cancer: Real-world genomic data from the community-based Sarah Cannon Cancer Centers Network.
Authors: Fontana Elisa , Jones Carissa , Misch Amanda , Schlauch Daniel , Spigel David R. , Arkenau Hendrik-Tobias , McKenzie Andrew Jacob 
Published: January 2022

198 Background: Rising incidence in early-onset colorectal cancer (EO-CRC) is a recent phenomenon observed especially in the US. We exploited Sarah Cannon’s web-based analytics platform, to compare the genomic profiles of EO-CRC to late-onset colorectal cancer (LO-CRC). Methods: Commercial NGS testing performed in oncology practices are routinely extracted and harmonized into the Genospace database. Data from CRC adenocarcinomas were selected; patients (pts) with unknown microsatellite instability (MSI) status were excluded. To reduce the confounding effect of MSI-high hypermutated tumors, only MSI-stable (MSS) tumors were analyzed. Reports generated from archival tissue samples were analyzed separately from those generated from plasma, since liquid biopsies were more likely to be post-treatment. Results: NGS reports from 1,477 MSS CRC pts were analysed. Compared to LO, EO pts had same sex distribution and significantly lower prevalence of Caucasian ethnicity (53% LO vs. 43% EO, p < 0.01). 1029 were tissue (18.7% EO) and 448 plasma (17.8% EO) tests. Of 68 CRC-related genes assessed in tissue, 2 were significantly enriched in EO: BRCA1 mutation (3% LO vs. 7.3% EO p 0.01); PTEN mutation (3% LO vs. 6.2% EO p 0.05). Looking at panel-wide gene association, 19 genes (tissue) were enriched in EO, though none were significant after multiple testing correction. In plasma, ATM alterations were significantly higher in LO (17.3% LO vs. 3.8% EO p <0.001, FDR 0.16), (likely clonal haematopoiesis). No difference in tissue nor plasma TMB were observed [tissue: median (IQ): LO 5.04 (3.5 - 7); EO 4.39 (2.5 – 6.1); TMB >10: 7% LO vs. 6% EO; plasma: median (IQ): LO 8.73 (5.7 – 13.4); EO 7.19 (2.9 – 12.6); TMB >10: 12% LO vs. 14% EO]. Overall, tissue and plasma genomic profiles were concordant, except for EGFR alterations (4.5% tissue, 21.6% plasma, possibly acquired amplification post-EGFR therapy). Conclusions: Here we provide real-world insight from pts across the US. In MSS CRC, tissue and plasma genomic profiles of EO pts do not significantly differ from LO pts. Epigenetic and transcriptional events should be investigated. Enrichment for BRCA1 and PTEN mutations in EO pts may have important screening and therapeutic implications; germline status will be further investigated.
Colontown University: Patient-created disease education.
Authors: Seybold Nancy , George Manju 
Published: January 2022

205 Background: PALTOWN’s Facebook community, COLONTOWN, serves over 6,000 colorectal cancer (CRC) patients and caregivers. 81% of members are late stage patients (or late stage caregivers), and 85% are under the age of 60. They are highly motivated to find reliable information about treatment options as quickly as possible. Many arrive with little prior CRC education. Here we illustrate the creation of a patient-centric disease education program, COLONTOWN University (CTU), developed from the conversations and information journeys in COLONTOWN. Methods: CTU is a unique model for disseminating patient-facing disease education. CTU’s patient and caregiver staff develop original resources from a patient perspective, and work with principal investigators, testing companies, and other partners to create content specifically designed for the Learning Centers. Each Center provides resources to address the information needs of patients across both the spectrum of disease education and of CRC disease experience. Within the University’s online platform, self-contained Learning Centers offer structured resource libraries on topics of high interest to patients. Results: CTU creates patient-centric disease education that is accessible and more sophisticated than typical patient education materials. The discussions in COLONTOWN, in groups focused on specific biomarkers, metastases locations, and treatment modalities, provide members with the framework for understanding their disease. CTU gives them the resources they need to have informed discussions with their care teams. The CTU platform provides insight into what resources are most utilized. Survey tools facilitate an understanding of whether patients feel they have access to more treatment options, and have more productive interactions with their care teams, as a result of the education provided by CTU and the conversations with their peers in COLONTOWN. Conclusions: In its first year, CTU has become the education resource of choice for the thousands of members of COLONTOWN. Clinicians, principal investigators, and industry have all been enthusiastic partners in the development of resources. The positive response to CTU demonstrates the value of this model of patient-driven disease education.[Table: see text]
Deviation from the precisely timed age-associated patterns revealed by blood metabolomics to find CRC patients at risk of relapse at the CRC diagnosis.
Authors: Thyparambil Sheeno P. , Zhu Xiurui , Zhang Yani , Sun Hui , Peng Junjie , Cai Sanjun , Li Yaqi , Fu Chen , Bao Pingping , Hao Shiying , Li Zhen , Ding Yun , Yao Xiaoming , Liao Wei-Li , Heaton Robert , Han Zhi , Tian Lu , Schilling James , Sylvester Karl G. , Ling Xuefeng 
Published: January 2022

206 Background: Human serum metabolome profiles have been analyzed to explore the molecular changes that occur with aging. We hypothesized that deep metabolic profiling of sera with different ages would allow the identification of distinct metabolic chronologic patterns as a normal biological baseline to study personal aging. We further hypothesized that metabolic assessment of this chronologic deviation, resulting from advanced precancerous lesion (APL) and stage I/II/III CRC, from the normal reference baseline, would be instrumental for prognosis of relapse revealing underlying pathophysiology. Methods: A cohort of normal (n=3,616, training; n=1,170, testing), 631 advanced adenoma, 1,019 stage I, 404 stage II and 417 stage III serum samples were assembled. Innovative global LCMS metabolomic production were applied to deep profile these subjects. Identification of the age-associated molecular patterns in normal subjects, modeled with an elastic net algorithm, established the reference baseline to mirror a metabolic clock. CRC associated deviation from the precise chronologically paced metabolic patterns was quantified to associate the clinical endpoints of relapse, OSF and PFS, and to identify the tightly associated metabolic pathways. Results: We observed that for those CRCs, the predicted metabolic age can differ from the chronological age with consistent variations, resulting “older” or “younger” metabolic age subgroup in reference to the chronological age. Significant disruptions from the normal baseline were observed in CRCs patients, and consistent stage specific patterns were observed. Outlier, “Older” or “younger” metabolic age subgroup, CRC patients were found with significant future relapse enrichment. Predictive models were derived to case find the patients at risk of future relapse at the CRC diagnosis timepoint. Conclusions: Deviations from the meticulously timed metabolic aging patterns may provide utility to allow prognosis of future clinical endpoints of relapse and overall survival. Close examination of the underlying metabolic pathways, associated with CRC stage specific metabolic patterns, disrupting the baseline ageotypes, not only may improve the sensitivity and specificity of prognostic tests of CRC relapse, but also shed new insights into CRC therapeutics.
Real-world effectiveness and safety of camrelizumab-based neoadjuvant therapy in resectable esophageal cancer: Initial results of a prospective multicenter observational study.
Authors: Zhang Yi , Shen Guoyi , Xu Rongyu , Huang Guozhong , Yang Shengsheng , Zheng Qingfeng , Huang Zhijun , Duan Hongbing , Ma Liangyun , Yang Libao , Yi Yunfeng , Liu Rongxing , Li Kezhi , Chen Shaogeng 
Published: January 2022

250 Background: Camrelizumab, a fully humanized monoclonal anti-PD-1 antibody, has shown promising efficacy with good tolerance in neoadjuvant therapy of resectable locally advanced esophageal cancer (EC). The present study aimed to investigate the effectiveness and safety of camrelizumab-based neoadjuvant therapy in a comparatively larger number of resectable EC patients in a real-world setting and initial results were reported here. Methods: In this prospective multicenter observational study (ChiCTR2000039170), patients with histologically confirmed resectable EC who were scheduled for camrelizumab-based neoadjuvant therapy at the discretion of treating physicians/ oncologists were included. Eligible patients were aged ≥ 18 years, had ECOG PS of 0-1, measurable disease per RECIST v1.1, adequate organ function, and expected survival time of ≥ 3 months, as well as provided written informed consent. The primary endpoint was safety. The secondary endpoints were major pathologic response (MPR), pathologic complete response (pCR), R0 resection rate, overall response rate (ORR), one-year overall survival (OS) rate, and disease-free survival (DFS). Results: At total of 166 patients (62.9 ± 9.2 years, and 84.2% male) were enrolled between October 20 2020 and August 26 2021. All patients received neoadjuvant camrelizumab plus chemotherapies (primarily nab-paclitaxel and nedaplatin) except one receiving camrelizumab alone. Overall, 109 patients (65.7%) experienced treatment-related adverse events (TRAEs), most commonly reactive cutaneous capillary endothelial proliferation (RCCEP, 45.3%), cough (10.4%), and pneumonia (8.5%). Thirteen (7.8%) patients experienced grade 3-4 TRAEs. There was no grade 5 toxicity. At the data cutoff, 141 (84.9%) patients were evaluable for radiological response, 82 (69.5%) patients underwent surgical resection. The ORR was 70.9% (100/141) and the R0 resection rate was 97.5% (79/82). Among the 81 patients available for pathologic assessment, 51 (63.0%) patients achieved MPR and of which, 15 (18.5%) had pCR. The median survival times have not been reached at the time of data analysis. Conclusions: The real-world data of our resectable EC patients showed effectiveness and safety profiles of camrelizumab-based neoadjuvant therapy consistent with those observed in previous trials.
Prognostic value of patient reported outcomes (PROs) in advanced gastroesophageal cancer (GO): A systematic review.
Authors: Naher Sayeda Kamrun , Grimison Peter S. , Siu Ho Wai Derrick , Mercieca-Bebber Rebecca , Stockler Martin R. 
Published: January 2022

251 Background: To summarise the prognostic value of PROs in advanced GO cancer. Methods: We searched multiple databases using search terms developed with medical librarians. Studies examining the relationship between baseline PROs and prognosis were included. Two reviewers screened articles and extracted data on study design, survival, univariable and multivariable relationships between PROs and prognosis. QUAL-SYST was used for quality assessment. Discrepancies were resolved by a third reviewer. Results: Of 3002 abstracts, seven studies were included: four pooled analyses of randomised controlled trials (RCTs), two RCTs and one cohort study. Five received QUAL-SYST scores >65%. Total 3,408 patients and 2,761(81%) with PRO data. Median survival ranged from 4.5 to 9.5 months. In one univariable analysis for oesophageal squamous cell cancer (SCC), physical functioning and fatigue measured by QLQ-C30 had prognostic significance. For adenocarcinoma, physical functioning, global QOL, role functioning, emotional functioning (QLQ-C30) were significant in three studies. Pain was significant in three studies (QLQ-C30 n=2, EQ-5D-3L n=1). Fatigue (QLQ-C30) was significant in two studies. Appetite loss (QLQ-C30) was significant in two studies. In multivariable analyses for oesophageal SCC (QLQ-C30) physical and social functioning had prognostic significance. In adenocarcinoma, physical functioning, role functioning, appetite loss, global QOL, social functioning and pain showed prognostic significance (Table). One study showed adenocarcinoma patients with lower anorexia (FAACT-A/CS scores of >37) lived longer (19.3 months) than patients with low scores ≤37 (6.7 months). Conclusions: Baseline PROs for multiple functional domains, symptoms (pain, appetite loss) and overall QOL have prognostic significance in advanced GO cancer. Further research is needed to establish clear levels of the relationship which could assist in communication with patients about prognosis, and stratification for clinical trials.[Table: see text]
REVIVE study: A prospective observational study in chemotherapy (CTx) after nivolumab (NIVO) therapy for advanced gastric cancer (AGC).
Authors: Matsushima Tomohiro , Narita Yukiya , Misumi Toshihiro , Sakamoto Yasuhiro , Matsuoka Hiroshi , Tanioka Hiroaki , Kawakami Takeshi , Miwa Hiroto , Shoji Hirokazu , Ishiguro Atsushi , Yamada Takanobu , Fushida Sachio , Miura Kou , Shinozaki Katsunori , Mizukami Takuro , Nishina Tomohiro , Moriwaki Toshikazu , Mitani Seiichiro , Nakamura Michio , Muro Kei 
Published: January 2022

257 Background: NIVO therapy is a standard care treatment for heavily pretreated patients with AGC. Improvement in objective response rate (ORR) to CTx after NIVO therapy for various cancer types has been reported. However, the efficacy and safety of CTx for AGC after progression on NIVO remains unclear. Methods: The REVIVE trial was a prospective, multicenter, observational study that evaluated the efficacy and safety of CTx in NIVO-refractory or NIVO-intolerant patients (pts) with AGC (UMIN000032182). The primary endpoint was overall survival (OS) of CTx following NIVO therapy. The median threshold and expected survival times were set as 4.0 and 7.0 months (M). The secondary endpoints are ORR, disease control rate (DCR), progression-free survival (PFS), and incidence of adverse events (AEs), including immune-related adverse events (irAEs). CTx consisted of irinotecan alone (IRI), trifluridine/tipiracil alone (FT), and oxaliplatin-containing regimens (OX). Results: Of 395 pts treated with NIVO who met the eligibility at formal registration from Jun 2018 to Sep 2020, 199 pts who received CTx after NIVO were evaluated. Pt characteristics were as follows: median age, 69 years; male, 70%; ECOG PS 0/1/2, 38/51/12%; histology (diffuse/intestinal), 39/59%; metastatic lesions (peritoneum/liver/lung), 38/34/15%; number of metastatic organ sites (0–1/≥2), 40/60%; measurable lesions, 83%; and CTx regimens (IRI/FT/OX), 64/31/5%. Median OS and PFS were 7.5 M (95%CI, 6.7–9.7) at 145 events for OS and 2.9 M (95%CI, 2.2–3.5) at 184 events for PFS. The ORR and DCR were 17.0% (95%CI, 11.6–23.6) and 46.7% (95%CI, 38.9–54.6). Median OS, median PFS, ORR, and DCR according to CTx regimens (IRI/FT/OX) were 8.1/7.1/6.2 M, 3.3/2.8/2.4 M, 18.9/10.9/25.0%, and 47.8/43.5/50.0%, respectively. At the start of CTx, 42 pts had irAEs due to prior NIVO therapy. The most common any-grade and grade ≥3 AEs during CTx included decreased appetite (46% and 7.5%), fatigue (26% and 2.5%), nausea (24% and 1.5%), constipation (16% and 0%), and diarrhea (28% and 4.0%). No treatment-related deaths were observed. Conclusions: Prior NIVO therapy may lead to improved prognosis after CTx without unexpected AEs in pts with AGC, warranting further investigations after NIVO is approved as first-line treatment.[Table: see text]
Examining value-based care outcomes in gastric and esophageal patients with and without access to registered dietitians: A retrospective cohort study of patients enrolled in the oncology care model.
Authors: Smith Karen , Torres Vanessa , Jensen Terry Lynn , Ortega Lance , Hudson Kathryn Elizabeth , Hoverman John Russell , Wilfong Lalan S. 
Published: January 2022

264 Background: Patients with gastric and esophageal cancers are at high risk for malnutrition. Appropriate nutrition care provided by a registered dietitian (RD) as part of a multidisciplinary care team is supported by evidenced-based guidelines and clinical studies focused on surgical outcomes. However, Medicare does not routinely cover outpatient RD services for oncology patients which limits access to this care. Examining quality outcomes for patients in clinics with and without access to a RD can help define the value of this service. Methods: We used a retrospective cohort design to analyze Total Cost of Care (TCOC), hospital admissions and Length of Stay (LOS), and Emergency Department (ED) and Observation visits for patients with gastric and esophageal cancer who were enrolled in the Oncology Care Model (OCM) during Performance Periods (PP) 1-6 (July 1, 2016 – June 30, 2019). We divided patients from a geographically concentrated metropolitan hub into cohorts based on clinic access to a RD. Each patient’s initial OCM episode of care was used for analysis. Results: We identified 253 OCM patients with gastric or esophageal cancer from PP1-6. Of these, 109 were treated at 9 clinics with an RD and 144 in 16 clinics without a RD. In the RD cohort 42.2% of patients were admitted to the hospital with a LOS of 6.8 days. In the non-RD cohort 45.8% of patients were admitted to the hospital with a LOS of 9.4 days. TCOC for the 6-month episode was lower in the RD cohort at $ 39,033 vs the non-RD cohort at $49,359. There were 0.56 ED and observation visits per patient in the RD cohort and 0.8 ED and observation visits per patient in the cohort without a RD. Conclusions: Amongst OCM patients with gastric and esophageal cancers, treatment at a clinic with a RD was associated with lower TCOC, reduced LOS for patients that were admitted to the hospital and fewer ED and observational visits. This analysis shows the potential benefit of RD services in an outpatient setting and justifies further study. Future prospective studies will need to evaluate which interventions are most impactful.[Table: see text]