bluuebunny/crossref_metadata_2025_split huggingface dataset:
Consensus molecular subtypes and CRCassigner classifications in metastatic colorectal cancer (mCRC): Prognostic and predictive impact in the TRIBE2 study.
Authors: Borelli Beatrice , Fontana Elisa , Giordano Mirella , Antoniotti Carlotta , Bergamo Francesca , Murgioni Sabina , Pietrantonio Filippo , Morano Federica , Tamburini Emiliano , Boccaccino Alessandra , Santini Daniele , Conca Veronica , Pella Nicoletta , Maiello Evaristo , Ugolini Clara , Fontanini Gabriella , Falcone Alfredo , Nyamundanda Gift , Sadanandam Anguraj , Cremolini Chiara 
Published: May 2020

4016 Background: The TRIBE2 study (NCT02339116) recently demonstrated the superiority of upfront FOLFOXIRI/bevacizumab (bev) when compared to a pre-planned strategy of doublets/bev in molecularly unselected but mostly (74%) RAS/ BRAF mutant mCRC patients. The Consensus Molecular Subtypes (CMS) and CRCAssigner (CRCA) demonstrated prognostic value in multiple studies, but their predictive role has not been established so far. Given the poor prognosis associated with early stage mesenchymal/stem-like subtypes, we hypothesized that the CMS/CRCA classifiers could predict benefit from the upfront intensified strategy in patients included in the TRIBE2 study. Methods: Untreated formalin-fixed paraffin-embedded samples were classified into CMS/CRCA subtypes using a custom nCounter assay (NanoString Technologies). The impact of subtypes on progression free survival (PFS), progression free survival 2 (PFS2, defined as the time from randomization until the second evidence of disease progression) or overall survival (OS) was evaluated in the profiled population. Results: 426 and 428 (63%) patients enrolled in the TRIBE2 study were profiled according to CMS and CRCA classifications, respectively. The distribution of CMS/CRCA subtypes differed according to primary tumour site (both p < 0.001 for CMS/CRCA) and RAS/ BRAF mutational status (both p < 0.001 for CMS/CRCA). Significant associations of both CMS/CRCA classifiers with PFS, PFS2 and OS were demonstrated (Table). The effect of treatment intensification was independent of CMS subtypes (p for interaction for PFS/PFS2/OS: ns). Significant interaction effect between CRCA subtypes and treatment arm was reported in terms of PFS (p = 0.017), PFS2 (p = 0.010) and OS (p = 0.008). The benefit from the intensification of the upfront chemotherapy seemed more relevant in the stem-like (PFS, HR = 0.60; p = 0.03) and mixed subtypes (HR = 0.44; p = 0.002). Conclusions: CMS subtypes have a prognostic role in mCRC independently of RAS/ BRAF status. CRCA classification may help identifying subgroups of patients who may derive a more substantial benefit from upfront FOLFOXIRI/bev. [Table: see text]
Pembrolizumab monotherapy for patients with advanced MSI-H colorectal cancer: Longer-term follow-up of the phase II, KEYNOTE-164 study.
Authors: Diaz Luis A. , Le Dung T. , Kim Tae Won , Van Cutsem Eric , Geva Ravit , Jaeger Dirk , Hara Hiroki , Burge Matthew E. , O'Neil Bert H. , Kavan Petr , Yoshino Takayuki , Guimbaud Rosine , Taniguchi Hiroya , Elez Elena , Al-Batran Salah-Eddin , Boland Patrick M , Cui Yi , Mayo Carlos Alberto , Marinello Patricia , Andre Thierry 
Published: May 2020

4032 Background: Pembrolizumab provides effective antitumor immunity and durable responses in patients (pts) with advanced, colorectal cancer (CRC) with microsatellite instability-high (MSI-H) tumors. We present data on antitumor immunity with pembrolizumab in pts from the phase 2, KEYNOTE-164 study who had approximately 3 years of follow-up, and in pts re-treated after disease progression. Methods: KEYNOTE-164 enrolled pts with metastatic MSI-H CRC, MSI-H status confirmed locally by IHC or PCR, and ≥2 (cohort A) or ≥1 (cohort B) prior lines of therapy (fluoropyrimidine, oxaliplatin, irinotecan, or anti VEGF/EGFR). Eligible pts received pembrolizumab 200 mg Q3W for 2y (35 administrations) or until progression, unacceptable toxicity, or withdrawal. Pts who stopped pembro due to a confirmed CR or after completing 2y of treatment and who progressed after stopping were eligible for re-treatment with up to 17 administrations in the second-course phase, at investigator discretion. Tumor response was assessed Q9W per RECIST v1.1 by independent review. The primary endpoint was ORR. Secondary endpoints included DOR, PFS, OS, and safety. The data cutoff date was Sep 9, 2019. Results: At data cutoff, the median follow-up was 31.4 mo (range, 0.2-47.8) for 61 pts in cohort A and 36.1 mo (0.1-39.3) for 63 pts in cohort B. ORR was 32.8% (3CR, 17PR; 95% CI% 21.3-46.0) for cohort A and 34.9% (8CR, 14PR; 95% CI 23.3-48.0) in cohort B. Median DOR was not reached (NR [range, 6.2-41.3+]) and not reached (range, 3.9+ to 37.1+), respectively. Fifteen pts in cohort A and 17 in cohort B had ongoing responses at data cutoff. Median PFS was 2.3 mo (95% CI 2.1-8.1) with 3-yr PFS rate of 31% in cohort A and was 4.1 mo (2.1-18.9) with 3-yr PFS rate of 34% in cohort B. Median OS was 31.4 mo (21.4-NR) with 3-yr OS rate of 49% in cohort A and was not reached (19.2-NR) with 3-yr OS rate of 52% in cohort B. Nine pts (6 in cohort A, 3 in cohort B) had a second course of treatment. The best response in second course was PR in 1 patient each in cohort A and B. Grade 3-4 drug-related adverse events occurred in 10 (16%) pts in cohort A and 8 (13%) pts in cohort B. No grade 5 drug-related events occurred. Conclusions: After approximately 3 y of follow-up, pembrolizumab continues to provide effective long-term antitumor immunity with durable responses, with small numbers of drug-related adverse events and no drug-related deaths in pts with advanced, MSI-H CRC. Clinical trial information: NCT02460198 .
Trifluridine/tipiracil or regorafenib in refractory metastatic colorectal cancer patients: An AGEO prospective “real life” study.
Authors: Coutzac Clélia , Trouilloud Isabelle , Artru Pascal , Henriques Julie , Masson Thérese , De La Fouchardiere Christelle , Doat Solene , Bouché Olivier , Coriat Romain , Saint Angelique , Moulin Valérie , Vernerey Dewi , Tougeron David , Taieb Julien 
Published: May 2020

4036 Background: Regorafenib (R) and trifluridine/tipiracil (T) have proved their efficacy in patients (pts) with metastatic colorectal cancer (mCRC) refractory to standard chemotherapy and targeted therapies. However, it remains unclear which drug should be administered first. Methods: This observational study was prospectively conducted in 13 centers between 6/2017 and 9/2019 in France. All consecutive pts with chemoresistant mCRC and receiving T and/or R were eligible. The aim of this study was to describe efficacy and tolerability of T and/or R. Overall survival (OS) and progression-free survival (PFS) of pts receiving T then R (T/R) and the opposite sequence (R/T) were also assessed. Results: A total of 237 pts (25% R and 75% T) were enrolled (109 male, median age: 67 years (32-91), mean previous lines of treatment: 2.5 (1-7)). Baseline ECOG PS was 0-1 in 77% of pts. As compared to R pts, T pts were significantly older (68 years vs 63; p = 0.033) and with > 3 metastatic sites (44% vs 30%, p = 0.018). Median OS were 6.6 and 6.2. months in the T and R group, respectively (NS). Median PFS were 2.4 and 2.1 months in the T and R group, respectively (NS). After matching 46 paired pts according to primary tumor resection, age and number of metastatic sites, a trend to a longer OS (9.5 vs 6.8 months; p = 0.17) and a significantly longer PFS (2.8 vs 2 months; p = 0.048) were observed in the T group. Among the overall population, 24% of pts received R/T or T/R sequence. Median OS from first treatment were 10.7 months in the R/T group and 9.8 months in the T/R (NS). Treatment sequence was not an independent prognostic factor for OS or PFS in multivariable analysis. Tolerability profiles were similar to previously published data, but dose reductions were more frequent in the R group (44 vs 27%, p = 0.008). Conclusions: Efficacy and safety results in this real life prospective study are in line with those published phase III trials. Both treatments seem similar in term of efficacy favoring T for clinical use as shown by the higher number of patients receiving this drug.
Rectal cancer in young patients: Clinicoepidemiologic profile and treatment outcomes.
Authors: Goyal Pankaj. , Maheshwari Udip , Jain Parveen , Agrawal Chaturbhuj , Chaudhari Krushna A. , Goyal Sumit , Batra Ullas , Bothra Sneha J , Goel Varun , Talwar Vineet , Doval DC 
Published: May 2020

4042 Background: Colorectal cancers are 3rd most common cause of cancer globally however studies of rectal cancers alone in younger patients are scarce. Rectal cancers in Asian patients present at a younger age and has an aggressive tumor biology. This study looks at rectal cancer in young patients, ≤30 years old, with the aim to report clinico-epidemiologic profile and treatment outcomes in this subgroup. Methods: Retrospective analysis was conducted at a tertiary care centre. Of total 845 rectal cancer patients between 2012-2017, 103 patients of young rectal cancers were enrolled. Kaplan Meier method was used for survival analysis and cox regression analysis was done to identify factors affecting survival. Results: Young rectal cancer patients constituted 12.2% of the total rectal cancer patients. Male: Female ratio was 2.3:1 and the mean age was 24.7 ± 3.9 years. Around 73.8 % patients had locoregional disease (stage I/II/III) at presentation.CEA levels were elevated in 36.9% of patients, while most common histology was signet ring cell histology which was present in 51.5% of patients. Of 76 patients with locoregional disease, 75% received neoadjuvant chemoradiotherapy, 7.9% received neoadjuvant chemotherapy alone while 3.9% received neoadjuvant radiotherapy alone. Of 76 patients with locoregional disease, 55 patients underwent surgery of which 53.9% underwent low anterior resection while 18.4% underwent abdomino-perineal resection. Pathologic CR rates were seen in 13.3%, while recurrences were seen in 55.4% of non-metastatic patients. Overall 5-year survival for the whole study group was 19.5%, while 1-year PFS and 3-year DFS for metastatic and non-metastatic disease were 5% and 43.8% respectively. On regression analysis elevated CEA levels and not achieving a pathologic CR (pCR) with neoadjuvant therapy had a trend towards worse overall survival (HR 2, 95% CI 1-4, p = 0.063), (HR 4.7, 95% CI 0.64-35.1, p = 0.125) respectively. Conclusions: Rectal cancers in Asia present at younger age and this younger population is associated with advanced stage, increased CEA at presentation, aggressive histology and poor survival. CEA raise and not achieving pCR were associated with trend towards worse survival.
Characterization of sociodemographic and clinicopathological features and associated outcomes of patients (Pts) with anal squamous cell cancer (ASCC): Analysis of 44,084 pts in the National Cancer Database (NCDB).
Authors: Young Joanna Alyse , Trufan Sally Jeanne , Worrilow William Mills , Musselwhite Laura W. , Nazemzadeh Reza , Kadakia Kunal C. , Chai Seungjean , Salmon John Stuart , Hwang Jimmy J. , Kim Edward S. , Raghavan Derek , Salem Mohamed E. 
Published: May 2020

4052 Background: ASCC incidence is rising. There are limited data on the relationships between sociodemographic & clinicopathological features and outcomes of ASCC pts. Methods: Pts diagnosed with ASCC between 2004 and 2016 were retrospectively reviewed. Data obtained from the NCDB were used to examine the impact of sociodemographic status on clinicopathological features and outcomes. Pts were categorized based on low (median < $38,000) or high (≥$68,000) income and low ( > 21% with no high school diploma) or high ( < 7% with no high school diploma) education areas based on zip code at time of diagnosis. Logistic regression and chi-square were used to examine differences between groups. Results: In total, 44,084 pts with ASCC were identified: median age, 59 yrs, 86% white; 11% black; 64% female. Most pts (84%) resided in metro areas; 29.7% vs 19.8% lived in high vs low income areas; 22.9% vs 17.8% lived in high vs low education areas. Seven percent were uninsured, 50% had government (Gov), and 43% had private insurance. Male gender (HR 1.62, CI 1.41-1.85, p < 0.001), low income area (HR 1.28, CI 1.19-1.37, p = 0.014), and insurance status (Gov, HR 1.55, CI 1.32-1.82, p < 0.001 and uninsured, HR 1.37, CI 1.37-1.85, p = 0.039) were associated with a higher risk of death. After adjusting for age, sex, race, stage, grade, insurance status, and comorbidity, pts from low income/education (n = 6695) vs high income/education (n = 4316) areas had a 33 % increased risk of death (HR: 1.33, p < 0.001). Pts with stage IV ASCC in the low income/education (n = 227) vs high income/education (n = 295) groups had worse overall survival (mOS, 1.4 vs 1.9 yrs, p < 0.020). Of the 44,084 pts, 5461 (12.4%) had confirmed HPV status. Of these, 2658 (48.7%) were HPV+ (high risk subtypes) and 2803 (51.3%) were HPV-. Compared to the HPV- pts, HPV+ pts were more likely to be women (71.8% vs 67.8%, p = 0.001), have stage 3 (38.1% vs 33.6%) or 4 (7.9% vs 5.9%, p < 0.001) cancer, and have poorly differentiated (29.5% vs 25.6%, p < 0.001) tumors. There were no significant differences in race, education, income, metro area, insurance status, or comorbidity between the HPV+ and HPV- pts. Moreover, HPV status did not impact OS (HR 0.92, CI 0.81-1.04, p = 0.195). Conclusions: HPV status was not correlated to income, education or insurance status, and did not impact OS in ASCC pts. Male gender and insurance status were associated with increased risk of death. Pts living in low income and low education areas were associated with worse survival.
PDL1 expression predicts therapeutic outcome in non metastatic anal squamous cell carcinoma (NMASCC).
Authors: Iseas Ilma Soledad , Golubicki Mariano , Robbio Juan , Ruiz Gonzalo , Salanova Ruben , Mariani Javier , Slutsky Ezequiel , Vecchioni Daniela , Oviedo Ana , Guerra Florencia , Maquieira Julian , Basilletti Jorge , Picconi Alejandra , Roca Enrique , Mendez Guillermo , Coraglio Mariana 
Published: May 2020

4054 Background: NMASCC is a rising incidence disease with up to 30% of treatment failure to achieve complete response (CR) after standard chemoradiotherapy (CRT) leading to severe morbidity and death. Stage III-TNM, p53 mutations, HPV negativity, HIV infection are linked to treatment failure. We investigated the predictive/prognostic role of TNM, CR, HPV, PDL1 positivity and CD3/CD8 densities in NM-ASCC from a single institution. Methods: All 79 eligible consecutive NMASCC pts (available FFPE pre-treatment samples) seen from October-2009 to April-2019 having completed definitive CRT (50.4 Gy Pelvic Radiotherapy with Mitomycin-C 12mg/m2/IV/d1-5 / FU 1000mg/m2/d1-4 d29-32 (28%), Mitomycin-C/Capecitabine 825 mg/m2/bid (38%), Cisplatin 60 mg/m2/IV d1-29 and 5FU (34%) were analyzed. Mean age: 59 (range 26-87), 72% female, Stage III: 59%, HPV positive: 86% (HPV-16: 80%);14% HIV positive. IHC assessed by two pathologist for PD-L1 expression (ClonSP263) and CD3-CD8+ TILS densities (Clone 2GV6, Clone SP57). HPV-DNA assessed by PCR (BSGP5+/6+ multiplexed with beta-globin). Kaplan-Meier survival, CR, DFS, OS and Univariate analyses were performed using Cox proportional hazard model. Results: CR achieved within 6 months of treatment completion was 68%( 53pts). Median follow-up after treatment completion: 35 months (range 6 –149). As of February 2020, 82% (65 pts) are alive, no evidence of disease:(57%) 46 pts, recurrence rate: 26%(22 pts), cancer death: 18% (14 pts). PDL1+ tumors ( > 1% positivity-CPS score): 56%, expression levels: 1-5% (57%,26p), > 10%-100% (43%,19p). PDL1+ had a strong association with CR (p = 0.021); higher PDL1+ levels had 8-fold of CR-likelihood than PDL1 negative.(OR 8.50 vs. 1.12). Significative Spearman correlation between PDL1 tumors with CR and CD3-CD8 TILS density was observed (R = 0.43,p = 0.0017 and R = 0.36,p = 0.00094 respectively), albeit CD3-CD8 failed to reach significance as prognostic factors for either CR, DFS or OS. Only CR and PDL1 positive were strongly significantly associated to DFS (HR 0.10 [IC 95% 0.04-0.28] p < 0.001 and HR 0.28 [IC 95% 0.11-0.73] p = 0.006) and OS (HR 0.12 [IC 95% 0.03-0.45] p < 0.001 and HR 0.15 [IC 95% 0.03-0.68] p < 0.004). Low prevalence of HPV negative, early tumors, HIV positive cases in our series probably impacted in statistical power for prognosis correlation. Conclusions: PDL1 positivity was the strongest predictive/prognostic factor in NM-ASCC. Alternative therapeutics options to standard CRT should be explored on poor-risk patients as HPV-negative, P53-mutated and PDL1 negative patients.
Impact of tumor side on clinical outcomes in stage II and III colon cancer with known microsatellite instability status.
Authors: Zakka Katerina Mary , Williamson Shayla , Jiang Renjian , Alese Olatunji B. , Shaib Walid Labib , Wu Christina , Behera Madhusmita , El-Rayes Bassel F. , Akce Mehmet 
Published: May 2020

4068 Background: Microsatellite instability high (MSI-H) status indicates better prognosis in early stage colon cancer (CC) compared to microsatellite stable (MSS). However, the impact of tumor side, left side (L) versus right side (R), is not described on clinical outcomes based on MSI status. Methods: Patients with pathological stage II and III primary adenocarcinoma of the colon between 2010 and 2015 were identified in the National Cancer Database (NCDB) using ICD-O-3 morphology and topography codes: 8140-47, 8210-11, 8220-21, 8260-63, 8480-81, 8490 and C18.0, 18.2,18.3, 18.5,18.6, 18.7. Univariate (UVA) and multivariable (MVA) survival analyses were conducted, and Kaplan-Meier Curves were used to compare overall survival (OS) based on tumor location and treatment received with Log-rank test. Results: A total of 35,071 patients with stage II (n = 17,629) and III (n = 17,442) CC were identified. 51.3% female; 81.5% Caucasian; median age 66 (range, 18-90). Majority of stage II and III tumors were R, 61.2% (n = 10,794) and 56.0% (n = 9,763). MSI-H was more common in stage II compared to III, 23.3% (n = 4,115) vs 18.2% (n = 3,171) (p < 0.0001). Survival was better in stage II MSI-H compared to MSS, 5 year-OS 75.1% vs 71.8% (p = 0.0057). However, stage III CC survival was better in MSS compared to MSI-H, 5-year OS 60.5% vs 58.0% (p < 0.001). In stage II MSI-H CC R was more common than left, 78.3 % (n = 3223) vs 21.7% (n = 892). There was no significant difference in survival between stage II MSI-H L vs R (5-year OS 76.2% vs 74.7%, p = 0.1578). Stage II MSS CC R was more common than L, 56.0% (n = 7571) vs 44.0% (n = 5943), and survival was better in L vs R (5-year OS 73.2% vs 70.8%, p = 0.0029). Stage III MSI-H CC was more common in R than L, 75.6% (n = 2397) vs 24.4% (n = 774) and survival was better in L (5-year OS 62.5% vs 56.5%, p = 0.0026). Stage III MSS CC was more common in R than L, 51.6% (n = 7366) vs 48.4% (n = 6905), and survival was better in L vs R (5-year OS 67.0% vs 54.4%, p < 0.001). Conclusions: Survival was better in left sided tumors compared to right in stage II MSS, stage III MSS and stage III MSI-H CC.
Translational research of voltage-A1: Efficacy predictors of preoperative chemoradiotherapy and subsequent nivolumab monotherapy in patients with microsatellite-stable locally advanced rectal cancer.
Authors: Inamori Koji , Togashi Yosuke , Bando Hideaki , Tsukada Yuichiro , Suzuki Ayako , Suzuki Yutaka , Kotani Daisuke , Fukuoka Shota , Kojima Motohiro , Fukui Makoto , Yuki Satoshi , Komatsu Yoshito , Homma Shigenori , Uemura Mamoru , Kato Takeshi , Ito Masaaki , Nishikawa Hiroyoshi , Yoshino Takayuki 
Published: May 2020

4073 Background: In VOLTAGE-A1, after 5 cycles of nivolumab (240 mg q2 weeks) plus radical surgery following chemoradiotherapy (CRT; 50.4 Gy with capecitabine 1,650 mg/m2), a major pathologic response is observed in 38% (AJCC tumor regression grade 0-1) of 37 patients with microsatellite-stable locally advanced primary rectal cancer. Here, biomarkers for predicting the efficacy of this treatment were investigated. Methods: Serial tumor biopsies and blood collections were performed at 4 time points; before CRT, after CRT, after 3 cycles of nivolumab, and before surgery. Tumor-infiltrating lymphocytes (TILs) and DNA/RNA were extracted from tumor samples, and peripheral blood mononuclear cells (PBMCs) were extracted from blood samples. We analyzed the immune status of the patients by flow cytometry using the collected TILs and PBMCs. Whole exome and RNA sequencing analyses were conducted using the extracted DNA and RNA, respectively. The PD-L1 status of tumor samples was also evaluated by in vitro diagnostic immunohistochemistry staining. Results: Among the 24 patients whose samples were serially collected, 11 (46%) were AJCC grade 0-1 and 13 were 2-3. Before CRT, effector regulatory T (eTreg) cells in TILs were higher in patients with AJCC grade 2-3, and both the CD8+ T cell/eTreg cell ratio in TILs and PD-L1-positive tumor cells (≥1%) were higher in patients with AJCC grade 0-1 (p = 0.047, p = 0.083, respectively). Ki67 expression by CD8+ T cells in TILs was higher before CRT in patients with AJCC grade 0-1 (p = 0.037) and increased after CRT in all patients. Patients with consensus molecular subtype (CMS) 1 and CMS3 achieved AJCC grade 0-1 at rates of 100% (2/2) and 60% (4/6), respectively. In contrast, patients with CMS2 and CMS4 achieved AJCC grade 0-1 at rates of 43% (3/7) and 29% (2/7), respectively. The tumor mutation burden of pre-CRT samples was significantly higher in patients with AJCC grade 0-1 (median 1.45/MB) than in patients with AJCC grade 2-3 (0.84/MB) (p = 0.016). Conclusions: A higher CD8+ T cell/eTreg cell ratio, PD-L1-positive, Ki67 expression by CD8+ T cells in TILs, CMS1 or 3, and higher tumor mutation burden are good predictors of the efficacy of the sequential combination of CRT and nivolumab. Further results will be reported in the meeting. Clinical trial information: NCT02948348 .