bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of a computational decision support system for molecularly targeted treatment planning by the clinical outcome data of the randomized trial SHIVA01.
Authors: Dirner Anna , Doczi Robert , Filotas Peter , Vodicska Barbara , Varkondi Edit , Tihanyi Dora , Dupain Célia , Servant Nicolas , Kamal Maud , Hegedűs Csilla , Schwab Richárd , Le Tourneau Christophe , Valyi-Nagy Istvan T. , Peták István 
Published: May 2020

3642 Background: Precision oncology requires the identification of individual molecular pathomechanisms to find optimal personalized treatment strategies for every cancer patient. Incorporation of complex molecular information into routine clinical practice remains a significant challenge due to the lack of a reproducible, standardized process of clinical decision making. Methods: To provide a standardized process for molecular interpretation, we develop a precision oncology decision support system, the Realtime Oncology Molecular Treatment Calculator (MTC). MTC is a rule-based medical knowledge engine that dynamically aggregates and ranks relevant scientific and clinical evidence using currently 26,000 evidence-based associations and reproducible algorithm scoring of drivers, molecular targets to match molecular alterations to efficient therapies. To validate this novel method and system, we used data of the SHIVA01 trial of molecularly targeted therapy (Lancet Oncol 2015 16:1324-34). Molecular profiles of participants were uploaded to MTC and aggregated evidence level (AEL) values of associated targeted treatments were calculated, including those used in the SHIVA01 trial. Results: The MTC output provided a prioritized list of drugs associated with the driver alterations in the patient molecular profile, where ranking is based on AEL values. Of 113 patients who received targeted therapy with available clinical best response data, disease control was experienced in 63 cases (PR: 5, SD: 58), while disease progression occurred in 50 cases. The average AEL score for the therapies applied was significantly higher in the responsive group than in the non-responsive group (1512 and 614, respectively (p = 0.049)). In 94 cases, drugs other than those used for therapy were ranked higher by the MTC. The average AEL difference between the top-ranked and the used drugs was in an inverse correlation with clinical response, i.e. smaller differences associated with a better outcome. Conclusions: Results indicate that the aggregation of evidence-based tumor-driver-target-drug associations using standardized mathematical algorithms of this computational tool is a promising novel approach to improve clinical decisions in precision oncology. Further validation based on the results of other targeted clinical trials and real-life data using more detailed molecular profiles is warranted to explore the full clinical potential of this novel medical solution.
Encorafenib plus cetuximab with or without binimetinib for BRAF V600E metastatic colorectal cancer: Updated survival results from a randomized, three-arm, phase III study versus choice of either irinotecan or FOLFIRI plus cetuximab (BEACON CRC).
Authors: Kopetz Scott , Grothey Axel , Van Cutsem Eric , Yaeger Rona , Wasan Harpreet Singh , Yoshino Takayuki , Desai Jayesh , Ciardiello Fortunato , Loupakis Fotios , Hong Yong Sang , Steeghs Neeltje , Guren Tormod Kyrre , Arkenau Hendrik-Tobias , Garcia-Alfonso Pilar , Gollerkeri Ashwin , Maharry Kati , Christy-Bittel Janna , Tabernero Josep 
Published: May 2020

4001 Background: BEACON CRC is a randomized, phase 3 study which evaluated the triplet of encorafenib (ENCO) + binimetinib (BINI) + cetuximab (CETUX) and the doublet of ENCO + CETUX vs. investigator’s choice of irinotecan + CETUX or FOLFIRI + CETUX in patients (pts) with BRAFV600E metastatic colorectal cancer (mCRC) whose disease had progressed after 1-2 prior regimens in the metastatic setting. Primary endpoints were overall survival (OS) and objective response rate (ORR; by blinded central review) for triplet vs control. In a previous interim analysis, triplet and doublet improved OS and ORR versus standard of care. Here we report on an updated analysis. Methods: Updated analysis includes 6 months of additional follow-up and response data for all randomized pts. The study is ongoing. Results: Pts received triplet (n=224), doublet (n=220), or control (n=221). Median OS was 9.3 months (95% confidence interval [CI]:8.2, 10.8) for triplet and 5.9 months (95% CI:5.1-7.1) for control (hazard ratio [HR] (95% CI): 0.60 (0.47-0.75)). Median OS for doublet was 9.3 months (95% CI: 8.0-11.3) (HR vs. control: 0.61 (0.48-0.77). Confirmed ORR was 26.8% (95% CI: 21.1%-33.1%) for triplet, 19.5% (95% CI: 14.5%-25.4%) for doublet, and 1.8% (95% CI: 0.5%-4.6%) for control. Retrospective subgroup analyses suggested some pts may benefit more from triplet than doublet therapy (Table). Both triplet and doublet showed improved OS compared to control in all subgroups. Adverse events were consistent with prior analysis, with grade ≥3 adverse events in 65.8%, 57.4%, and 64.2% for triplet, doublet and control, respectively. Conclusions: The updated analysis of the BEACON CRC study confirmed that encorafenib + cetuximab with or without binimetinib improved OS and ORR in previously treated pts with BRAF V600E mCRC compared with standard chemotherapy. Clinical trial information: NCT02928224 . [Table: see text]
Preliminary results of the organ preservation of rectal adenocarcinoma (OPRA) trial.
Authors: Garcia-Aguilar Julio , Patil Sujata , Kim Jin K. , Yuval Jonathan B. , Thompson Hannah , Verheij Floris , Lee Meghan , Saltz Leonard B. ,   on behalf of the OPRA Consortium
Published: May 2020

4008 Background: Organ preservation (OP) with a watch and wait strategy (WW) and total neoadjuvant therapy (TNT) are new treatment paradigms for patients with locally advanced rectal cancer. The safety and efficacy of WW and of TNT have not been studied prospectively. Methods: Patients with MRI stage II and III rectal adenocarcinoma were randomized to 4 months of FOLFOX or CAPEOX before (Induction) or after (Consolidation) fluorouracil or capecitabine based chemoradiotherapy (CRT). Patients were re-staged 8-12 weeks after finishing TNT with digital rectal exam, flexible sigmoidoscopy and MRI. Patients with complete or near-complete clinical response were offered WW. Those with incomplete response had total mesorectal excision. The trial was designed so that each arm served as its own single-stage study that discriminates between 3-year disease-free survival (DFS) rates of 75% (historical null) and 85%, with 86% power, and a two-sided type I error of 5%. Secondary objectives included comparing DFS, OP, and distant metastasis-free survival (DMFS) rates between the two arms using the log-rank test. Results: Of 324 patients enrolled, 307 (152 I, 155 C) are currently evaluable for the time-to-event analysis as of 2/1/2020. Median follow-up is 2.1 years; 52 DFS events were observed. Patient demographics and tumor characteristics were generally balanced across the two arms. Full compliance with systemic chemotherapy was 82% and 81% for the I- and C-arms, respectively. The median radiation dose was 5400 cGy for both arms. Table shows 3-y DFS, DMFS, and OP rates. Conclusions: A WW strategy for patients with locally advanced rectal cancer that achieve a clinical complete response to TNT results in organ preservation for a high proportion of patients without compromising survival. Up-front CRT followed by consolidation chemotherapy resulted in a numerically higher WW rate compared to induction chemotherapy followed by CRT. Clinical trial information: NCT02008656 . [Table: see text]
A new prognostic and predictive tool to enhance shared decision making in stage III colon cancer.
Authors: Sobrero Alberto F. , Puccini Alberto , Shi Qian , Grothey Axel , Andre Thierry , Shields Anthony Frank , Ceppi Marcello , Bruzzi Paolo 
Published: May 2020

4010 Background: Survival outcomes in patients with stage III colon cancer varies widely according to T-N sub-stages. The ability to estimate the benefit of each therapeutic option (surgery alone, fluoropyrimidines alone, oxaliplatin-based doublet for either 3 or 6 months) in each T-N subgroup within stage III, may provide more accurate information helping doctors and patients in the complex shared decision-making process surrounding adjuvant therapy. Methods: Theoutcomedata of 12,834 patients with stage III colon cancer enrolled in the IDEA trial served as our database. Patients were categorized in 16 sub-stages, based on the T-N categories. We created a meta-regression model to predict the expected 3-year DFS within each T-N sub-stage and hence the 5-year DFS rates were projected. We then evaluated the efficacy of each therapeutic option in every sub-stage, working backward by subtraction, using an average of the HRs reported in the pertinent trials publication as conversion factor. Results: Large differences in 3-year DFS rate were observed among the subgroups, ranging from 95% (T1N1a) to 29% (T4N2b) in the overall population. The contribution to outcome of each therapeutic option in this setting varied widely across sub-stages. According to our model, patients with T1N1a cancers have a projected 5-year DFS of 85% with surgery alone. Adjuvant fluoropyrimidine alone results in 4.2% absolute DFS gain; an additional 1.7% and 0.6% gain is seen with oxaliplatin for 3 and 6 months, respectively. Patients with T4N2b cancers show a 4.7% 5-year DFS with surgery alone, and a 7.1%, 5.0%, 2.1% increase with the aforementioned adjuvant options, respectively. Conclusions: The resulting overlay bar graph gives patients and doctors the projected relative benefit of each treatment option and may substantially help the shared decision-making process.
Impact of empirically eliminating 5-fluorouracil (5-FU) bolus and leucovorin (LV) in patients with metastatic colorectal cancer (mCRC) receiving first-line treatment with mFOLFOX6.
Authors: Basilio Alexa , Shah Anand , Sommerer Katelyn , Chehab Sarah , Bottiglieri Salvatore Michael , Imanirad Iman 
Published: May 2020

4022 Background: Systemic chemotherapy with a 5-FU-based regimen, such as mFOLFOX6, is the preferred first line treatment option for mCRC. Due to hematologic toxicities associated with the 5-FU bolus component, providers may choose to eliminate it empirically in patients receiving palliative therapy. This study aimed to assess the impact of empirically eliminating the 5-FU bolus and LV from first line treatment with mFOLFOX6 in mCRC. Methods: This was a retrospective chart review of patients ≥ 18 years old with mCRC receiving palliative first line mFOLFOX6 chemotherapy with (bolus) or without (non-bolus) the 5-FU bolus and LV components from January 1, 2015 through August 31, 2019 at Moffitt Cancer Center. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), disease control rate (DCR) defined as partial response and stable disease at first scan, utilization of growth factor support and safety. Results: Data analysis cutoff was December 31, 2019, with 61 patients included in the bolus arm and 72 in the non-bolus arm. Median follow-up time was 21.8 months. No difference was found in median PFS (8.12 vs. 6.64 months, p=0.787) or OS (29.36 vs. 21.6 months, p=0.395) between the bolus and non-bolus arms, respectively. Observed DCR at first scan was similar between both arms (47.3% vs. 52.7%, p=0.44). Utilization of growth factor support was significantly higher in the bolus arm (73.7% vs. 26.3%, p=0.012). Fewer grade ≥ 3 treatment-related hematologic adverse events (AE) were seen in the non-bolus arm (37.7% vs. 22.2%, p=0.058) (table). Conclusions: This is the only study to date that analyzed the impact of empirically eliminating 5-FU bolus and LV from first line palliative therapy with mFOLFOX6 in mCRC. Results showed no significant difference in median PFS or OS. Despite reduced growth factor utilization, the non-bolus arm demonstrated a favorable safety profile with less treatment-related hematologic grade ≥ 3 AE. The results of this study warrant consideration of empirically eliminating 5-FU bolus and LV from the mFOLFOX6 regimen to avoid additive toxicities without negatively impacting efficacy. [Table: see text]
Differential association of proton pump inhibitors with efficacy of capecitabine and 5-fluorouracil in metastatic colorectal cancer: A post-hoc analysis from AXEPT phase III trial.
Authors: Kim Sun Young , Lee Ji Sung , Kang Junho , Morita Satoshi , Park Young Suk , Sakamoto Junichi , Muro Kei , Xu Rui-hua , Kim Tae Won 
Published: May 2020

4023 Background: Proton pump inhibitors (PPIs) reportedly can impair the absorption of oral anticancer agents by potent acid suppression. Concomitant use of a PPI with capecitabine (Cap) was suggested to be associated with poor outcome in gastrointestinal cancers, however, the potential interaction has not been studied yet in a prospective randomized clinical trial comparing Cap with 5-fluorouracil (FU). We analyzed the differential impact of PPI use on Cap and FU using dataset from AXEPT trial, a phase III randomized trial that demonstrated non-inferiority of a modified XELIRI (mXELIRI; Cap plus irinotecan) with FOLFIRI (FU, leucovorin and irinotecan), both either with or without bevacizumab in patients (pts) with metastatic colorectal cancer (mCRC). Methods: From the per-protocol set (n = 620), pts with available information on concomitant medications (n = 482) were eligible for this sub-study. PPI use was defined as concomitant exposure of Cap and any PPI for 20% or more of the study period. The treatment-by-PPI-use interaction was examined adjusting to stratification factors including age, sex, country, performance status, number of metastatic sites, previous use of oxaliplatin, and concurrent bevacizumab treatment. Results: 49 (10.1%) pts were PPI users. Clinical characteristics were well balanced between the two groups differing in PPI use. In PPI users, the mXELIRI group tended to have poorer OS (hazard ratio [HR], 1.83; 95% confidence interval [CI], 0.96–3.48; p = 0.0644) compared with the FOLFIRI group. In contrast, within PPI non-users, OS of mXELIRI was better than that of FOLFIRI (HR, 0.76; 95% CI, 0.61- 0.95; p = 0.0162). Similarly, a trend of worse PFS with mXELIRI than with FOLFIRI was observed in PPI users (HR, 1.73; 95% CI, 0.94-3.21; p = 0.0798), but not in PPI non-users (HR, 0.90; 95%CI, 0.73 – 1.10; p = 0.2871). Treatment-by-PPI-use interaction was significant for OS (p = 0.0116) and PFS (p = 0.0415). No significant interactions were found between treatment and PPI use in terms of treatment failure, overall response, disease control, and grade 3–4 toxicities. Conclusions: There was a significant interaction between PPI use and treatment (Cap vs FU) in terms of OS and PFS in AXEPT dataset. This suggests that PPI use could impair the efficacy of Cap, but not that of FU. PPIs should be used with caution in pts with mCRC taking Cap. Clinical trial information: NCT01996306 .
Skeletal muscle loss under chemotherapy and its association with survival and systemic treatment toxicity in metastatic colorectal cancer: An AGEO prospective multicenter study.
Authors: Gallois Claire , Bourillon Camille , Auclin Edouard , Artru Pascal , Lievre Astrid , Lecomte Thierry , Locher Christophe , Marthey Lysiane , Faroux Roger , Pernot Simon , Barret Maximilien , Taieb Julien 
Published: May 2020

4025 Background: We showed in a previous work that “Patient Generated-Subjective Global Assessment” (PG-SGA) was independently associated with survival and treatment toxicities in non-pretreated metastatic colorectal cancer (mCRC) patients. We have evaluated here if muscle mass in these patients can provide useful additional information for clinical practice. The objective of the present work was to evaluate the association between baseline sarcopenia, and the variation of the Skeletal Muscle Index (SMI) under treatment with survival and chemotherapy-related toxicities in our population of non-pretreated mCRC patients. Methods: This prospective multicenter observational study enrolled non-pretreated mCRC patients. Measurement of SMI was performed on routine CT scan at day 0 (D0) and day 60 (D60). PG-SGA score and other nutritional factors were collected at D0. Progression-free survival (PFS) and overall survival (OS) were calculated from treatment start. Treatment related toxicities were registered according to the NCI CTCAE v4.0. Results: 149 patients were included in eight French centers from 7/2013 to 11/2016. Sarcopenia at baseline was not significantly associated with survival outcomes or chemotherapy-related toxicities. The best cut-point value of SMI variation (between D0 and D60) for OS prediction obtained with a log-rank maximisation method was -14%. The decrease in SMI > 14%, with a median follow-up of 23 months, was significantly associated with shorter PFS (6 vs 9 mo; HR 1.8, 95%CI 1.1-3.1, p = 0.02) and OS (8.5 vs 26 mo; HR 2.4, 95%CI 1.3-4.4, p = 0.004), independently of hypoalbuminemia and malnutrition defined by PG-SGA, in multivariate analysis. 40% of patients with a SMI decrease > 14%, and 22% of patients with a SMI increase or stable or decrease < 14% developed grade ≥ 2 clinical toxicities (OR 3.0, 95%CI 1.2-7.7, p = 0.02), but the difference was not statistically significant in multivariate analysis (OR 2.3. 95%CI 0.8-6.7, p = 0.1). Conclusions: To our knowledge, this study is the first study assessing the association of skeletal muscle loss with survival and treatment toxicities in patients with mCRC prospectively. In our population of non pre-treated mCRC patients, baseline sarcopenia was not associated with poor survival outcomes, but the decrease in SMI > 14% during the first two months of treatment was significantly associated with decreased PFS and OS, independently of other prognostic and nutritional factors.
Prognostic characteristics of patients with benign mesenteric lymph node enlargement after surgical resection for colorectal cancer.
Authors: Tian Fei , Chen Gong 
Published: May 2020

4027 Background: Patients with lymph node metastasis of colorectal cancer (CRC) have a greater risk of recurrence. However, the characteristics of benign mesenteric lymph node enlargement (BLNE) are not well documented. The aim of this study is to assess clinical and prognostic significance of BLNE in patients with CRC. Methods: 601 patients who underwent surgery for stage 0, I, II CRC from January 2010 to April 2014 were included and separated into two groups by presence of BLNE. Univariate and multivariate analyses were constructed to demonstrate prognostic factors between BLNE group (n = 275) and control group (n = 326). Results: The risk of recurrence in BLNE group after curative resection was significantly lower than control group, with the 1-, 3-, and 5-year disease-free survival rates being 98.2, 91.6, and 86.9 %, in BLNE group and 95.7, 86.2, and 78.2 %, in control group respectively (p = 0.004). The mortality in BLNE group was lower compared with non BLNE group (mean overall survival: 95.7±1.2 vs. 89.5±1.4 months, p = 0.001). Patients of BLNE group also had a higher percentage of younger age, family tumor history, left sided tumors and tumor size ≥4cm. Adjusted Cox regression showed BLNE was an independent prognostic factor for both disease free survival and overall survival ( P= 0.003 and 0.001). Conclusions: The study indicates that BLNE can be a useful positive factor in predicting recurrence and long-term survival concerning CRC patients. This conclusion offers a new viewpoint about CRC genesis and progression.
Outcomes and prognostic factors of patients (pts) with metastatic colorectal cancer (mCRC) who underwent pulmonary metastasectomy (PM) with curative intent.
Authors: Gössling Gustavo Cartaxo de Lima , Pereira Fernando de Souza , Silva Rafaela Kathrine da , Andrade Leonardo de Brittes , Peruzzo Nicolas , Saueressig Maurício Guidi , Chedid Márcio Fernandes , Schwartsmann Gilberto , Parikh Aparna Raj 
Published: May 2020

4034 Background: Indications for PM in pts with mCRC are often based on the presence of favorable prognostic factors. We aimed to analyze the prognostic factors and outcomes of pts treated with PM for mCRC. Methods: We retrospectively identified pts with mCRC who underwent PM with curative intent between Jan 1985 and Dec 2019 at Hospital de Clínicas de Porto Alegre. Demographics, clinicopathological features and previously described prognostic factors were collected. Univariate Cox regression was performed and followed by Kaplan-Meier (KM) curves with log-rank test when significant. Results: Fifty-eight pts underwent PM. Demographics are described in Table. Wedge resection was performed in 87.9% and margins were negative in 89.1%. Mean number of lesions was 2.4 ± 1.7, with the largest measuring 1.7 ± 0.9 cm. Two or more resections were performed in 36.2%, nodal sampling in 27.3%, and nodal disease was found in 5.2%.Thirty-day readmission rate was 5.2%. One pt had a Clavien-Dindo grade IIIb complication. RAS/RAF/MMR and CK20/CDX2 were available for 13.8% and 58.6% of the sample. Median PFS 14 months (m) (95% CI 10.4 - 17.5), median OS 58 m (95% CI 33.5 - 82.4) and 5-year survival 49.8%. Unfavorable prognostic factors for OS included disease-free interval (DFI) < 24 m (40 m, 95% CI 31.8 - 48.1 vs 85 m, 95% CI 75.7 -96.2; P < 0.005), synchronous presentation (33 m, 95% CI 23.9 - 42.0 vs 77 m, 95% CI 50.7 - 103.2; P < 0.001), largest lesion size ≥ 2cm (37 m, 95% CI 22.9 - 51.0 m vs 81 m, 95% CI - 33.7 - 128.2, P = 0.019) and lack of CK20 expression (19 m, 95% CI 12.1 - 27.2 vs. 83 m, 95% CI 46.9 - 119.0; P < 0.001). More than one lesion at presentation was prognostic for PFS (11 m, 95% CI 7.6 - 14.3 vs 23 m, 95% CI 0.1 - 59.2; P = 0.003) but not OS (P = 0.11). Grade was significant at Cox regression but showed no effect in further analysis. Neither CEA at baseline or relapse, resection margins, Charlson comorbidity index (CCI) or adjuvant chemotherapy were prognostic. Conclusions: Our results suggest a benefit for select pts and PM. Lack of CK20 expression may be associated with more aggressive disease and shorter OS. Additional molecular prognostic factors after PM should be further explored. [Table: see text]