bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is adjuvant oxaliplatin (Ox) overutilized in colon cancer (CC): 408 cases from the practices of 102 oncologists.
Authors: Ziel Kathryn , Grothey Axel , Venook Alan Paul , Hussein Atif Mahmoud , Moss Jonathan , Love Neil 
Published: March 2020

e14564 Background: Recent long-term clinical trial follow-up suggests that adding Ox to a fluoropyrimidine (FP) may provide less benefit in adjuvant CC than originally believed (Tournigand JCO 2012). In addition, emerging data on tissue biomarkers such as microsatellite mismatch repair (MMR) and the 12-gene Recurrence Score (RS) suggest these assays may be helpful in better defining treatment benefit, and a new report provides evidence that RS may specifically predict the value of Ox (O'Connell ASCO 2012). In view of these developments we sought to document current use of adjuvant chemotherapy and physician perceptions about these decisions. Methods: U.S.-based oncologists were recruited to complete a survey and contribute treatment data for their last three patients (pts) with stage II disease and last pt with a stage III tumor. Results: 25 gastrointestinal cancer clinical investigators and 77 practicing oncologists participated, providing data from a total of 408 cases (92% treated since 2011). Findings from the two groups are similar and are presented in aggregate. A median of 9 and 15 pts annually were evaluated with Stage II and III tumors, respectively. Clinicians stated that they require a median of a 5% absolute reduction in relapse rate to use a FP alone and an additional 5% reduction to add Ox. Ox/FP was administered to 95 of 102 pts with stage III tumors (93%) and 85 of 306 pts with stage II disease (28%), particularly to those under age 70 or with T4 tumors (Table). MMR was evaluated in 127 pts (42%) with stage II and 20 pts (20%) with stage III disease. RS was obtained for 46 pts (15%) with stage II tumors, but only 2 pts (2%) with stage III. Conclusions: Adjuvant Ox is employed widely in spite of the fact that it may provide less benefit than many oncologists report requiring to initiate its use. However, several recent research developments may be laying the groundwork for a change in this treatment practice. [Table: see text]
Nodal status after preoperative chemoradiotherapy (CRT) in locally advanced rectal cancer: Prognostic evaluation of number of resected lymph nodes (LNs), metastatic resected LNs, and LN ratio in the National Cancer Institute of Brazil.
Authors: Vieira Fernando Meton , Araujo Rodrigo Otavio , Victorino Ana Paula , Oliveira Maria de Lourdes , Ferreira Carlos G. M. 
Published: March 2020

e14568 Background: For accurate colon cancer staging, 12 or more LNs must be resected. However, in rectal cancer, preoperative CRT can decrease the number of evaluable LNs, and the cutoff for a minimum number of LNs retrieved is unclear, as well as the prognostic value of LN ratio. Methods: We evaluated all locally advanced rectal cancer that received CRT followed by standard surgery (TME) from 2002 to 2009. External radiotherapy consisted of 45 to 50.4 Gy in 5 weeks and concomitant chemotherapy was bolus 5-Fu/LV. Pre-treatment staging included abdominal and pelvic CTs, chest RXs, CEA, and physical examination. Clinical data was collected from medical records and surgical specimens were pathologically evaluated accordingly to Quirke's method. LN ratio was defined as the ratio of the number of positive LN and total number of LN examined. Kaplan-Meier overall survival (OS) and disease free survival (DFS) curves were obtained and compared using the Long-rank test. Categorical variables were assessed using Fish's exact test. Results: Of 202 patients included, 125 (62%) were low rectal cancers (5cm or less from anal verge). Surgery was performed in a mean time interval from CRT of 3.95 months (0.28-24), and the type of resection was a low anterior resection in 139 (64%) and abdominoperineal resection in 63 (36%). Only 42.5% received postoperative chemoterapy. LN metastasis at the vascular stump level were more frequent in cancers lying more than 5 cm above the anal verge (p=0.02). Median number of LNs found in the specimens was 12 (0-56). The number of resected LNs had no impact in prognosis within the cutoff levels of 7 or 12, neither when considering only ypN0 cases. A LN Ratio >0.15 was found in 33% of our patients, and associated to a decrease in OS (p<0.001) and DFS (p=0.01), and was the only variable associated to distant metastasis (p=0.048). Conclusions: Positive LNs after CRT severely impaired prognosis in patients treated with rectal cancer. A prognostic cutoff value for LN dissection were not achieved, but a LN ratio >0.15 seems to be a strong predictor of recurrence and cancer related death.
Risk for developing brain metastases from colorectal cancer in long-term survivors with lung metastases and KRAS mutations.
Authors: Zoratto Federica , Loupakis Fotios , Cremolini Chiara , Salvatore Lisa , Schirripa Marta , Antoniotti Carlotta , Marmorino Federica , Campenni Giuseppe , Bergamo Francesca , Zagonel Vittorina , Lonardi Sara , Tomao Silverio , Cortesi Enrico , Allegrini Giacomo , Lucchesi Sara , Morvillo Manfredi , Savi Roberta , Marcucci Lorenzo , Minuti Gabriele , Falcone Alfredo 
Published: March 2020

e14574 Background: Brain metastases (BM) occur in 1-4% of metastatic colorectal cancer (mCRC) patients (pts). Retrospective series evidence that pts with a long survival from the diagnosis of mCRC are more frequently affected. Moreover, BM seem to be associated with lung metastases and KRAS activating mutations. The identification of clinical and molecular features correlated with BM may allow to define a subgroup more likely to develop BM, thus to benefit from neuroimaging follow up and early treatment. Methods: We prospectively tested the hypothesis that a higher incidence of BM occurs in a population of mCRC pts with a survival time from the diagnosis of mCRC ≥10 months, lung metastases and KRAS exons 2 and 3 mutations. Given a reported incidence of BM in unselected mCRC of around 3% (H0) and expecting an incidence in an “at risk” population selected on the basis of the 3 above reported features of 10% (H1), setting α and β errors to 0.05 and 0.10 respectively, we adopted the Fleming single-stage design for calculating the sample size of our analysis. The null hypothesis would have been rejected if at least 7 out of 104 “at risk” pts had developed BM. Results: 623 pts, enrolled in clinical trials treated with first-line chemotherapy and bevacizumab, were included in the overall study population in order to identify 105 (16.9%) pts who simultaneously had a survival time from the diagnosis of mCRC ≥10 months, lung metastases and KRAS exons 2 and 3 mutations. 26 (4.2%) out of 623 pts developed BM. 14 out 518 (2.7%) not “at risk” pts presented BM, while 12 out of 105 (11.4%) “at risk” pts did. The incidence of BM in the two groups differed significantly (Fisher’s exact test, p=0.0004). The null hypothesis was rejected according to the original design. Conclusions: This analysis confirms the hypothesis that the concomitant presence of the 3 analyzed risk factors increases the probability of developing BM in mCRC patients. Based on these data, the opportunity to consider a neuroimaging exam, such as brain CT scan or MRI, in this specific population might be taken into account in order to provide an early diagnosis of BM and therefore the most appropriate therapy in an asymptomatic phase.
Metronomic capecitabine (cape) and cyclophosphamide (CTX) for refractory metastatic colorectal cancer (mCRC): Results of a phase II trial.
Authors: Marmorino Federica , Cremolini Chiara , Loupakis Fotios , Salvatore Lisa , Schirripa Marta , Antoniotti Carlotta , Di Desidero Teresa , Canu Bastianina , Orlandi Paola , Fioravanti Anna , Masi Gianluca , Bocci Guido , Falcone Alfredo 
Published: March 2020

e14577 Background: The protracted exposure to low doses of cytotoxics according to metronomic schedules reported encouraging results in the treatment of different malignancies. In a recent trial from our group, the association of a single standard dose of CTX followed by metronomic UFT and CTX with celecoxib showed a very favourable safety profile and promising activity in a cohort of heavily pre-treated patients (pts) with gastrointestinal tumors (Allegrini, 2012). The aim of the present trial was to prospectively evaluate the activity of metronomic cape and CTX in a population of refractory mCRC pts. Methods: Pts with documented diagnosis of CRC, progressed during or within 3 mos from the last administration of standard therapies, were eligible. They received cape 800 mg PO bid and CTX 50 mg PO once daily. Treatment was administered continuously until disease progression. Primary endpoint was 2 mos-progression free rate (2m-PFR). Hypothesizing a 2m-PFR of 10% for refractory mCRC pts with no therapeutic options, metronomic cape plus CTX would have been judged promising for an estimated increase from 10 to 35% in 2m-PFR. According to the Fleming single-stage design, setting α and β errors 0.05 and 0.10, 25 evaluable pts were required. The null hypothesis would have been rejected if at least 6 pts were progression free at 2 mos. Results: Between June 2011 and June 2012, 26 pts were enrolled. Main characteristics were: M/F 19/7; median age: 71 yrs; single/multiple sites of metastases: 2/24, KRAS wt/mut: 18/8, BRAFwt/mut 25/1. 16 (62%) pts had received at least 3 previous lines of chemotherapy. Five pts were progression free at 2 mos, for a 2m-PFR of 19%. At a median follow up of 14.4 mos, median PFS and OS were 2.1 and 6.0 mos. No chemo-related G3/4 adverse events were reported. Conclusions: Metronomic cape and CTX demonstrated low clinical activity in heavily pretreated mCRC. Ongoing pharmacokinetic and dynamic analyses might provide additional data to interpret results and further insights into the antiangiogenic properties of this metronomic combination. Clinical effects of metronomic cape and CTX are under investigation in earlier settings and in association with other antiangiogenic agents.
Is there a role for chemotherapy in metastatic colorectal cancer patients with a poor performance status?
Authors: Wong Hui-li , Field Kathryn M , Tie Jeanne , Kosmider Suzanne , Shapiro Jeremy David , McKendrick Joseph , Parente Phillip , Lipton Lara Rachel , Yip Desmond , Parakh Sagun , Nott Louise M. , Gibbs Peter 
Published: March 2020

e14583 Background: The management of patients with poor performance status (PS) remains challenging in the absence of data on optimal treatment. Here we assessed the treatment and outcomes of patients with metastatic colorectal cancer (mCRC) with poor Eastern Cooperative Oncology Group (ECOG) PS (≥ 2) in routine clinical care. Methods: Analysis of patients prospectively entered onto the TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) database, a clinician-designed initiative to collect comprehensive data on consecutive patients with mCRC from sites across Australia. Data collection commenced in July 2009 and is ongoing at 14 participating public and private centers. Results: Of the 864 patients entered, 161 (18.6%) had an ECOG PS ≥ 2. In total, 95 (11.0%) were PS 2, 54 (6.3%) PS 3 and 12 (1.4%) PS 4. Chemotherapy was administered to 65 (68.4%) PS 2 and 17 (31.5%) PS 3 patients, with none of the PS 4 patients being treated. Overall, poor PS patients were significantly less likely to receive any chemotherapy compared to their good PS (PS 0-1) counterparts (51.6% versus 86.8%, p<0.0001) and, when chemotherapy was given, significantly less likely to receive combination chemotherapy (67.5% vs 81.1%, p=0.0057) or bevacizumab (31.3% vs 55.8%, p<0.0001). Overall survival (OS) was reduced with declining PS, with medians of 28.7, 8.9, 3.5 and 0.8 months for PS 0-1, 2, 3 and 4 patients respectively (p<0.0001). Poor PS patients treated with chemotherapy had a better OS outcome (9.0 vs 3.5 months for untreated patients, p<0.0001). At one and two years, 24 (28.9%) and 7 (8.4%) treated poor PS patients were alive. Conclusions: In routine practice many patients with a poor PS, particularly those that are PS 2, receive active treatment. Although overall survival for poor PS patients is poor, some patients appear to benefit from treatment. Further data analysis, particularly to define subsets that may benefit most from treatment, is planned as further sites around Australia contribute data to the project.
Is there any difference in overall response rate according to kras mutation in advanced colorectal cancer (aCRC)?
Authors: Rivadeneira Cabana José Antonio , Viudez Antonio , Guerrero David , Hernandez Irene , Gomez Dorronsoro Maria Luisa , Montes Marta , Verdun Juan , Tarifa Antonio , Suarez Javier , Fernandez de Lascoiti Angela , Ciga Lozano Miguel Angel , Vera Ruth 
Published: March 2020

e14589 Background: Tejpar et al (JCO2012; 30(29):3570-7) showed that patients with aCRC and Gly13D kras mutation experienced worse response rate with chemotherapy alone compared to those with other kras mutations. This retrospective study analyzes differences in clinical and radiological response between patients with the two main kras mutations: Gly12Val or Gly13D. Methods: In this retrospective-observational trial, patients with aCRC and Gly12Val and Gly13D kras mutation tumours participated. Clinical and radiological responses of patients with each of the two kras mutation, detected by Therascreen technique and treated with conventional first-line chemotherapy schemes, were recorded. SPSSv17 was employed. ORR (Overall Response Rate: CR+PR) and OCR (Overall Control Rate: CR+PR+SD) were calculated. Results: From November 2005 to October 2012, 51 patients with aCRC and Gly12Val or Gly13D kras mutations were included. Median age was 66 (41-80); 52.7 % men and 49.1% with synchronous disease. Kras mutation status was: 47.3% Gly13D and 52.7% Gly12Val. The chemotherapy schedules were based on Oxaliplatin, Irinotecan and others (61.5%, 25% and 13.5% respectively). While ORR was observed in 39.22 % (38.46 % Gly12Val and 40% Gly13D; p: 0.57), OCR was 76.5% (76.9% Gly12Val and 76% Gly13D; p: 0.60). In the Kaplan-Meier analysis, OS showed no difference between both kras mutation groups (Gly12Val: 29 months; Gly13D: 28 months; p: 0.28). Conclusions: According to our results, and in contrast to other studies outcomes, there is no difference regarding ORR, OCR or OS in patients with both different kras mutation: Gly12Val or Gly13D; however, the hypothetical role of Gly13D mutation as a biomarker of chemotherapy resistance, should be evaluated in prospective studies.
Relationship of the emergence of KRAS mutations and resistance to panitumumab in second-line treatment of colorectal cancer (CRC).
Authors: Blagoev Krastan B. , Burotto Pichun Mauricio Emmanuel , Wilkerson Julia , Blanco-Codesido Montserrat , Espinal Dominguez Edward , Garcia-Alfonso Pilar , Fojo Antonio Tito 
Published: March 2020

e14592 Background: Multiple analyses have concluded anti-EGFR antibodies are detrimental to a majority of patients (pts) whose CRCs harbor mutant KRAS. While panitumumab may benefit some pts with tumors harboring WT KRAS, in the majority the added benefit is small and transient. Recent studies have claimed emergence of KRAS mutations mediates acquired resistance to EGFR inhibitors. Methods: We analyzed published and unpublished data to assess this possibility, calculating growth and regression rate constants and estimating doubling times of CRC. Results: Amongst 24 pts with CRC whose tumors were initially KRAS WT, circulating mutant KRAS transcripts were detected in 9 treated in second line with panitumumab plus chemotherapy [Diaz et al, Nature 2012]. The growth rate of tumor in the 9 pts with circulating MT KRAS was 0.0019 days-1. This value is statistically indistinguishable [p = .2439] from the growth rate of 0.0021 days-1 calculated for tumors in 15 pts with no detectable circulating MT KRAS transcripts. Both values were also statistically indistinguishable [p = .3055 for MT KRAS; p = .7688 for WT KRAS] from the growth rate [0.002 days-1] of tumors in a cohort treated in second line with the same chemotherapy without an EGFR inhibitor. Similar results were observed when growth rates were calculated using CEA values [WT, 0.00087 days-1; MT, 0.0024 days-1; p = .1265] and similar regression rate constants were also calculated [WT, 0.0114 days-1; MT, 0.0117 days-1; p = .858]. Furthermore, in pts with detectable serum MT KRAS transcripts the growth rate remained constant even as MT KRAS transcripts appeared to increase. The growth rates allowed us to estimate tumor doubling times of 110 to 124 days in these pts receiving second line therapies, consistent with clinical data for disease progression in second line; and similar to the estimated doubling time of 116 days in the cohort that did not receive panitumumab. Conclusions: Resistance to panitumumab in tumors harboring WT KRAS cannot be explained by overgrowth of cells with MT KRAS. Other mechanisms must be sought to explain the limited efficacy of panitumumab. The data suggest such mechanism(s) are inherent and likely present in the majority of cells.
Worse prognosis of KRAS C.35 G > A mutant metastatic colorectal cancer (MCRC) patients treated with first-line triplet chemotherapy plus bevacizumab (FIr-B/FOx) and post-progression.
Authors: Bruera Gemma , Cannita Katia , Di Giacomo Daniela , Lamy Aude , Giordano Aldo Victor , Vicentini Roberto , Marchetti Paolo , Frébourg Thierry , Sabourin Jean-Christophe , Tosi Mario , Alesse Edoardo , Ficorella Corrado , Ricevuto Enrico 
Published: March 2020

e14596 Background: Prognosis of MCRC patients (pts) treated with bevacizumab (BEV) and chemotherapy (CT) is not significantly different according to KRAS genotype. Specificmutations confer different aggressiveness. Prognostic relevance of the prevalent c.35 G > A KRAS mutation was retrospectively evaluated in pts treated with first line FIr-B/FOx, and post-progression. Methods: KRAS codon 12/13 and BRAF mutations were screened by SNaPshot and/or sequencing. FIr-B/FOx: weekly 2 days/12h-timed-flat-infusion/5-fluorouracil 900 mg/m2, weekly alternating irinotecan 160 mg/m2/BEV 5 mg/kg, or oxaliplatin 80 mg/m2. Second-line treatment was selected according to fitness, KRAS genotype, previous efficacy and safety. Efficacy was evaluated and compared according to treatment or KRAS genotype, using log-rank. Results: At 21.5 months, 59 pts were evaluated. KRAS mutant pts: c.35 G > A, 15 (25.4%); c.35 G > T, 7 (11.8%); c.38 G > A, 3 (5%); other, 3 (5%). KRAS wild-type, 31 pts (52.7%). ORR, PFS, OS were, respectively: c.35 G > A, 71%, 9 months, 14 months; other mutants, 61%, 12 months, 39 months. OS was significantly worse in c.35 G > A pts compared to KRAS wild-type (p = 0.002), KRAS/BRAFwild-type (p = 0.03), other pts (p = 0.002), other mutants (p = 0.05), other codon 12 (p = 0.03) mutant pts; PFS was not significantly different. Post-progression, at 14 months follow-up, PFS and OS were significantly worse in c.35 G > A compared to wild-type and/or other mutant pts. ORR of second line treatments was 38%, metastasectomies 12.5%, PFS 10 months, OS 14 months. PFS and OS were significantly favourable in pts treated with triplet CT plus targeted agent compared to triplet, respectively: PFS 13 months versus 8 months; OS not reached versus 11 months. Conclusions: KRAS c.35 G > A mutation may significantly affect worse OS of MCRC pts. It does not significantly affect worse PFS of intensive first line FIr-B/FOx, while after progression significantly affect worse efficacy of second line treatments. Re-challenge of intensive regimens may affect significantly favourable PFS and OS.
Causes of urban-rural disparities in adjuvant chemotherapy (AC) for rectal cancer (RC).
Authors: Rasool Javaheri Khodadad , Moghaddamjou Ali , Speers Caroline , Cheung Winson Y. 
Published: March 2020

e14603 Background: While urban-rural differences in cancer care are well described, the etiology of these disparities is unclear. Our aims were to 1) characterize differences in AC use based on community size and 2) determine if such disparities are mediated through variations in driving distance (DD) and travel time (TT) to closest cancer center. Methods: Patients diagnosed with stage 2 and 3 RC from 1999 to 2009 and referred to any 1 of 5 regional cancer centers in British Columbia were reviewed. Communities were classified as rural, small urban, moderate urban and large urban based on census data. Using zip codes and a distance matrix application interface, DD and TT to the closest cancer center were determined and categorized into quartiles. Stepwise logistic regression models were constructed to explore AC use based on urban vs rural communities, adjusting for DD and TT. Results: A total of 3,017 patients were identified: median age was 67 years (IQR 58-75), 64% were men and 58% received AC. Patients were distributed across various communities: rural 36%; small urban 12%; moderate urban 13%; and large urban 39%. There were no differences in baseline patient and disease characteristics based on community size (all p>0.05). Compared to patients in large urban centers, those living in rural, small urban and moderate urban areas were less likely to be treated with AC (62 vs 49 vs 54 vs 58%, respectively, p<0.001). Likewise, DD and TT were shortest for large urban and longest for rural residents (both p<0.001). In multivariate analyses that controlled for confounders, urban-rural disparities in receipt of AC persisted, but these differences significantly diminished after adjusting for DD, TT, or both (Table). Conclusions: Urban-rural disparities in AC use is partly mediated by commute. Strategic distribution of cancer services that reduce DD and TT to cancer centers may improve access to AC for a number of RC patients who are living in smaller communities. [Table: see text]