bluuebunny/crossref_metadata_2025_split huggingface dataset:
Body weight and composition changes, primary tumor side, and resection as survival predictors in metastatic colorectal cancer.
Authors: Franko Jan , Graff Tara Michelle , McClairen Christian 
Published: January 2019

850 Background: Common symptoms of metastatic colorectal cancer (mCRC) are sarcopenia and weight loss. We investigated whether weight loss, sarcopenia and primary tumor resection can predict overall survival among patients (pts) with mCRC Methods: Consecutive pts newly diagnosed with mCRC in a community hospital between 2012-2014 we reviewed. We gathered initial and 6-month follow up data on weight, standardized muscle mass measure (estimated psoas muscle area/m2 height, sEPA) and subcutaneous fat (SQ). Results: There were 109 pts (age 66.9±14.5, range 37-93 years). Chemotherapy recipients were younger (n = 59, 61.2±13.3 years) and survived longer (22.3 versus 5.3 months, p < 0.001) as compared to best supportive care patients (n = 50, 73.6±13.0 years, p < 0.001). There were no baseline and 6-month differences between pts with resected versus in situ primary tumor in age (p = 0.074), baseline weight (p = 0.728) or percent weight loss (p = 0.404), albumin (p = 0.322), hemoglobin (p = 0.301), creatinine (p = 0.791), initial standardized EPA (p = 0.866), percent of sEPA loss (p = 0.952), and percent subcutaneous thickness loss (p = 0.477). Cohort was further dichotomized by median anthropometric changes at 6 months: -7.1% for weight loss, -6.2% sEPA, -3.3% SQ fat. Cox proportional hazard models demonstrated that anthropometric measures and receipt of systemic chemotherapy were the strongest predictors of survival with their predictive strength surpassing traditional predictors as age, tumor sidedness, primary tumor resection, initial BMI and serum albumin level. Conclusions: Weight loss and anthropometric changes are strongly associated with shorter survival. Prognostic characteristics of loss of weight, muscle and fat should be investigated further using more robust datasets. [Table: see text]
Clinical practice use of panitumumab combined with chemotherapy in patients with wild-type RAS metastatic colorectal cancer.
Authors: Hebart Holger Frithjof , Tomasek Jiri , Csõszi Tibor , Koukakis Reija , Kafatos George , Kuhn Anja , Björklöf Katja , Buchler Tomas 
Published: January 2019

852 Background: This study aimed to understand panitumumab (pmab) use in clinical practice for patients with wild-type RAS metastatic colorectal cancer (mCRC), in first-line (1L) with FOLFOX or second-line (2L) with FOLFIRI following fluoropyrimidine-based chemotherapy (excl. irinotecan). Methods: This is a combined analysis of two observational, non-interventional prospective cohort studies conducted in Germany/France (2012-2016) and Bulgaria/Czech Republic/Hungary (2013-2016). Results: Results are presented in the order of 1L FOLFOX (n = 332) followed by 2L FOLFIRI (n = 94). Patients received a median of 10 and 11.5 pmab infusions. The median duration of pmab exposure was 5.7 and 6.9 months (note that 53 and 10 patients continued pmab use after study end). The unadjusted overall response rate (complete or partial response) was 42% and 29%, based on 45% and 44% of patients with available response data post-baseline. In the 1L setting, resectability was achieved in 9%, not achieved in 42%, and unknown in 48%. Hospitalizations were reported for 100% and 99%, mostly cancer-related visits such as scheduled anticancer treatment (e.g. chemotherapy/pmab administrations), tumor assessment visits, or interventions; 93% in both groups reported outpatient, 66% and 60% inpatient visits. Conclusions: Overall, the study results show that treatment patterns and clinical efficacy of pmab in routine clinical practice were comparable to randomized controlled trials (RCTs). The ADR/SADR skin toxicity events are lower than expected based on findings from RCTs, however, similar findings have been shown in a previous observational study. More investigation is required to understand the reason for this.[Table: see text]
Current Status of mCRC in East Europe and Middle East.
Authors: Yazici Ozan , Ucar Gokhan , Vasileia Vamvakopoulou , Turhal Serdar Nazim , Yildiz Birol , Karamouzis Michalis , Yavuz Sinan , Karadurmus Nuri , Zengin Nurullah , Abali Huseyin , Geva Ravit 
Published: January 2019

853 Background: Results obtained in trials may not necessarily translate into prolonged survival of metastatic colorectal cancer (mCRC) patients (pts) in real life.This multinational registry study aimed to evaluate the real life data effecting survival of pts with mCRC. Methods: Multinational, retrospective registry study.Those mCRC pts with at least 3 year follow up data OR died before 3 year time period:diagnosis in between 2005 – 2012. Results: Totally 208 (57%) male,156 female (43%) mCRC pts were included.Median age was 62 years (min:23 max:85).Primary locations; right (n = 71, 19.5%), transvers (n = 13, 3.6%), left colon (n = 276,75%). Sites of metastasis: liver 69.7%, lung:27.4%, local relapse %12.6, peritoneum 12%, distant lymph node 10%, CNS: 1.6%. Metastasectomy (mtc) was done in 38.5%, mtc regions: liver (22.3%), lung (4.7%), other (%11.5 ). K-N RAS and BRAF wild pts were 37.4%, 16.5% and 14.3%. Aflibercept was available for %57 of pts. MSI rate was 1.6%. Most common first line chemotherapy (FLC); Oxaliplatin (O) based combination (C) 29.9%, irinotecan (İ) C with bevacizumab (bev) 16.5%, O with bev. 16.5%. Responses to FLC; CR: 8%, PR: 30.5% stable: 28.3%, progres: 24.7%. Median OS of FLC; combination with bev: 35 months (m) (95%CI, 29.1 – 40.8), anti-EGFR:38 m (95%CI, 30.1–45.8 ),only chemotherapy: 32 m (95%CI 26.3 - 37.6), p > 0.05. Second mtc was done 10.2%.Second LC was given to %66.7 of pts. İ combination with bev (24.5%) was most common SLC. Responses to SLC; CR:4.9%, PR: 15.1% , stable:13.2% progres:29.1%. Total %31.3 and 22% of pts had third and fourth LC, most common one was single agent 5-FU. Median PFS1: 10 m (95%CI 8.3 – 11.6 ), PFS2: 7 m (95%CI 6.2 –7.7 ), PFS3: 6 m (95% CI 4.6 – 7.3 ). Median OS of all pts were 35 m (95%CI 30.7 – 39.2 ). In pts with metastasectomy compared with others median OS was; 43 m (95%CI 34.4 – 51.5) vs 29 m (95% CI 25.8 vs 32.1), respectively , p: < 0.001. Median OS in right, transvers and left colon was; 25 m (95%CI, 16.6 – 33.3), 33 m (95%CI, 8.7 – 52.7), 37 m (95%CI 32.4 – 41.5), (p = 0.25). In K-N Ras wild group median PFS; anti-EGFR:13 m (95 % CI, 9.3 - 16.6) bev:13 m (95 %CI, 4.4 - 21.5), chemo:9 m (95 % CI, 6.3 - 11.6), (p: 0.3). Conclusions: The current study demonstrated median OS and prognosis of left-transvers-right colon was consistent with the phase trials.
A triplet combination with irinotecan, oxaliplatin, continuous infusion 5-fluorouracil and leucovorin (FOLFOXIRI) plus cetuximab as first-line treatment in RAS wild-type, metastatic colorectal cancer: A phase 1 dose finding study.
Authors: Kadowaki Shigenori , Masuishi Toshiki , Ura Takashi , Mitani Seiichiro , Narita Yukiya , Kato Kyoko , Honda Kazunori , Taniguchi Hiroya , Ando Masashi , Muro Kei 
Published: January 2019

856 Background: The FOLFOXIRI regimen (irinotecan, oxaliplatin, 5-fluorouracil and leucovorin) improves the response rate and overall survival compared to FOLFIRI in pts with metastatic colorectal cancer (mCRC), and addition of cetuximab to chemotherapy increases efficacy in pts with RAS wild-type mCRC. We conducted a phase 1 study of FOLFOXIRI plus cetuximab to determine the maximum-tolerated dose (MTD) and recommended dose (RD) and to assess its safety and efficacy in Japanese pts with RAS wild-type mCRC. Methods: Main eligibility criteria were: histologically confirmed colorectal adenocarcinoma; KRAS and NRAS wild-type status; measurable metastatic disease according to Response Evaluation Criteria in Solid Tumors version 1.1; age 20-74 years; Eastern Cooperative Oncology Group performance status 0 or 1. Pts with UDP-glucuronosyltransferase 1A1*6/*6, *28/*28 and *6/*28 genotypes were excluded. Pts received an escalating dose of intravenous irinotecan (100, 120, and 150 mg/m2 in the dose levels 0, 1, and 2, respectively) and a fixed dose of intravenous oxaliplatin (85 mg/m2), continuous infusion 5-fluorouracil (2400 mg/m2) plus l-leucovorin (200 mg/m2), and cetuximab (an initial dose of 400 mg/m2 followed by 250 mg/m2 per week). Results: A total of 9 Japanese pts were treated (3 and 9 in the dose levels 1 and 2, respectively). No patients experienced a dose-limiting toxicity (the MTD was not reached), and the dose level 2 (irinotecan 150 mg/m2) was established as the RD. With a median 8 cycles per patient, the most common grade 3 or 4 adverse events included neutropenia (44%), paronychia (22%), and acne-like rash (11%). No febrile neutropenia and treatment-related death were observed. Among 9 pts, 1 pt had complete response, 7 pts had partial response, and 1 pt had progressive disease, for an overall response rate of 89%. As of September 24, 2017, median progression free survival was 14.0 (95% CI 7.2-20.7) months. Conclusions: The combination of cetuximab and FOLFOXIRI has shown a favorable toxicity profile and promising antitumor activity in pts with RAS wild-type mCRC. Clinical trial information: UMIN000018217.
Factors associated with efficacy of TAS-102 in patients with refractory metastatic colorectal cancer (mCRC).
Authors: Grell Peter , Dvorak Josef , Vocka Michal , John Stanislav , Tuskova Helena , Buchler Tomas , Petruzelka Lubos B. , Vyzula Rostislav , Obermannova Radka 
Published: January 2019

858 Background: TAS-102 significantly improved progression free survival (PFS) and overall survival (OS) versus placebo in patients with treatment refractory mCRC. We analyzed potential predictive and prognostic factors in patients treated with TAS-102 in real-world practice. Methods: We retrospectively evaluated the clinical data of 129 patients who received TAS-102. Different factors associated with PFS and OS were analyzed. Results: Baseline characteristics were: median age 67 (range 37-83), male 63.6%, ECOG PS 0 in 40.3% and 1 in 59.7%. Primary tumor location: right 20.2%, left 79.2%, wt RAS 45%. Median number of TAS-102 treatment line 3 (range 2-8). Prior treatment: anti-EGFR 45%, anti-VEGF 83%, and regorafenib 20.9%. Median follow-up was 9.4 months. The median number of cycles of TAS-102 was 3 (range 1-14). Best achieved response was SD in 23%. Median PFS was 3.3 months and OS was 11.1 months. Any ≥ grade 3 AE was in 45%, the most common ≥ grade 3 AEs were neutropenia (40.2%), anemia (6.2%), thrombocytopenia (4.7%), febrile neutropenia (2.3%), diarrhea (1.6%), nausea (1.6%), and asthenia (1.6%). Dose reduction was needed in 29.5% and cycle delay in 53.5%. Factors significantly associated with longer PFS were: initiation of TAS-102 treatment more than 3 months from last fluoropyrimidine therapy (p = 0.022, HR 0.633), normal baseline CRP level (p = 0.004, HR 0.479), baseline WBC < 8 × 109/L (p = 0.025, HR 0.641), monocytes < 0.5 × 109/L (p = 0.016, HR 0.522), neutropenia ≥ grade 2 during treatment (p < 0.0001, HR 0.349), TAS-102 dose reduction during treatment (p < 0.0001, HR 0.397), and TAS-102 cycle delay (p < 0.0001, HR 0.402). Factors associated with longer OS were normal CRP (p = 0.001, HR 0.295), normal LDH (p = 0.006, HR 0.422), WBC < 8 × 109/L (p = 0.0001, HR 0.357), monocytes < 0.5 × 109/L (p = 0.016, HR 0.373), neutropenia ≥ G2 during treatment (p = 0.0002, HR 0.343), TAS-102 cycle delay (p = 0.002, HR 0.421), wt RAS (p = 0.05, HR 0.578). Conclusions: This analysis confirms that TAS-102 is effective in patients with refractory mCRC treated in a real-world setting. Factors associated with better outcomes were baseline CRP, WBC, monocytes, and neutropenia, dose reduction and cycle delays during the treatment.
Effect of IL-11 stimulated by co-culture with CAF on metastasis of gastric cancer cells mediated by upregulation of MUC1.
Authors: Wang Xiaoxun , Che Xiaofang , Liu Yunpeng , Qu Xiujuan 
Published: January 2019

86 Background: Cancer-associated fibroblasts (CAFs), as the activated fibroblasts in tumor stroma, are important modifiers of tumor progression. However, the molecular mechanisms underlying the tumor-promoting properties of CAFs in gastric cancer remain unclear. Methods: We show that when CAFs co-cultured with gastric cancer cells, two kinds of cells produce significant amounts of interleukin-11 (IL-11). CAFs enhances the migration and invasion of gastric cancer cells through the secretion of IL-11 that activates JAK/STAT3 and MAPK/ERK pathways to upregulate MUC1 in gastric cancer cells, while deprivation of IL-11 using a neutralizing antibody or inhibition of JAK/STAT3 and MAPK/ERK pathway with specific inhibitor Stattic and PD-98059 markedly attenuates these phenotypes in gastric cancer cells induced by CAFs. Results: In this study, we find that CAFs in the tumor microenvironment promote the progression of gastric cancer through IL-11-JAK/STAT3 and MAPK/ERK signalings to upregulate MUC1. Conclusions: Taken together, these results suggest that CAFs promote the progression of gastric cancer and IL-11 targeted therapy could be a complementary approach against gastric cancer by exerting their action on stromal fibroblasts.
Effective use of electronic medical record (EMR) data in analysis of association between KRAS mutations and depression in colorectal cancer patients.
Authors: Li Jenny Jing , Harper Jessica , Zhu Hong , Bhulani Nizar , Guenther Chad Michael , Madrigales Alejandra , Gates Samantha , Kazmi Syed Mohammad Ali , Verma Udit , Toups Marisa , Beg Muhammad Shaalan 
Published: January 2019

861 Background: Previous studies have demonstrated that KRAS mutations were associated with higher rates of depression in patients with metastatic colorectal cancer (CRC). The objective of this study was to evaluate the feasibility of extracting EMR data to examine the association between KRAS mutations and positive screening test for depression in CRC patients. Methods: Retrospective review of stage I to IV CRC patients seen between 2011 and 2015 at an academic, NCI-Designated Comprehensive Cancer Center was performed. At each clinic visit, depression was assessed using the Patient Health Questionnaire-2 (PHQ-2), which is part of the institution’s universal Distress Screening tool. PHQ-2 score of 2 and above was considered positive screening test for depression. PHQ-2 and KRAS mutation data were extracted from the EMR via the Clinical Data Exchange Network bioinformatics tool and confirmed by retrospective chart review. Chi-square test was used to assess the association between KRAS mutation and depression. Multiple imputation was used to impute the missing values. Results: Of the 484 CRC patients, KRAS status was known in 45 cases: 22 (49%) were KRAS mutated and 23 (51%) were KRAS wild type. PHQ-2 score was 0 in 42 cases (93.3%), 1 in 2 cases (4.4%), and ≥2 in 1 case (2.3%). The rate of positive PHQ-2 for KRAS mutated vs wild type was 4% vs 0% (p = 0.36). The result based on 50 imputed datasets suggests a trend towards an association between KRAS mutation and depression (p = 0.09). Conclusions: This study did not demonstrate an association between KRAS mutation and depression in patients with colorectal cancer, probably due to a high proportion of missing data. Bioinformatics studies that extract and analyze EMR data are a feasible and effective platform to assess the association of genomic data with clinical outcomes. Additional validated algorithms and data are needed to further optimize such studies.
Metastases resection after FOLFIRI-aflibercept (FA) in oxaliplatin-refractory colorectal cancer patients (ORF-CRC).
Authors: Muñoz Martín Andres J. , Garcia Adrian Silvia , Pericay Carles , Ruíz Ana , Ibeas Patricia , Grandez Rosana , Diaz Pena Elena , Lopez Ana Maria , Ignacio Juez MARTEL , Gonzalez Cebrian Irene , Encinas García Sara , Alcaide Julia , Fernandez Montes Ana Fernandez , Soriano Carmen , Macarulla Teresa Mercade , García-Paredes Beatriz , Pulido Gema , Mazo Jose M. , Rodriguez Salas Nuria , Garcia Alfonso Pilar 
Published: January 2019

862 Background: Recent data suggest resection of colorectal metastases after second-line chemotherapy offers similar overall survival (OS) benefit compared to what described in first-line. The improvement in response rate with FA in second-line may increase the number of patients eventually undergo metastases resection. Methods: We performed a retrospective analysis of 32 patients from 26 Spanish hospitals who underwent surgical resection after FA in ORF-CRC in real-life setting. Our aim was to analyze the impact of metastases resection in different organs (liver, lung, etc.) in terms of OS and progression-free survival (PFS) and post-surgical mortality and morbidity. Results: Clinical characteristics: Median age: 65 years (43-83). Sex: 78.1% male, 21.9% female. ECOG 0/1 53.1/46.9%. Ras: wild-type/mutated 25/75%. Type of tumor: colon 75.0%, rectal 25.0%. Location: right 28.1%, transverse 9.4%, and left-side 62.5%. Previous treatment: oxaliplatin combinations (100%), bevacizumab 37.5%, cetuximab 21.97%. Ras wild-type patients received previous anti-EGFR therapy. FA in second-line 93.7% and beyond second-line 6.3%. Median FA cycles before surgery: 6.5 (range 3-44). Type of surgery: liver metastases 46.9%, lung metastases 25.0%, cytoreductive surgery for peritoneal carcinomatosis 15.6%, supraadrenalectomy 3.1%, simultaneous liver and peritoneal carcinomatosis 9.4%. Better tumor response with FA (RECIST1.1): partial response 56.3%, complete response 3.1%, stable disease 40.6%. Median follow-up: 20.9 months [m] (range 3.8-57.3 m). Median PFS from surgery: 8.0 m (confidence interval [CI] 95% 2.5-13.5 m). Median OS from surgery: 37.3 m (CI 95% 23.3-51.4 m). No significant difference between right and left-side tumors in OS or PFS were observed. 90-day postoperative mortality/morbidity: 18.8/0% Reoperation rate: 9.4%. Resection rates: R0 75.0%, R1 15.6%, R2 9.4%. Aflibercept after surgery: 22% patients. Conclusions: Metastases resection following FA in ORF-CRC offers encouraging OS with favorable surgical mortality and morbidity. Salvage surgery should be considered in highly selected patients in second-line setting with oligometastatic disease.
Adjuvant therapy for stage II and III colon cancer in elderly patients: NCDB analysis.
Authors: Master Samip R. , Shi Lawrence , Shah Chintan , Shi Runhua 
Published: January 2019

863 Background: Data on safety and efficacy of adjuvant chemotherapy for stage II and III colon cancer in elderly patients is area of controversy as these patients are underrepresented in clinical trials. We did a retrospective analysis of Medicare patients aged 70 or older with stage II and stage III colon cancer to investigate the adjuvant chemotherapy effect on colon cancer patients’ survival. Methods: Data was analyzed from 110, 993 men and women (≥ 70 years of age) registered in the National Cancer Database (NCDB) who were diagnosed with AJCC Stage II and Stage III colon cancer between 2004 and 2012 and had follow-ups to end of 2013. The primary predictor variable was adjuvant chemotherapy received, and overall survival was the outcome variable. Only patients with Medicare insurance were investigate for ease of analysis. Additional variables addressed and adjusted included gender, age, race, Charlson Comorbidity Index, the level of education, income, grade of tumor, distance traveled, facility type and diagnosing/treating facility. Results: The mean age was 79.5 years and SD was 5.9 years. In multivariate analysis, after adjusting for secondary predictor variables, receipt of adjuvant chemotherapy was a statistically significant predictor of overall survival of the stage II and stage III colon cancer. Relative to patients who did not receive adjuvant chemotherapy, the patients who got single agent adjuvant chemotherapy had 47.7% and those who were treated with multi agent chemotherapy had 49.8% decreased risk of mortality. There was no significant survival difference between single agent and multi agent adjuvant chemotherapy. Among the factors analyzed, age, gender, race, comorbidity index, diagnosing /treating facility and grade of tumor were found to be significant predictors of survival. Conclusions: Among the patients aged 70 years or older with stage II and stage III colon cancer, adjuvant chemotherapy lead to improved survival outcomes. However, survival difference between single agent vs multi agent adjuvant chemotherapy was not statistically significant.
Local excision for stage I anal canal squamous cell carcinoma (ACSCC): A case series from Mayo Clinic.
Authors: Jin Zhaohui , Chakrabarti Sakti , Hallemeier Christopher Leigh , Mahipal Amit 
Published: January 2019

864 Background: Definitive chemoradiotherapy (CRT) is the standard of care for localized or locally advanced ACSCC, while surgery is typically reserved for salvage therapy. Outcome of treatment with local excision alone is unknown and is currently not recommended by NCCN. We retrospectively analyzed outcome of the patients with small (T1 lesion) incidentally found ACSCC who were treated with local excision alone. Methods: On retrospective analysis, a cohort of 12 patients with pathologically confirmed stage I ACSCC treated at Mayo Clinic between 1994 and 2014 was identified who were managed with local excision alone. Baseline as well as followup data were obtained by electronic chart review. Results: Median age of the patients at diagnosis was 68 years (range: 36-81 years) and majority were females (76.9%). Median follow-up duration was 7.5 years. Of the 12 patients, 2 patients did not receive standard CRT due to co-morbid conditions and other 10 patients chose surveillance over CRT. There was only one patient with disease recurrence at 3 years which was salvaged by abdominoperineal resection (APR). This subject remains alive and disease free at the time of data collection (4 years out from APR). There were 4 deaths, all unrelated to ACSCC. Of 12 patients, 10 patients (83%) remained disease free at 5 years and beyond, 1 patient had recurrence and 1 patient was lost to follow up at 5 months from diagnosis. Conclusions: Local excision as a single modality of treatment may be safe and effective for highly selected small stage I ACSCC. Further clinical study is warranted to accurately define the patient population who can be treated with local excision alone, potentially sparing them long term toxicities.