bluuebunny/crossref_metadata_2025 huggingface dataset:
Gemcitabine plus nab-paclitaxel use in metastatic pancreatic cancer: A study of 40 patients.
Authors: Barrera Ivan , Filimon Sabin Dragos , Meng Jassy , Kavan Tomas , Rho Young soo , Batist Gerald , Kavan Petr
Published: March 2017

498

Background: Metastatic pancreatic adenocarcinoma (mPDAC) carries a dismal prognosis, with often a poor response to treatment (Tx). Although gemcitabine with nab-paclitaxel (GnP) is now a standard 1st-line (1L) Tx in mPDAC, provincial policies limit its use. To understand the implications of the restriction, this real-life study was conducted. Methods: A historical prospective data was compiled using the local electronic medical record (Endovault Oncology v3.0, NY) at the Jewish General Hospital-McGill. All patients (pts) diagnosed with mPDAC that received GnP from 2013-2016 were identified. Demographics and Tx data was obtained. Primary objective was to evaluate tolerability in all lines of Tx [grade >2 CTCAE v4.03, mean Tx delay (mTxd)]. Secondary objectives were Tx attrition and outcomes [RECIST 1.1, complete response (CR), stable disease (SD) and progression disease (PD)]. Results: Of the 40 pts (female 60%, median age 64.3), 25 (62.5%) had primary at the head of the pancreas and 30 (75%) liver metastasis. 1L Tx: GnP 24 (60%), FOLFIRINOX 10 (FFX, 25%), Gemcitabine 5 (Gc, 12.5%) and FOLFOX 1 (2.5%). 70% of both FFX and Gc pts had grade 2 peripheral neuropathy (PN), neutropenia (NEUT) and fatigue. Half GnP pts had grade 2 NEUT and fatigue. mTxd in GnP, FFX and Gc were 7, 14 and 7 days. All FFX and Gc pts had PD. GnP cohort had 1 CR and 7 SD. 2L Tx was in 22 (55%): GnP 13 (59.5%), FFX 3 (13.5%), Capecitabine 2 (9%), FOLFOX 2 (9%) and Gc (9%). FFX pts 66.6% had grade 3 fatigue. GnP pts had grade 2 NEUT, PN and fatigue in 53.8%, 15.3% and 46.2%. mTxd were GnP 14 days and FFX 14 days. Except 1 SD, all FFX pts had PD. GnP pts had 1 CR, 6 SD, and 6 PD. All pts on Capecitabine, FOLFOX and Gc had PD. 3L Tx was in 6 (15%): 3 GnP (50%) and 3 on clinical trials (50%). All pts had PD and < 3 cycles. In 1L FFX pts, 7/10 and 3/6 went on to receive GnP in 2L and 3L. All 1L Gc pts had 2L GnP. Only 3 pts and 1 pt from 1L GnP pts went on to receive 2L and 3L Tx. Conclusions: Due to access limitations to GnP, its use was likely reserved for poor performance status pts. Instead, 1L FFX was used when possible. 1L FFX pts received more Tx lines due to initial pt selection. Further studies are needed in broader populations to evaluate optimal 1L Tx selection accounting for expected attrition and overall survival.
Analysis of PDL1 expression and T cells infiltration in 1014 gastric cancer patients.
Authors: Xing Xiaofang , Li Ziyu , Wang Jiping , Ji Jiafu
Published: March 2017

50

Background: Although immune checkpoint inhibitors have demonstrated promising results in melanoma and lung cancer, their effects on gastrointestinal cancer are still under investigation. Understand the prognostic effect of PDL1 expression, infiltration by CD8+ and CD3+ T cells in gastric cancer (GC) might help the identification of candidate patient who might benefit from immunotherapy. Methods: Immunohistochemistry were performed on a tissue microarray including 1,014 GC specimens with PD-L1 antibodies. Immune cell markers CD3 and CD8 were also stained and the quantitative differences were calculated using automated image analysis. Results: 37.8% of the cases showed a membranous PD-L1 expression in tumor cells and 74.9% in tumor infiltrating immune cells. GC patients with high level PDL1 expression in tumor cells or in immune cells were both associated with better survival compared with those with negative expression (5-year OS, 61% vs. 48%, P = 0.000, and 55% vs. 45%, P < 0.0001, respectively). As continuous variables, higher CD3+ and CD8+ cell density were associated with patients’ overall survival and the associations remained as the significant prognostic factors that predict favorable outcomes even after adjusting other unknown confounding factors.(HR: 0.974, 95%CI: 0.963-0.985, P = 0.000; and HR: 0.973, 95%CI: 0.960-0.986, P = 0.000 for CD3 and CD8 respectively). We also observed the close relationship between CD3+, CD8+ cell density and PDL1 expression both in tumor cells and in infiltrating immune cells. Conclusions: This study indicates that PDL1 expression, and TILs in particular, are important prognostic biomarkers. Patients with higher CD8 and CD3 T cell densities also have higher PD-L1 expression, indicating an adaptive immune resistance mechanism may be occurring. The counterintuitive observation that higher PD-L1 expression associating with better patients’ outcome highlights the need to assess both PDL1 expression in all tumor compartments and the characterization of the GC immune microenvironment.
Association of specific gene expression profiles with a pathologic complete response to neoadjuvant therapy in esophageal adenocarcinoma.
Authors: McLaren Patrick James , Barnes Anthony P , Terrell Willy Z , Vaccaro Gina M. , Wiedrick Jack , Hunter John G. , Dolan James P.
Published: March 2017

51

Background: Predicting prognosis in esophageal cancer remains an unrealized goal despite studies linking constellations of genes to therapeutic response. In this study, we analyzed specific predictor genes expressed in tumor specimens from our institutional repository. Our aim was to determine if specific gene expression profiles are associated with pathologic complete response (pCR) after neoadjuvant chemo-radiotherapy (CRT). Methods: We investigated eleven genes identified from prior studies (CCL28, SPARC, S100A2, SPRR3, SIRT2, NOV, PERP, PAPSS2, DCK, DKK3, ALDH1) that have significant association with esophageal cancer progression. Patients with esophageal adenocarcinoma treated with neoadjuvant CRT followed by esophagectomy at our institution between January 2011 and July 2015 were included. Quantitative real-time polymerase chain reaction was conducted on pre-treatment biopsy specimens to determine gene expression. Patients were classified into two groups: 1) pCR and, 2) no or poor response (NR) after CRT based on final pathology report. An omnibus test using Mahalanobis distance was applied to evaluate overall genetic expression differences between groups. Log-rank tests compared the differential expression of individual genes. Results: 29 patients (11 pCR and 18 NR) were analyzed. Overall, gene expression profiles were significantly different between pCR and NR patients (p < 0.01). In particular, CCL28 was over-expressed in pCR (Log-HR: 1.53, 95%CI: 0.46-2.59, p = 0.005), and DKK3-was under-expressed in pCR patients (Log-HR: -1.03 95%CI: -1.97, -0.10, p = 0.031). Conclusions: Esophageal adenocarcinoma patients with a pCR after neoadjuvant therapy have genetic profiles that are significantly different from typical NR profiles. In our population, the genes CCL28 and DKK3 are potential predictors of treatment response.
Comparing mortality of colorectal cancer and gastrointestinal bleeding among patients with long-term use of low dose aspirin: A population-based study of 689,209 patients.
Authors: Sung Joseph , Tsoi Kelvin Kf
Published: March 2017

527

Background: Aspirin, commonly used for prevention of cardiovascular and cerebrovascular diseases, is well-known to protect against colorectal cancer (CRC) development but increase risk of gastrointestinal bleeding (GIB). Few large-scale studies have compared the benefit and risk of long-term aspirin usage. This cohort study aims to evaluate the use of low-dose aspirin to prevent CRC and the risk of GIB associated with the aspirin use. Methods: A population-based clinical dataset was used to compare incidence and mortality of CRC and GIB patients receiving low-dose aspirin with sex-and-age matched controls (in 1:2 ratio). Patients with aspirin≤6 months were excluded. Clinical data of 206,243 aspirin users (mean dose 80 mg/day, mean duration 7.7 years) and 482,966 non-users were included. All patients must have at least 10-year follow up on clinical outcome. Results: Among aspirin users 5,776 (2.80%) were diagnosed with CRC; 2,097 (1.02%) died of the malignancy. 16,483 (3.41%) non-users were diagnosed with CRC; 7,963 (1.65%) died of CRC. Using the cox-proportional hazard regression, aspirin usage showed a modest but significant reduction in CRC mortality (HR = 0.65; 95% CI = 0.62 to 0.69). On the other hand, 11,187 (5.42%) aspirin users developed GIB, and 841 (0.41%) died. 15,186 (3.14%) non-users developed GIB, and 1,682 patients (0.35%) died. Aspirin users showed modest but significant increased risk of GIB-related mortality (HR = 1.24; 95% CI = 1.14 to 1.35). Conclusions: The long-term use of low dose aspirin shows preventive effect on CRC, but also increases the associated GIB risk. Considerations of prophylactic use of aspirin should balance the benefit and the risk of this treatment to the target population. [Table: see text]
Impact of adjuvant chemotherapy on recurrence risk in stage II colon cancer.
Authors: Adesoye Taiwo , Hu Chung-Yuan , Cuddy Amanda , Francescatti Amanda B. , Schumacher Jessica R. , You Y. Nancy , Van Loon Katherine , Schrag Deborah , McKellar Daniel P. , Winchester David Porter , Chang George J.
Published: March 2017

533

Background: Although clinical guidelines recommend consideration of adjuvant chemotherapy in high-risk stage II colon cancer, the impact on recurrence risk and cancer related survival is unclear. Furthermore, among Medicare patients, adjuvant chemotherapy was not associated with improved survival. We examine the effect of adjuvant chemotherapy on recurrence risk and overall survival in a diverse cohort. Methods: 6,095 patients who underwent surgery for stage II-III colon cancer (2006-2007) were randomly selected from facilities reporting to the National Cancer Data Base for additional abstraction of tumor information, 5 year recurrence and survival. Death or second cancer within 6 months were excluded. Patients were classified as high or low risk using standard pathologic factors. Multivariate Cox regression with propensity score weighting was performed to compare recurrence risk and overall survival. Results: Of 3,423 patients with stage II colon cancer, 26.9% (n = 883) received chemotherapy compared to 76.2% (n = 1,839) of stage III patients. Among stage II patients, 47.8% (n = 1,636) had at least one high risk feature and 30.8% (n = 481) of these received chemotherapy. Five year recurrence rate in stage II patients was 13% (n = 392), greater in high risk compared to non-high risk patients (13.3% vs 9.3% p < 0.0001) and 24.4% (n = 874) in stage III patients. Chemotherapy did not improve recurrence risk in stage II patients regardless of risk status (High risk: hazard ratio [HR] 1.37; 95% CI 0.96 - 1.97; Non-high risk: HR 1.39; 95% CI 0.91 - 2.11). Chemotherapy was associated with a significant improvement in recurrence risk in stage III patients (HR 0.79; 95% CI 0.63 - 0.96). However, chemotherapy was associated with improved overall survival in both high (HR 0.69; 95% CI 0.51 - 0.92) and non-high risk stage II patients (HR 0.76; 95% CI 0.55 - 1.04), and also in stage III patients (HR 0.47; 95% CI 0.41 - 0.54). Conclusions: Adjuvant chemotherapy was not associated with a lower recurrence rate among stage II colon cancer patients. The observed survival benefit associated with chemotherapy is likely attributable to non-oncologic factors such as patient selection. Decision-making regarding chemotherapy use in this cohort should be carefully approached.
The association between insurance status and survival in patients with stage III colon cancer.
Authors: Ahmed Aabra , Walters Ryan W , Tahseen Ahmed Ibrahim , Silberstein Peter T.
Published: March 2017

535

Background: Colon cancer is the third most frequent cancer diagnosis, and primary payer status has been shown to be associated with treatment modalities and survival in cancer patients. The goal of our study was to determine between-insurance differences in survival in patients with pathologic stage III colon cancer using data from the National Cancer Data Base (NCDB). Methods: We identified 130,998 patients with pathologic stage III colon cancer in the NCDB diagnosed between 2004 and 2012. Kaplan-Meier curves and multivariable Cox regression models were estimated to determine the association between insurance status and survival. Results: Private insurance patients were 41% less likely than Medicaid patients to die, 28% less likely to die than uninsured patients, and 14% less likely to die than those with Medicare (p<0.01). Medicare patients were 18% were less likely to die compared to uninsured patients (p<0.01) and 19% less likely to die compared to Medicaid patients (p<0.01). Medicaid and noninsured patients had comparable likelihoods of dying (p=0.76). Those with no comorbidities were 36% less likely to die than those with 2+ comorbidities (p<0.01). Each additional year in age added a 3% likelihood of dying (p<0.01). Patients with chemotherapy were 57% less likely to die compared to patients not receiving chemotherapy (p<0.01). Private insurance had the greatest percentage of patients receiving chemotherapy at 82%. Conclusions: Of all variables examined, chemotherapy provided the greatest increased chance of survival. Comorbidities were also a significant contributor to survival. Private and Medicare patients were likely to survive longer than uninsured and Medicaid patients. Furthermore, having Medicaid did not provide an advantage in survival over having no insurance. [Table: see text]
Molecular characterization of squamous cell carcinoma of the anal canal (SCCA).
Authors: Weinberg Benjamin Adam , Lenz Heinz-Josef , Arguello David , El-Deiry Wafik S. , Xiu Joanne , Gatalica Zoran , Liu Zhuqing , Chen Sting , El Ghazaly Hesham , Hwang Jimmy J. , Philip Philip Agop , Shields Anthony Frank , Marshall John , Salem Mohamed E.
Published: March 2017

538

Background: Nivolumab has shown promising results in SCCA patients. The majority of SCCA cases have been linked to prior human papillomavirus (HPV) infection. However, HPV negative tumors are frequently TP53 mutated and often resistant to therapy. Molecular characteristics of SCCA are largely undefined. Here we explored the underlying biology of SCCA and the differences between TP53-wild type ( TP53-WT) and TP53-mutated ( TP53-MT) tumors. Methods: SCCA specimens underwent multiplatform testing with protein expression (IHC), gene amplification (ISH), and sequencing (NGS). Tumor mutational burden (TMB) was calculated using only somatic nonsynonymous missense mutations. Chi-square tests were used for comparative analyses. Results: In total, 253 tumors were studied. The most frequently mutated genes included PIK3CA (24%), BRCA2 (14%), FBXW7 (12.4%), TP53 (9.7%), and PTEN (8.9%). In a subset of 23 tumors subjected to Illumina NextSeq (592 gene) testing, the most common mutations were NOTCH2 (30%), NOTCH1 (27.3%), POLE (21.7%) , TSC2 (17.4%), PTEN (14.3%), BRAF (13.6%), BRCA2 (13.0%), PIK3CA (13.0%), and FBXW7 (9.5%). Tumors frequently expressed MRP1 (97.6%), EGFR (92.7%), TOP2A (88.5%), TOPO1 (69.5%), MGMT (67.8%), and RRM1 (59.9%). Expression of PD-1 was seen in 55.8% (24/43) of tumors, and PD-L1 in 15.4% (9/34). HER2 was amplified in 2% (3/147) of samples, which has not been previously described in SCCA. When compared with TP53-WT (n = 93) tumors, T P53-MT (n = 10) had higher rates of BRAF (22% vs. 1%, p < 0.001) and RB1 mutations (44% vs. 0%, p < 0.001), whereas TP53-WT had higher expression of TOPO1 (76% vs. 40%, p = 0.01) and TUBB3 (19% vs. 50%, p = 0.02). There were no differences between the two groups in the frequency of PD-1 or PD-L1 expression. Mean TMB was 8.6 mutations/megabase and, using a TMB cut-off > 17 mutations/megabase to define high vs. low TMB, 6.7% of tumors were TMB-High. High TMB did not correlate with PD-1 (p = 0.50) or PD-L1 status (p = 0.52). Conclusions: Molecular profiling differences between TP53-MT and TP53-WT SCCA indicate different carcinogenic pathways and biology, which may influence response to therapy. Low frequency mutations in several druggable genes may provide therapeutic opportunities for patients with SCCA.
Direct access screening colonoscopy as a safe and effective approach to increasing colorectal cancer screening.
Authors: Estrada Joaquin J , Bedon Ana M , Kaminski Jan P , Rodriguez Gabriel , Ali Mahmoud , Albert Andrew
Published: March 2017

540

Background: This year 135,000 patients will be diagnosed with colorectal cancer (CRC) and it is the second leading cause of cancer deaths in the US. CRC is largely preventable when screening is conducted. Nearly 60% of patients over 50 report never receiving any form of CRC screening. Colonoscopy remains the gold standard for CRC screening. Unfortunately, several barriers exist to obtaining this life-saving screening option (i.e. access to gastroenterologists, patient anxiety and lack of knowledge about the procedure). Our Direct Access Screening Colonoscopy program (DASC) has provided a successful solution to address many of these deterrents. Methods: In July 2015, the DASC program was launched at Advocate Illinois Masonic Medical Center. A nurse navigator telephonically completes health questionnaires and if patients were determined to be without significant comorbidities, they would be enrolled in the program. Prior to the procedure, the nurse would address all questions, instructions and bowel preparations. Patients that were not eligible for the program were navigated to a gastroenterologist for a formal evaluation. A retrospective review of all patients that underwent screening colonoscopy from July 2015 to July 2016 was conducted. Data collected included patient demographics, quality of preparation, Adenoma Detection Rate (ADR), patient satisfaction, and complications. Results: A total of 644 patients were referred for DASC. 373 patients (58%) were eligible for inclusion within the program. At the time of submission, 289 completed their colonoscopy. 201 patients (70%) had a normal colonoscopy. 88 patients were found to have at least one adenoma (ADR- 30%). No patients experienced any complications following DASC. Patient satisfaction scores were significantly higher for those who underwent DASC. The overall screening rate nearly doubled after implementation of the DASC program (30% vs 59%). Conclusions: Direct Access Screening Colonoscopy is a novel method to that increased the overall screening rate for CRC by almost 100%. It is a safe and effective alternative to the conventional process of obtaining a colonoscopy and can positively impact patient satisfaction and outcomes.
The correlation between mismatch repair status and clinicopathological characteristics in Chinese colorectal cancer patients.
Authors: Xiao Zhi-tao , Zhang Rong-xin , Zhao Yang , Peng Jian-Hong , Ding Pei-Rong , Wu Xiao Jun , LU Zhen-hai , LI Li-ren , Wan Desen , Pan Zhi-zhong , Zhang Hui-Zhong , Lu Shi-xun , Chen Gong
Published: March 2017

544

Background: Our study aimed to explore the relationship between mismatch repair (MMR) status and clinicopathological characteristics in Chinese patients with colorectal cancer (CRC). Methods: A total of 2684 patients with histologically confirmed adenocarcinoma of CRC were consecutively recruited between May 2011 and May 2015 at Sun Yat-sen University cancer center. The exclusion criteria included multiple primary tumors, synchronous and metachronous CRC, and familial adenomatous polyposis. The CRC was defined as left colon with the tumor located below the splenic flexure or rectum, otherwise grouped as right colon. Correlations of MMR status and patient’s demographics, tumor characteristics and TNM staging (exclude 315 CRC patients receiving neoadjuvant therapy) were investigated. Results: We found that deficient MMR (dMMR) status was more likely detected in younger CRC patients compared to the the elderly (12.7% vs 7.5%, P < 0.001). The dMMR rate in right colon cancer was significantly higher than that in left colon cancer and rectal cancer (22.7% vs 7.2% vs 5.2%, P < 0.001).With respect to tumor differentiation, we found that the mucinous adenocarcinoma had the highest rate of dMMR(24.4%), followed by poorly differentiated adenocarcinoma(18.5%), signet-ring cell carcinoma(17.6%), well differentiated adenocarcinoma(9.5%), moderately differentiated adenocarcinoma(8.9%), and neuroendocrine carcinoma (0%) ( P < 0.001). In addition, the proportions in stage I, stage II, stage III and stage IV CRC were 9.7%, 16.5% , 8.5% and 3.9%, respectively ( P < 0.001). There was no significant difference in gender (P = 0.114). Conclusions: At the first time, our study demonstrated that dMMR status was most likely detected at younger age (less than 59 years) and stage II right colon mucinous adenocarcinoma in large volume Chinese patients, which was similar to the results in western countries.
Tracking emerging KRAS, BRAF and EGFR mutations through ccfDNA in colorectal cancers treated with EGFR blockade.
Authors: Yamada Takeshi , Takahashi Goro , Iwai Takuma , Takeda Kouki , Koizumi Michihiro , Shinji Seiichi , Matsuda Akihisa , Yokoyama Yasuyuki , Furuki Hiroyasu , Hara Keisuke , Matsumoto Satoshi , Ohta Keiichiro , Eiji Uchida
Published: March 2017

547

Background: Epidermal growth factor receptor (EGFR) blockade can achieve considerable tumor shrinkage in patients with metastatic colorectal cancer (CRC). However, most patients who benefit from EGFR blockade acquire resistance within a year through emerging KRAS, BRAF or EGFR ( S492R) mutations. We have shown that patients with KRAS or BRAF mutations in circulating cell-free DNA (ccfDNA) do not respond favorably to EGFR blockade. In this study, we aimed to detect acquired resistance to EGFR blockade early by using ccfDNA to track emerging KRAS, BRAF and S492R mutations during chemotherapy. Methods: We enrolled 24 patients with metastatic CRC and no KRAS mutations in their primary tumors who were to be treated with systemic chemotherapy that included EGFR blockade. We purified ccfDNA from 1 mL of serum from each patient before they started chemotherapy. We also extracted ccfDNA from these patients every 2–3 months until disease progression. We detected nine KRAS, BRAF (V600E) and S492R mutations using digital polymerase chain reaction. Results: We detected KRAS mutations in ccfDNA of three patients before chemotherapy (12.5%; 3/24). The response rate was 83% (20/24); the four non-responders comprised the three with KRAS mutations and the other with BRAF mutations in their ccfDNA before chemotherapy. All patients with no KRAS or BRAF mutations in their ccfDNA before chemotherapy responded to the chemotherapy (20/20). Of these 20 initially responsive patients, 12 (60%) acquired resistance. We detected emerging KRAS mutations in the ccfDNA of eight of these 12 patients (67%) prior to relapse, six of them having multiple mutations. Five of these patients had mutations in codon 61 and one had solo codon 61 mutations. We also detected BRAF mutations in five patients; none had solo BRAF mutations. Four patients had S492R mutations; none had solo S492R mutations. Conclusions: If KRAS or BRAF mutation do not detected in primary tumor, EGFR blockade has no beneficial effect in patients with KRAS or BRAF mutations in their ccfDNA prior to commencing chemotherapy. Emerging KRAS, BRAF or S492R mutations that were undetectable before starting chemotherapy are associated with acquired resistance to EGFR blockade.
Demographic factors and rate of lymph node evaluation in colon cancer stage II using National Cancer Database (NCDB).
Authors: Tahseen Ahmed Ibrahim , Ahmed Aabra , Silberstein Peter T.
Published: March 2017

548

Background: Retrieving at least 12 lymph nodes (LN) is a quality indicator in colon cancer. Previous studies have shown about 38% of patients with stage II are estimated to have ≥12 LN checked. Methods: Community Programs (CCP) receive 100-500 newly diagnosed cancer cases per year. Hospitals receiving 500+ patients are either Academic Comprehensive Programs (ACP) or Comprehensive Community Programs (CCCP). Using NCDB (2003-2013), which includes >70% of newly diagnosed cancer patients, we utilized chi-square analysis, and compared frequencies of patients with and without having ≥12 LN examined. Results: In the NCDB database, the percent of patients with stage II colon cancer who have ≥12 LN checked is much lower than current estimates. Non-Hispanic and Hispanic patients have similar LN examination rate, as do Blacks and Whites. 4% less men have ≥12 LN examined than women. Large differences exist among patients with different insurance statuses. Uninsured and Medicaid patients have much lower LN examination with ~80% of having <12 LN examined. CCPs have a lower rate of LN examination, with 7.4% more patients having <12 LN checked than CCCPs and 9.1% more than ACPs. When comparing frequency of those with <12 and ≥12 LN examined in a demographic, p<.05 in all comparisons. Conclusions: This largest, and most recent analysis of frequencies in patients with stage II colon cancer reflects a low rate of ≥12 LN being examined in those with stage II colon cancer. Rates of ≥12 LN being examined is greater in stage III colon cancer, however, there is a significant difference in survival when ≥12 LN are checked in stage II colon cancer as well. From 2004-2008 rates of LN examination increased, but rates of LN examination have since stagnated. Only around a quarter of patients have ≥12 LN examined; thus, this quality measure is only achieved in a minority of patients. [Table: see text]
Association of ongoing systemic inflammatory response (SIR) at diagnosis with lymph node retrieval and node positivity in patients undergoing surgery for colonic cancer.
Authors: Dolan Ross , McSorley Stephen Thomas , McMillan Donald C , Horgan Paul G.
Published: March 2017

550

Background: Prognosis in colonic cancer is largely based on pathological criteria such as TNM staging. However, there are deficiencies in this approach and the lymph node ratio (LNR) has been promoted as improving prediction of outcomes. In this context retrieval of lymph nodes and their examination is of considerable importance. Kennelly et al (World J Gastrointest Oncol 2016) in a recent study, in 331 patients undergoing surgery for colon cancer, reported an elevated LNR and lower lymph node retrieval in those patients with a SIR. In the present study these relationships were examined in a larger cohort of patients (n = 881). Methods: A prospectively maintained database of all patients undergoing elective curative colonic resection in our institution was examined. The SIR was measured by scores mGPS (C-reactive protein/ albumin), NLR (neutrophils/ lymphocytes), PLR (platelets/ lymphocytes) and LMR (lymphocytes/ monocytes) using standard thresholds mGPS (0,1,2), NLR ( ≥ 5), PLR ( ≥ 150) and LMR ( ≤ 2.4). Statistical analysis was carried out in SPSS using Independent Mann Whitney U and Kruskal-Wallis tests where appropriate. Results: Of the 881 patients included in the study, 467 (53%) were male, 414 (47%) female, the median lymph node count was 16 (0-48) and the median LNR in patients with positive nodal disease was 0.13 (0.02-1). There was a significant relationship between increased lymph node retrieval and laparoscopic surgery (p = 0.01), age < 70 (p = 0.021), lower BMI (p = 0.047), right sided tumours (p < 0.001), lymphatic invasion (p = 0.02) and neoadjuvant treatment (n = 0.001). There was a significant relationship between increased LNR and lower BMI (P = 0.022) and lymphatic invasion (p = 0.029). In contrast, lymph node retrieval was not associated with mGPS (p = 0.366), NLR (p = 0.523), PLR (P = 0.180) or LMR (p = 0.571). Similarly, LNR was not associated with mGPS (p = 0.313), NLR (p = 0.362), PLR (p = 0.592) or LMR (p = 0.263). Conclusions: The SIR as measured by a number of validated prognostic scores was not associated with either lymph node retrieval or positivity in patients undergoing elective surgery for colon cancer.
Demographic, clinical, and outcomes characteristics associated with screening colonoscopy in colorectal cancer patients.
Authors: Armstrong Samantha Ann , Shahda Safi , Sehdev Amikar
Published: March 2017

554

Background: Screening colonoscopy has well established role in CRC prevention. Factors associated with underutilization of screening colonoscopy, and how underutilization affects the CRC outcomes is unclear. We conducted a retrospective study with an aim to identify demographic, clinical and outcome characteristics associated with screening colonoscopy in patients with CRC. Methods: The Indiana Network for Patient Care (INPC) was used to identify patients diagnosed with CRC between 2001-2015. The INPC is the largest and longest tenured clinical data warehouse of the Indiana Health Information Exchange in the USA. Patient demographic (age, race, gender, median household income, insurance type, geographical location), clinical (BMI, year of diagnosis, stage, tumor location, CEA, surgery, chemotherapy, comorbidity) and outcome characteristics were obtained. Only patients who had colonoscopy prior to diagnosis were included, and divided those who received screening colonoscopy versus diagnostic colonoscopy. Chi-square was used for univariate analysis. Multivariate logistic regression was used to model the association of colonoscopy with overall mortality, and CRC-specific mortality. Results: A total of 1546 patients were identified, of which 361 (23.3%) and 1185 (76.6%) had screening and diagnostic colonoscopy, respectively. On univariate analyses, older age, female gender, Caucasian race, lower BMI and lack of insurance, were significantly associated with screening colonoscopy (P < 0.05). Additionally, patients receiving screening colonoscopy had higher likelihood to undergo surgery and receive chemotherapy (P < 0.05). Multivariate analyses adjusted for age, gender, race, surgery, chemotherapy and insurance status showed that screening colonoscopy (as compared with diagnostic colonoscopy) is associated with a 38% lower odds of overall mortality (adjusted OR = 0.62, 95% CI, 0.46-0.83, p < 0.001), and 68% lower odds of CRC-specific mortality (adjusted OR = 0.32, 95% CI, 0.19-0.51, p < 0.001). Conclusions: Screening colonoscopy is associated with decreased odds of overall and CRC-specific mortality and individuals with older age are more likely to receive it.
Correlation between total lesion glycolysis in 18F-FDG PET/CT and KRAS mutation and clinical features in patients with resectable colon cancer.
Authors: Hong Ji Hyung , Byun Jae Ho , Choi Eun Kyoung , Oh Jin Kyoung , Kim Ji-Hun , Lee YS
Published: March 2017

555

Background: Recently, novel metabolic parameters in 18F-FDG PET/CT such as total lesion glycolysis (TLG) and metabolic tumor volume (MTV) as well as maximum standardized uptake value (SUVmax) have been reported to be prognostic and be related with genomic aberration. We evaluated the prognostic role of these metabolic parameters and the correlation with clinical features in resected colon cancer. Methods: This study included 212 colon cancer patients who underwent surgical resection of stage II and III disease and conducted pre-treatment 18F-FDG PET/CT between February 2009 and December 2013. TLG, MTV of the primary tumors as well as SUVmax were analyzed according to clinical features including KRAS mutation, pre-treatment carcinoembryonic antigen (CEA) and recurrence free survival (RFS). Results: TLG was significantly higher in patients with right colon cancer than those with left colon cancer ( P = 0.015) and in patients with elevated CEA than those with normal range of CEA ( P = 0.034), while MTV and SUVmax were not correlated with cancer location and CEA level. KRAS mutation analysis using peptide nucleic acid-mediated real-time polymerase chain reaction clamping was conducted in 94 patients and forty-one (43.6%) patients showed KRAS mutation in tumor tissues. TLG was significantly higher in patients with mutated KRAS compared with in those with wild KRAS ( P = 0.021). CEA was significantly higher in patients with mutated KRAS than those with wild KRAS ( P-value = 0.024). CEA and TLG could predict KRAS mutation showing odds ratio 1.07 and 1.02 in the multivariate logistic analysis ( P-value = 0.024, 0.048). There was no difference of RFS between in patients with high TLG and in those with low TLG. Conclusions: Based on the result that TLG had a predictive role for KRAS mutation and was related with tumor location and CEA value, we suggested that TLG might reflect genomic alteration and other clinical features as well as tumor burden. It could be useful for differentiating different population of colon cancer and further study is clinically warranted.
Associations between regorafenib-induced adverse events (AEs) and efficacy in metastatic colorectal cancer (mCRC).
Authors: Wakatsuki Takeru , Shinozaki Eiji , Suenaga Mitsukuni , Nakayama Izuma , Matsushima Tomohiro , Osumi Hiroki , Ichimura Takashi , Ogura Mariko , Takahari Daisuke , Ozaka Masato , Chin Keisho , Yamaguchi Kensei
Published: March 2017

556

Background: It is occasionally recognized that, in molecular targeted therapy, target-specific AEs can surrogate its efficacy, such as skin toxicities and anti-EGFR antibodies. Because of multikinase inhibitor, regorafenib is involved in various kinds of adverse events; however, the clinical associations between AEs and efficacy remain unclear. The aim of this study is to reveal what AEs could surrogate efficacy of regorafenib. Methods: AEs were graded according to CTCAE ver. 4.0. We defined as “CRP increased”, if CRP increased more than 5 mg/dl during treatment compared with the baseline level. Time to treatment failure (TTF) and overall survival (OS) were estimated using Kaplan-Meier methods and compared by the log-rank test. Covariates which were significant in univariate analysis were included in multivariate analysis. Results: One-hundred and two patients were enrolled in this study. Almost all patients were PS 0-1 and received 160mg of regorafenib as an initial dose. The median TTF and the median OS were 2.0 and 8.0 months, respectively. Major AEs were Hand-foot skin reaction (HFSR) in 82.4% (≥Gr3:38.2%), Hypertension (HT) in 39.2% (16.7%), Rash in 23.5% (8.8%), Blood bilirubin increased (BBI) in 58.8% (2.9%), Thrombocytopenia in 48.0% (3.9%), Neutropenia in 20.5% (0%), and CRP increased in 46.1%. Regarding TTF, in univariate analysis, BBI, AST increased Gr0-1, neutropenia, absence of CRP increased, Diarrhea, HFSR, and Rash Gr0-2 were associated with longer TTF. In multivariate analysis, HFSR (HR 0.34 95%CI 0.19-0.63, p = 0.001) and Rash ≥Gr3 (HR 2.43 95%CI 1.13-5.21, p = 0.023) retained to be significant. With respect to OS, in univariate analysis, AST increased Gr0-1, ALT increased Gr0-1, neutropenia, absence of CRP increased, HFSR, and Rash Gr0-2 were associated with longer OS. In multivariate analysis, HFSR (HR 0.47 95%CI 0.24-0.91, p = 0.026), neutropenia (HR 0.54 95%CI 0.30-0.95, p = 0.032) and AST ≥Gr2 (HR 5.72 95%CI 2.11-15.63, p = 0.023) retained to be significant. Conclusions: HFSR and neutropenia might surrogate regorafenib efficacy in mCRC. Elucidation of the mechanisms of these AEs may help to understand which the pathway is the key role of regorafenib treatment in mCRC.
Relationship between primary tumor location and prognosis in metastatic colorectal cancer patients treated with irinotecan/5-FU/leucovorin (FOLFIRI).
Authors: Yu Qianqian , Qiu Hong , Zhang Mingsheng , Yuan Xianglin
Published: March 2017

557

Background: Clinical trials including CALGB/SWOG 80405 and FIRE-3 reveal differences in overall survival (OS) for metastatic colorectal cancer (mCRC) patients treated with targeted therapy based on primary tumor location. We assessed the impact of tumor location on prognosis in a prospective series of patients with mCRC received FOLFIRI in first-line therapy. Methods: Patients treated with FOLFIRI were consecutively recruited between November 2010 and December 2014. Follow-up information was updated in February 2016 when 77.3% of the patients were deceased. We defined the right-sided colon = cecum to transverse colon, left-sided colon = splenic flexure to sigmoid descending colon, rectum = rectosigmoid plus rectal cancer, respectively. We measured median survival using Kaplan-Meier plots and 2-year survival probability using life tables. Associations between tumor locations and treatment outcomes were estimated using a Cox proportional hazards model. Age and gender were included in adjusted Cox models to estimate the hazard ratio (HR) for death of rectal and left-sided tumors relative to right-sided tumors. Results: Right-sided cancer had a shorter median survival (13.5 vs. 20.4 months) and worse 2-year survival probability (28% vs. 39%) than left-sided and rectal cancers, however the difference was of no statistical significance no matter in unadjusted (HR = 1.002, 95% CI 0.635-1.581) or adjusted models (HR = 1.037, 95% CI 0.657-1.639). Conclusions: mCRC patients with right-sided colon got comparative survival benefit from FOLFIRI in first-line treatment to the left-sided colon and rectum. This result needs to be validated in studies with larger sample size. Clinical trial information: NCT01282658.
Evaluation of systemic inflammation-based prognostic scores in patients with advanced colorectal cancer receiving palliative pelvic radiotherapy (RT).
Authors: Dolan Ross , MacLeod Nicholas James , McSorley Stephen Thomas , Horgan Paul G. , Laird Barry , McMillan Donald C
Published: March 2017

558

Background: The presence of a systemic inflammatory response (SIR) in patients with advanced cancer is an increasingly recognised prognostic domain and is commonly assessed by the Glasgow Prognostic Score (GPS) and the Neutrophil Lymphocyte Ratio (NLR). However, little work has been carried out to evaluate their role in the field of palliative RT. The aim of the present study was to compare the prognostic value of the GPS and NLR in patients with advanced colorectal cancer receiving palliative pelvic RT. Methods: From a database of all patients undergoing RT in the West of Scotland (2010-2015) patients receiving palliative pelvic RT for colorectal cancer were examined (n = 175). Patients were excluded if they died within 30 days of treatment (n = 15). Demographic data, time from treatment to death/last clinic visit, medical comorbidities, tumour and RT location/dose, CRP, albumin, and differential blood counts were all recorded. GPS, mGPS and NLR were calculated and Cox regression analysis conducted in SPSS. Results: Of the remaining 160 analysed 85 (53%) were male and the median age was 77 (Range: 34-98). The most common clinical indications for palliative radiotherapy were pain (n = 78), bleeding (n = 71) and obstruction/tenesmus (n = 29). Medical comorbidities varied with the most common being hypertension (n- = 75), IHD (n = 36) and diabetes (n = 19). At the time of analysis 130 (81%) of the patients were dead with median survival of 9 months (Range: 1-62 months). On univariate survival analysis Male sex (p = 0.021), GPS (p = 0.015), mGPS (p = 0.028) and NLR ≥ 5 (p = 0.045) but not age > 75 (p = 0.059), Tumour Site (p = 0.637), Performance Status (p = 0.747), ASA (p = 0.525), Delivered Fractions of Radiotherapy (p = 0.062), Dose of RT (p = 0.486) and low Haemoglobin (p = 0.383) were significantly associated with poor survival. On multivariate analysis of the significant variable only male sex (HR: 1.59, 95%CI 1.07-2.36, p = 0.021) and the GPS (HR: 1.47, 95%CI 1.09-1.98, p = 0.011) remained independently associated with survival. Conclusions: In the palliative RT setting systemic inflammation based scores (GPS, mGPS and NLR) had prognostic value and the GPS had independent prognostic value.
Meat and fish consumption and risk of colorectal adenomas in Korea.
Authors: Yang Sun Young , Doo Eun Young , Kim Young Sun , Lee Jung Eun , Youn Jiyoung , Song Ji Hyun , Yim Jeong Yoon , Lim Sun Hee
Published: March 2017

559

Background: Consumption of red meat and alcohol are known risk factors for colorectal cancer. Colorectal adenomas are considered precursors to colorectal cancer through adenoma-carcinoma sequence. The identification of modifiable risk factors for colorectal adenoma contributes to prevent colorectal cancer from progressing. Many studies have suggested that high red meat or processed meat intake is associated with an increased risk of colorectal adenoma. However, the effect of high fish intake on colorectal adenoma has been insufficient in epidemiological studies. The aim of this study is examine the relationship between meat and fish intake and the risk of colorectal adenoma. Methods: The study enrolled participants who visited Seoul National University Hospital Healthcare System Gangnam Center from May to December, 2011. All participants underwent screening colonoscopy and completed validated food frequency questionnaire. The study sample included 414 adenoma patients, 142 advanced adenoma patients and 1160 polyp-free controls. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between meat and fish and colorectal adenoma using multivariate logistic regression. Results: The intake of total meat, red meat, poultry or processed meat showed no clear association with risk of colorectal adenoma or advanced adenoma. A significant negative association between fish intake and risk of advanced adenoma (OR = 0.51, 95% CI = 0.27 – 0.95, p for trend = 0.0281) after adjusting for confounders such as age, BMI, family history of colorectal cancer, alcohol consumption, smoking status, diabetes, total energy intake, fiber, vegetable/fruit and red meat intake. Conclusions: In conclusion, this study showed no clear relationship between the incidence of colorectal adenoma/advanced adenoma and meat intake. Although, high fish intake and incidence of advanced adenoma showed a significant inverse association in Korean.
A phase II Study of FOLFOX versus POF (paclitaxel plus FOLFOX) versus IP PAC (intraperitoneal paclitaxel) plus FOLFOX as a first-line treatment in advanced gastric cancer (AGC): A feasibility analysis.
Authors: Lin Rongbo , Zhao Shen , Li Hui , Liu Jie , Fan Nanfeng
Published: March 2017

56

Background: Double regimens are commonly accepted for AGC in East Asia. However, triple regimens are recommended in west countries. POF regimen (a modified DCF reported in 2007, 2008, 2009, 2010 ASCO) appeared to be of good efficacy and was well tolerated in patients with AGC. Intraperitoneal paclitaxel showed high local concentration in abdominal cavity and low systemic toxicity. The aims of this study were to find out if the triplet POF was more effective with manageable side effects and IP PAC in combination with FOLFOX had higher local control rate and manageable systemic toxicity than doublet FOLFOX in AGC. Methods: The patients with AGC were randomized to three group. The FOLFOX regimen consisted of oxaliplatin 85 mg/m2, levoleucovorin 200 mg/m2, and 5-FU 400 mg/m2 bolus on day 1, then 5-FU 2400 mg/m2 continuous infusion over 46 hours. The POF regimen consisted of a 3-hour infusion of paclitaxel 135 mg/m2, followed by FOLFOX omitted 5-FU bolus. The IP PAC plus FOLFOX regimen consisted of paclitaxel 80 mg/m2 intraperitoneally plus FOLFOX. Every 14 days repeated for all three regimens. Up to 9 cycles of treatment were administered, followed by S-1 until disease progression Results: From 4th November 2015 to 10thJune 2016, 21 patients with ECOG PS 0-1 were assigned for the study. Grade ¾ toxicities, in the FOLFOX group (n = 7), neutropenia and nausea was one respectively; in the POF group (n = 9); neutropenia were two, stomatitis, nausea, vomiting, and fatigue was one respectively; in the IP PAC plus FOLFOX group (n = 5), neutropenia and fatigue was one respectively. No treatment-related death occurred. Median progression free survival and overall survival were 68 days and 194 days in FOLFOX group, 128 days and 282 days in POF group, 89 days and 178 days in IP PAC plus FOLFOX group. Conclusions: This pilot analysis showed three regimens including IP PAC plus FOLFOX had good safety profits. The POF group seemed to have better PFS and OS than the other two groups. This ongoing phase II study is feasible. Clinical trial information: NCT02845908.
Community that pays together stays together: Sharing of resources for colorectal cancer screening and treatment of the underserved population.
Authors: Dowd Katie E , Mishra Aparajita , Marsh Michelle , Cox Dawn , Aydin Nail , Yang Derek , Misra Subhasis
Published: March 2017

561

Background: Bridging disparities to increase colorectal cancer (CRC) screening and treatment can be expensive and time consuming. This insurmountable cost often limits care; however, for every $1 spent on cancer screening $22.37 is saved on treatment costs and economic benefits. By finding cancer through free screening initiatives for the public, a new problem arises of how to fund further treatment. Methods: Project goals are to increase screening rates and knowledge about CRC and screening in our medically underserved region. The project provides screening at no cost, but these unfunded patients do not have coverage to treat their cancer diagnosis. By establishing partnerships with home health organizations, hospital CEOs, federally qualified health centers, locally elected officials, department of public health employees, and healthcare professionals our project has navigated patients through screening and treatment free of charge by encouraging community sharing of resources. Community relationships have been nurtured by utilizing quarterly program meetings, educational outreach for providers with CME credit, and cancer symposiums. This outreach provides an open forum to ask for feedback and coordinate care for the community with a primary focus on population healthcare management. Results: In addition to the many precancerous lesions removed, two cases were identified that needed further cancer treatment. The first patient did not qualify for county indigent clinic care. One private hospital waived the facility fees and we waived the surgeon fees, and the local cancer center agreed to cover adjuvant chemotherapy costs. Another patient was navigated to a local indigent care clinic, with CT scans paid by another nonprofit organization. This patient received surgery at no cost from the surgeon or hospital. These illustrations reflect community involvement in sharing cost for the uninsured. Conclusions: Utilizing cost and resource sharing through patient navigation can lessen the financial burden of caring for uninsured patients. By focusing on community relationships, our project is overcoming limitations to provide comprehensive care for patients.
Predictors of circulating tumor-derived methylated BCAT1 and IKZF1 DNA in colorectal cancer patients.
Authors: Symonds Erin L , Pedersen Susanne Kartin , Murray David , Baker Rohan , Young Graeme P
Published: March 2017

567

Background: Blood tests detecting circulating tumor-derived DNA (ctDNA) are being developed for colorectal cancer (CRC) screening and monitoring. However, the underlying tumor biology resulting in circulating DNA is not well understood. This study aimed to elucidate tumor features associated with methylated BCAT1 and IKZF1 DNA in blood as well as patient demographics that predict biomarker appearance. Methods: 129 people with invasive CRC had blood collected prior to surgery. Patient sociodemographic factors were recorded. Extracted circulating cell-free DNA was assayed for methylated BCAT1 and IKZF1. Patient factors and tumor features including location, size, depth of invasion (T stage), degree of differentiation, vascularity, lymphatic and perineurial invasion, lymph node involvement and presence of metastasis were compared with blood test results using multivariate logistic regression analysis. Results: The distribution of CRC stages I to IV were 34, 43, 41 and 11, respectively and 72 (56%) were blood positive for methylated BCAT1/IKZF1. Positivity was associated with distally located tumors and a higher T stage (Table). Gender, age, BMI, race, smoking and medications were not associated with blood positivity rates, but increased alcohol intake ( > 7 drinks/week, n = 31) was associated (OR 5.7, 95% CI 1.1-28.7, p = 0.036). Conclusions: The strongest predictor for appearance of ctDNA was invasion depth of the tumor. Demographic features did not influence the positivity rate of the BCAT1/ IKZF1 CRC blood test, strengthening the validity of this blood test for CRC screening and monitoring in the general population. [Table: see text]