bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of MRI or PET fusion in radiotherapy treatment planning on the pathological complete response rate in rectal adenocarcinoma.
Authors: Rana Zaker Hamid , Hong Robert , Han Joon , Chen Isaac , Nurhussien Mohammed , Nasr Nadim Munir 
Published: February 2017

523 Background: A pathological complete response rate of 10% to 30% has been noted to occur following preoperative chemoradiation with CT-based treatment planning in patients with rectal cancer. Fusion of the treatment planning CT with other imaging modalities like MRI or PET may help identify tumor location and improve tumor coverage. This retrospective study sought to evaluate the effect of adding MRI or PET imaging to CT-based treatment planning and its impact on pathological complete response rates in patients with rectal cancer. Methods: A retrospective analysis was performed on 39 patients, who received neoadjuvant chemoradiation for rectal adenocarcinoma from February 2009 to September 2013. Patients were divided into two groups. The first group was treated using CT-only based treatment 3D-Conformal or IMRT planning (n=9) and the second was treated using either PET or MRI fusion with the simulation CT scan (n=30). Patients were treated to a total of 5,040 cGy in 28 fractions. Pathological complete response rates (ypT0N0M0) were assessed using postoperative pathologic reports following resection. Results: 39 patients with a median age of 62 received preoperative chemoradiation with an interval to surgery ranging from 34-162 days and a median of 70 days. Patients treated with PET or MRI fusion treatment planning showed a complete pathological response rate at the primary site of 60% and a complete lymph node pathological response rate of 70.83% compared to 22.22% at the primary site and 66.66% at lymph node sites in patients with CT-only treatment planning. In patients treated using MRI or PET fusion, middle rectal cancer showed the best complete pathological response rate at 80%, followed by lower rectal cancer at 41.66%, and upper rectal cancer at 37.5%. Conclusions: Although the sample size was small, utilization of MRI or PET fusion resulted in a higher pathological complete response rate when compared to CT-only based treatment planning, especially in middle rectal cancers. Further studies are needed to accurately identify those patients with a complete pathologic response which may ultimately alter their treatment course.
Measuring compliance to capecitabine in colon cancer: A comparison of administrative data and medical records.
Authors: Amlani Adam , Kumar Aalok , Cheung Winson Y. 
Published: February 2017

531 Background: Studies of administrative data indicate that compliance with oral anti-neoplastic agents, including capecitabine, is suboptimal. Using a population-based cohort of colon cancer, our aim was to evaluate the proportion of patients deemed non-compliant that actually had a reasonable indication for not adhering to their prescribed oral systemic therapy. Methods: Consecutive patients diagnosed with stage III colon cancer from 2008 to 2010, referred to any 1 of 5 regional cancer centers in British Columbia, Canada, and who initiated at least 1 cycle of oral adjuvant capecitabine within 12 weeks of curative resection were reviewed. Administrative data from the provincial oncology pharmacy database were analyzed to assess for non-compliance, which was defined as any prescription refill delays of >/=1 week from the end date of the preceding cycle. Electronic medical records were abstracted to examine the factors, if any, which contributed to non-compliance. We compared administrative vs. medical record data to determine the level of concordance and the appropriateness of non-compliance. Results: We included 752 patients: median age was 70 years (IQR 35-87), 56% were men, and 86% had ECOG 0/1. Administrative data showed that 413 patients were non-compliant: 230 (56%) and 183 (44%) had 1 and >/=2 late refills, respectively. In this group, a total of 2095 cycles of capecitabine were delivered among which 688 (33%) treatment delays occurred. No differences in baseline characteristics were observed between individuals who were compliant and those who were not (all p>0.05). Of the 688 prescription delays that were ascertained from administrative data, medical records demonstrated that 30 (4%) were misclassified. From the remainder, the majority were attributable to valid reasons, including: 339 (49%) toxicities necessitating time off therapy; 170 (25%) physician discretion; 40 (6%) travel requiring adjustment to treatment schedule; and 6 (1%) patient refusal. Only 103 (15%) cases were considered as true non-compliance. Conclusions: Using administrative data alone to measure oral drug compliance without corroborating with medical records may overestimate the degree of non-adherence.
Changes in the inflammatory microenvironment in premalignant colonic adenomatous polyps: Evidence for immunosurveillance?
Authors: Mansouri David , Park James Hugh , Orange Clare , Crighton Emilia M. , Horgan Paul G. , Mcmillan Donald C. 
Published: February 2017

535 Background: The majority of colorectal cancers develop through the adenoma-carcinoma sequence. Recently, the host inflammatory response has become recognized as a key determinant of outcome. In particular, a pronounced peri-tumoral local inflammatory infiltrate identifies those with a better outcome. The present study aimed to characterize the local inflammatory response in pre-malignant colorectal adenomatous polyps. Methods: Patients with adenomatous polyps removed at colonoscopy as part of a population FOBt screening program were identified from a prospectively maintained database. All polyps were greater than 1cm. Whole slide immunohistochemistry was performed to assess intraepithelial T-cell (CD3+), cytotoxic T-cell (CD8+) and macrophage (CD68+) infiltrate. Inter-observer agreement for assessment of inflammatory cell infiltrate was good or better for CD3+, CD8+ and CD68+staining (Kappa 0.66, 0.66, 0.79 respectively). Results: A total of 207 adenomatous polyps, 107 high-grade (HG), 100 low-grade (LG), from 134 patients were included. Median age was 65 years, 33 (25%) were female and 15 (11%) were taking regular aspirin. Comparing HG and LG polyps, there were more older and female patients in the HG group (p<0.05). There was no difference in location (p=0.222), macroscopic morphology (p=0.445) or aspirin (p=0.377) use between groups. Microscopically, HG polyps were more likely to contain a villous component than LG polyps (65% vs 50%, p<0.05). Overall, high levels of CD3+, CD8+ and CD68+ infiltrate were observed in 68%, 25% and 72% of polyps respectively. Both CD3+ (74% vs 61%, p<0.05) and CD8+ (37% vs 13%, p<0.001) infiltrate was higher in HG polyps compared to LG polyps. There was no association with polyp grade and CD68+infiltrate (74% vs 70%, p=0.540). Conclusions: An increase in local T-lymphocytic infiltrate, but not macrophage infiltrate was identified with progression from low-grade to high-grade dysplasia. This would suggest a specific response to early disease progression confirming increased immunosurveillance. Therefore, such early stage disease may amenable to immunomodulatory treatment.
Utility of invasive staging procedures in patients (pts) with localized esophageal cancer (EC).
Authors: Giever Thomas A. , Ranade Arjun , Thomas James P. , Ritch Paul S. , Haasler George , Gasparri Mario , Johnstone David , Gore Elizabeth , Johnstone Candice Aitken , Dua Kulwinder , Khan Abdul , Oh Young , George Ben 
Published: February 2017

54 Background: Definitive treatment for localized EC involves surgery alone or tri-modality therapy (TMT-chemotherapy, radiation, and surgery). TMT is administered to pts with clinical T2 or higher and lymph node (LN) positive ECs. Standard staging includes Computerized Tomography (CT)/Positron Emission Tomography (PET) imaging and Endoscopic Ultrasound (EUS). We investigated whether performing an EUS altered treatment decision in localized EC pts where a combination of imaging and clinical symptoms suggested the need for TMT. Methods: We performed a retrospective review to identify pts with localized EC who had their staging work up and treatment at the Medical College of Wisconsin between 2003 and 2012. Relevant clinical information was collected through review of the electronic medical record. Results: We identified 65 pts; median age at diagnosis was 62 years, 49 (75%) were male, and 56 (86%) were Caucasian. Histology was adenocarcinoma in 48 (74%) pts with 21 (44%) having background Barrett’s esophagus. Common presenting symptoms included dysphagia (83%), weight loss (73%), and odynophagia (25%). Staging evaluation included CT, PET, and EUS in 100%, 98%, and 89% of pts respectively. EUS staging results are in the table below. Dysphagia was reported by 67% of T1, 80% of T2, 84% of T3, 50% of T4, and 100% of Tx pts; 70% of pts with dysphagia were node positive by EUS. PET positive primary tumors/LNs were found in 89%/29% of all pts and 89%/33% of pts with dysphagia. Of the pts with PET positive LNs, 68% had node positive disease on EUS. Eighteen (28%) pts had both dysphagia and PET positive LNs, none with T1-2N0 staging by EUS; 36 pts had dysphagia and PET negative LNs, 7 (19%) with T1-2N0 staging by EUS. Among those 7 pts, 4 underwent surgery (1 pt-pT3N1aMx; 3pts-pT1bN0Mx). Conclusions: Localized EC pts with both dysphagia and PET positive LNs are candidates for TMT even in the absence of EUS staging. The role of EUS in this population may be limited to investigating adjacent organ invasion or confirmation of LN involvement. With improving PET capabilities, the role of EUS in this pt population needs to be studied prospectively. [Table: see text]
Real-world treatment patterns and the uptake of biologics in elderly medicare patients with metastatic colon cancer.
Authors: Mullins C. Daniel , Bikov Kaloyan A. , Seal Brian S. , Hung Anna , Hanna Nader 
Published: February 2017

540 Background: Metastatic colon cancer (mCC) patients may receive multiple lines of treatment (Tx1, Tx2, etc.) consisting of one or more cytotoxic (CYT: 5FU/LV, oxaliplatin [OX], irinotecan [IRI]) and biologic (BIO: bevacizumab [BEV], cetuximab [CET], panitumumab [PAN]) drugs. The National Comprehensive Cancer Network (NCCN) provides evidence-based Tx recommendations for each line. The objective of this study was to examine real-world clinical practice patterns between 2002 and 2010. In particular, we compared the most common regimens across Tx lines and how Tx patterns changed over time. We also documented the uptake and use of new BIOs. Methods: We used population-based SEER-Medicare data to determine Tx1, Tx2, and Tx3 regimens of 4,616 mCC patients (the median age at diagnosis was 78) diagnosed in 2003-2009 and followed through 2010. We will use an algorithm previously developed by us to identify regimens. Results: The most common CYT backbone in Tx1 was OX (51% of patients) followed by 5FU/LV (30%). In comparison, IRI was a preferred choice in Tx2 (65%) and Tx3 (31%). In 2003, the most common Tx1 regimens were 5FU/LV- (56%) and IRI-based (35%). 5FU/LV and IRI use decreased to 22% and 9% respectively in 2009, while OX use increased from 7% in 2003 to 63% in 2009. In 2004, the FDA approved BEV for Tx1. BEV’s share increased from 9% in 2004 to 53% in 2005. BEV was used in 9% of Tx2 regimens in 2004 and 46% in 2005. CET was approved in 2004. CET was used in less than 5% of Tx1 regimens in any year up to 2010. CET use in Tx2 increased from 19% to 27% between 2005 and 2007, and declined to 23% in 2010. The FDA approved PAN in September 2006 for treatment after failure of CYT-based regimens, i.e., primarily in Tx3 and beyond. Only 350 (8%) of patients received Tx3, and of these 59 (17%) received PAN without a CYT backbone. One in three Tx3 regimens consisted of biologics only (54% CET, 43% PAN). Conclusions: This study used SEER-Medicare registry data to examine and document real-world clinical practice patterns in treatment of elderly mCC patients between 2003 and 2010. We observed that as new biologic agents were introduced to the market, variations in the combinations and the number of treatment have significantly and rapidly changed.
Does post-treatment surveillance imaging improve outcomes in patients with locally advanced rectal cancer?
Authors: Wahl Michael , Haas-Kogan Daphne A. , Anwar Moshiur Mekhail , Venook Alan P. 
Published: February 2017

548 Background: The optimal post-treatment surveillance strategy for pts with rectal cancer is undefined. Trials examining surveillance with serial CEA measurements and/or imaging for colorectal cancer have yielded conflicting results, and no prospective trials have been done specific to rectal cancer pts. In the absence of data, reputable guidelines advocate serial chest, abdomen and pelvic imaging, CEA and colonoscopy after definitive treatment of rectal cancer. The rationale is to identify recurrence before it is symptomatic: if local, to avoid morbidity and if distant, because of the possibility of curative therapy. However, frequent imaging raises concerns regarding radiation exposure, consequences from false-positive findings, and cost. Methods: We performed a retrospective cohort study of patients with stage II/III rectal cancer treated definitively with neoadjuvant chemoradiation followed by surgical resection over the past 10 years. CEA, imaging studies and colonoscopies were recorded for all pts with follow-up of at least 6 months, along with clinical endpoints of locoregional recurrence, development of distant metastases, nature of subsequent therapies, and survival. Results: 55 pts with complete follow-up data were identified (median follow-up, 3.2 years). Surveillance was performed with imaging, CEA and colonoscopy in 89%, 72% and 49% of pts, respectively. 6 local recurrences were identified (11%): two were diagnosed via surveillance imaging, 3 underwent surgery with curative intent, with one patient with no evidence of disease at last follow-up. In contrast, 13 pts (24%) developed distant metastases (6 liver, 5 lung, 2 diffuse metastases), of which 9 were detected on surveillance imaging, 7 underwent therapy with curative intent, and 6 had no evidence of disease at last follow-up. There were 8 false-positive imaging results, 2 of which resulted in unnecessary surgery. Conclusions: Our findings suggest that post-treatment surveillance imaging is useful for detecting oligometastatic disease amenable to curative therapy, but may be less so for locoregional recurrences. Prospective data is needed to further assess the utility of post-treatment imaging in this population.
Identifying patients at high risk for colorectal cancer: A pilot study of colonoscopy in patients with rectal bleeding in a low-income country.
Authors: Alatise Olusegun Isaac , Bello Ibrahim S. , Komolafe Akinwunmi O. , Adekanle Olusegun , Kingham T. Peter 
Published: February 2017

560 Background: Colorectal cancer (crc) is one of the most common cancers worldwide. There is an increasing incidence in low and middle income countries (LMICs). Patient outcomes are poor due to a lack of screening programs. Timely and efficient referral leading to earlier diagnosis of crc is imperative to improve survival. This study was initiated to determine the value of colonoscopy in patients with rectal bleeding for diagnosing crc in Nigeria. Methods: This is a prospective study of patients older than 45 years that present with rectal bleeding at 5 primary health care facilities in Ile-Ife, Nigeria. Patients were enrolled when they were referred for colonoscopy at the Endoscopy unit of Obafemi Awolowo University Teaching Hospitals. Data obtained included the socioeconomic, clinical, anthropometric, colonoscopy and histopathological parameters. Results: In this interim analysis, 68 patients were recruited into the study. The median age was 58.5 years (range 45-89 years). Median duration of rectal bleeding was 6 months (0.25 -360 months). Fifty six (82.4%) patients had seen a doctor regarding their rectal bleeding prior to the current episode for which they were referred. Changes in bowel habits and weight loss were found in 29 (42.6%) and 30 (44.1%) patients respectively. Crc was found in 14 (21%) patients and polyps in 11 (16.2%) patients. Hemorrhoids were found in 68% of patients. Of the 14 patients with crc, 10 had stage II or III disease (71.4%). Weight loss occurred in 14 (100%) of patients with crc, compared to 16 (30%) of patients without crc (p<0.0001). Conclusions: Given the high specificity of rectal bleeding in predicting the possibility of occurrence of colorectal cancer and polyps, this symptom may be used to select patients needing screening in resource poor settings. [Table: see text]
Preoperative serum microRNA-203 as a novel prognostic and metastasis-predictive biomarker in patients with colorectal cancer.
Authors: Toiyama Yuji , Hur Keun , Okugawa Yoshinaga , Boland C. Richard , Goel Ajay 
Published: February 2017

564 Background: Distant metastasis is the major causes of death in colorectal cancer (CRC) patients. Epithelial-mesenchymal transition (EMT) is a key process that converts polarized immotile epithelial cells into motile, invasive mesenchymal cells, enabling cancer cells to gain stem cell characteristics and an aggressive malignant phenotype such as metastasis. Mir-203 has been shown to directly suppress EMT activators such as ZEB2 and SNAI1/2. However, in spite of the key functional role of miR-203 in cancer metastasis, no previous studies have investigated the clinical significance of miR-203 in patients with CRC. Methods: To examine whether CRCs secret miR-203 in vitro and vivo,we first determined extracellular miR-203 levels in CRC cell culture media. Then, we quantified miR-203 levels in serum from mice with or without metastasis. Next, we investigated miR-203 expression in 58 pairs of primary CRC (pCRC) and corresponding matching liver metastasis (LM), as well as 186 serum and 154 matched tissue specimens from CRC patients. Results: HT-29 cells released miR-203 into culture media, which was dependent on cell number and duration of culture. In addition, high serum miR-203 levels were observed in mice with liver metastasis compared to control animals (p=0.0181). Mir-203 expression was significantly upregulated in LM compared to matching pCRC tissues (p=0.0002). Serum miR-203 was significantly upregulated in a tumor stage-dependent manner (p=0.0070), and high miR-203 expression was associated with poor survival in CRC patients (p<0.0001). In contrast to serum, no significant association between miR-203 expression in CRC tissues and clinicopathological findings was recognized. High serum miR-203 expression was an independent risk factor for poor prognosis (HR=2.1) as well as metastasis to lymph nodes (OR=2.5), liver (OR=6.2), peritoneum (OR=7.2), and distant organs (OR=4.4), respectively. Conclusions: High levels of serum miR-203, which may be derived from several metastatic sites, are associated with poor survival and metastasis, suggesting it is a promising non-invasive prognostic and metastasis-predictive biomarker in patients with CRC.
Genomic analysis and personalized cancer therapy for metastatic colorectal cancer.
Authors: Dang Rajan Paul , Ang Celina , Holcombe Randall F. , Sung Max W. , Cagan Ross L. , Schadt Eric , Posner Marshall R. , Donovan Michael J. , Winder Lewis A. , Kahn Adnan , Camille Nadia , Davis Claire R. , Smibert Peter , Misiukiewicz Krzysztof 
Published: February 2017

568 Background: Standard approaches in cancer research identify new therapies based on observed benefit to average populations but without emphasis on individual patients whose responses can vary considerably. Also, targeted therapies rarely account for the genomic complexity of patient tumors; the result is poor efficacy and rapid resistance. We would identify drugs or drug cocktails that (1) target the details of an individual’s tumor and (2) account for its complexity. Models using the fruit fly Drosophila represent a potential new paradigm in cancer therapy. We have developed fly models that can include up to 10 of a patient’s tumor’s driver mutations; the result is an inexpensive drug-screening platform to identify drug cocktails through empirical screening. Methods: Patients with metastatic CRC who have progressed or become intolerant to fluoropyrimidines, oxaliplatin, irinotecan, avastin, and (if KRAS wild-type) EGFR inhibitor therapy. Mutations identified by deep DNA and RNA sequencing of individual tumors are screened for tumor drivers, which are then incorporated into the “personal” Drosophila model and tested against a library of FDA approved drugs. Fly mortality is used as a surrogate for toxicity; improvements in tumor mutation-linked eye and/or wing abnormalities serve to quantify efficacy. This allows rapid and parallel screening of up to 800 drugs and subsequent drug combinations. The most efficacious and least toxic combinations are presented to a multidisciplinary tumor board of experts, who will then select the best therapeutic option for the patient. Results: To demonstrate that the personalized Drosophila model approach is superior to the current standard, regorafenib, which performed best in CRC with a 10% response rate (RR) against placebo in a phase III trial. Using the 10% RR as a benchmark, we will apply a sequential Bayesian method for 50 MTC patients enrolled to receive personalized treatment to demonstrate that this approach has greater efficacy, or at minimum, substantially similar efficacy with reduced toxicity. Conclusions: To demonstrate that personalized cancer therapy is superior to the current standard and is an effective therapy worth exploring for other cancers too.
Genomic alterations to predict response to irinotecan-based chemotherapy in metastatic colorectal cancer.
Authors: De La Fouchardiere Christelle , Jiang Xiaojun , Pissaloux Daniel , Seigne Christelle , Wang Qing , Desseigne Françoise , Fondrevelle Marie-Eve , Cassier Philippe Alexandre , Attignon Valéry , Combaret Valérie , Pérol David , Tredan Olivier , Blay Jean-Yves 
Published: February 2017

586 Background: No evidence exists concerning the superiority of oxaliplatin versus irinotecan-based chemotherapy for metastatic colorectal cancer. The choice is currently made by the clinicians according to awaited toxicity and association with targeted therapy. The correlation between response to chemotherapy (oxaliplatin and irinotecan containing regimens) and genomic alterations was investigated in metastatic colorectal cancer patients included in the ProfiLER protocol (NCT 02029001). Methods: From 03/2013 to 03/2014, 62 patients with metastatic colorectal cancer were included in the ProfiLER trial. Tumor samples were analyzed for mutations/insertions/deletions and copy number variations using target high-throughput sequencing (NGS) and comparative genomic hybridization array (CGH). Clinical data were collected retrospectively. We defined irinotecan and/or oxaliplatin responders as patients having CR, PR, SD as best response and non-responders as those having PD as best response. Results: 50/62 tumor samples fulfilled DNA quality requirements. CGH was feasible in 40 patients (64.5%). Among these 40 patients, 36 received oxaliplatin and irinotecan. None of the genomic alterations correlated to response to oxaliplatin. Conversely, analysis of the CGH and NGS data revealed different genomic alterations of tumors in patients receiving Irinotecan, allowing the separation between Irinotecan responders (IriR, n=27) and non-responders (IriNR, n=9) (Table). Conclusions: Specific genomic alterations of CRC cells seem to be associated with responses to systemic combination Irinotecan based-chemotherapy, including high GI, specific chromosomal gains, and tyrosine kinases mutations. A prospective validation of the CGH profile is planned and definitive results will be presented at the meeting. Clinical trial information: NCT 02029001. [Table: see text]