bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anal cancer outcomes in patients treated with intensity modulated versus 3-dimensional chemoradiotherapy.
Authors: Cooper Benjamin Thomas , Grew David , Bitterman Danielle , Sanfilippo Nicholas , Du Kevin Lee 
Published: February 2017

662 Background: Combined chemoradiotherapy (CRT) has been successful in both tumor eradication and colostomy prevention in patients with squamous-cell carcinoma of the anal canal. Unfortunately, CRT can be toxic with high rates of acute gastrointestinal and skin toxicity. This can necessitate treatment interruptions, prolonging therapy, possibly leading to loss of local control. In RTOG 0529, intensity modulated radiation therapy (IMRT) decreased the rate of treatment interruption compared to historical controls. We aim to compare toxicity and outcomes in patients treated with CRT based on radiation technique. Methods: We retrospectively reviewed 107 consecutive patients, 39 HIV+, 68 HIV-, who underwent definitive CRT for anal cancer at a single institution between 2004 and 2013. Overall survival (OS), colostomy-free survival (CFS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) were analyzed. Chi-square test was used to compare frequencies and t-test was used to compare means. Kaplan-Meier survival was calculated and differences were evaluated by Log-rank statistic. Results: Median follow-up was 15 months. Radiation technique was IMRT in 60% of patients with the remainder treated with 3-dimensional conformal radiation therapy (3D). Dose to the draining lymph nodes was higher in patients treated with IMRT (mean dose 40 Gy vs. 32 Gy, p < 0.001). Fewer patients had a greater than 10 day treatment break in IMRT cohort than the 3D cohort (21% vs. 43%, p = 0.028). Three-year OS (91% vs. 47%, p < 0.001) and DMFS (88% vs 64%, p= 0.033) were improved in patients treated with IMRT. There was no significant difference in acute GI or skin toxicity. There was no difference in stage, number of chemotherapy cycles and dose reductions, growth factor support, transfusion necessity, hospital admission, LRFS, sphincter function preservation, or CFS. Conclusions: In this cohort, patients treated with IMRT had better OS and DMFS than patients treated with 3D. Higher radiation doses to the draining lymph nodes and fewer prolonged treatment breaks may contribute to improved outcomes in patients treated with IMRT. Further studies are necessary to establish the etiology of this difference in outcomes.
Matched pair analysis of sequential short course radiotherapy and FOLFOX chemotherapy as preoperative therapy for rectal cancer compared to neoadjuvant long course chemoradiotherapy.
Authors: Youssef Fady , Markovina Stephanie Subasic , Khwaja Shariq S. , DeWees Todd A. , Hunt Steven R. , Tan Benjamin R. , Myerson Robert J. , Parikh Parag J. , Olsen Jeffrey R. 
Published: February 2017

665 Background: A recently completed institutional phase II trial evaluated near-total neoadjuvant therapy (nTNT) for locally advanced rectal cancer using short course radiotherapy (SCRT) followed by four cycles of FOLFOX prior to total mesorectal excision (TME). A matched pair analysis is presented to compare clinical outcomes for nTNT with conventional chemoradiotherapy (CRT), TME, and postoperative chemotherapy (CT) for patients treated at our institution. Methods: 80 patients with cT3-4N0-2M0-1 rectal adenocarcinoma planned for resection of all tumor enrolled on a phase II study of preoperative SCRT (25 Gy to the involved mesorectum, 20 Gy to elective nodes, in 5 fractions) followed by four cycles of mFOLFOX6 before TME, with 6-8 cycles of adjuvant FOLFOX suggested. 69 patients with cM0 disease comprised the study cohort for this analysis. Patients treated with conventional CRT, followed by TME and adjuvant CT (63% ≥4 cycles adjuvant FOLFOX) were identified and matched 2:1 for exact cTNM stage. Kaplan-Meier with log-rank analysis was used to compare local control (LC), distant metastasis free survival (DMFS), disease free survival (DFS), and overall survival (OS), and two-tailed Mann-Whitney and Chi-squared tests used to compare cohort characteristics. Results: Median follow-up was 26 and 49 months for the study and control groups, respectively. Median age (57 vs. 55 years, p = 0.98) and distance from the anorectal ring (6 vs. 5 cm, p = 0.16) were similar for study and control groups, respectively. Pathologic complete response (pCR) and T-downstaging rates were 30% vs. 23% (p = 0.26) and 75% vs 50% (p = 0.001) in the study and match cohort, respectively. Actuarial 2-year LC (97% vs. 98%, p = 0.69) and OS (100% vs. 95% at 2 years, p = 0.57) were similar between the study and control groups, respectively. Two-year DMFS (94% vs. 80%, p = 0.016) and DFS (94% vs. 80%, p = 0.027) were significantly better in the study cohort. Conclusions: Controlling for institutional bias, exact cTNM stage, and tumor location, nTNT resulted in increased T-downstaging, superior DMFS and DFS, and similar LC and OS compared to conventional CRT.
Detection of actionable oncogene drivers alterations in HER2-amplified gastric cancer by next generation sequencing.
Authors: Gomez-Martin Carlos , Pazo Cid Roberto A. , Salud Antonieta , Fonseca Paula J. , Leon Ana , Galan MaCarmen , Visa Laura , Rivera Fernando , Alsina Maria , Plaza Carlos , Angulo Barbara , Hernandez Prieto Susana , Dominguez Carolina , Rodriguez Garcia Margarita , Del Valle Elena , Fernandez Soledad , Rojo Federico , Cuatrecasas Miriam , Lopez-Rios Fernando 
Published: February 2017

67 Background: HER2 amplified cases are the only subset of gastric carcinoma (GC) patients with an approved targeted therapy (≈20%). In GC it is still unknown if there is a mutually exclusive pattern of mutations in major driver oncogenes. We performed a systematic search for targetable oncogenes in a cohort of HER2 amplified GC patients. Methods: 53 Formalin-fixed paraffin embedded samples from HER2 amplified GC patients (43 tumor and 10 normal samples) were selected for next generation sequencing (NGS). Before DNA extraction a macrodissection procedure was performed to guarantee at least 30% tumor in all cases. DNA samples were sequenced using the Ion Torrent Personal Genome Machine (PGM) sequencing platform (Life Technologies, Carlsbad, CA, USA). The Ion AmpliSeq Cancer Hotspot Panel v2 was used. This panel encompasses more than 2800 mutational hotspots of 50 oncogenes and tumor suppressor genes. Data were processed using the Ion Torrent platform-specific pipeline software Torrent suite v4.2. Moreover, sequencing data were analyzed with Ion Reporter software 4.2 to detect any copy number alteration of the genes included in the panel. Results: We successfully sequenced all samples. We identified 89 mutations in 12 genes (range from 1 ~ 9). The most frequent significant mutations included TP53 mutations (30), PI3KCA (3), SMAD4 (3), CDKN2A (4), CTNNB1 (3) and MET (3). Other mutations were found in KRAS, NOTCH, APC, and VHL genes. We also detected potential amplifications in the KRAS (4), EGFR (9), PI3KCA (11), AKT (6), FGFR (6), CDKN2A (4) and CDH1(8) genes. Among 43 tumor specimens, 86% of specimens harbored at least one genetic alteration, most of them linked to actionable mutations or amplifications Conclusions: Within HER2 amplified GCs, there are additional subsets with a potentially targetable oncogene. Future testing for these targets will benefit from including HER2 amplified GC patients Supported by the Spanish Ministry of Health, Fondo de Investigaciones Sanitarias grant PI11/01005 and European FEDER (PN I+D+I 2008‐20011).
Survival among metastatic colorectal patients in clinical trials compared to the real world.
Authors: Wang Ziwei , Hwang Lindsay , Murphy James Don 
Published: February 2017

673 Background: Randomized clinical trials play a central role in clinical research though only a small fraction of patients partake in clinical studies. Questions thus arise regarding the generalizability of clinical trial results to the remainder of the population. This study evaluated whether patient survival from randomized clinical trials in metastatic colorectal cancer reflects real world outcomes. Methods: A Pubmed search was used to identify randomized phase III clinical trials of first-line treatment for metastatic colorectal cancer published between 2005 and 2010. We excluded secondary or pooled analyses, second-line treatments, non-metastatic patients, non-English language, and non-randomized studies. Thirty-one clinical trials met these criteria, comprised of 79 distinct clinical trial arms. Overall survival among clinical trial patients was compared to metastatic colorectal cancer patients within the Surveillance, Epidemiology, and End Results (SEER) program. Within SEER, we restricted the analysis time-period and age of patients to match the enrollment period and age of patients within each individual clinical trial. Results: The clinical trials enrolled a total of 16,614 patients. Among all clinical trial arms the median survival ranged from 6.7-62 months, 1-year survival ranged from 30-97%, and 2-year survival ranged from 6-88%. Compared to SEER, the median survival was higher in 95% of the individual clinical trial arms by an average of 5.4 months (p<0.0001). The 1-year survival was higher in 94% of the clinical trial arms by an average of 16.7% (p<0.0001). The 2-year survival was higher in 71% of the clinical trial arms by an average of 7.2% (p<0.0001). Conclusions: This study found substantially improved survival among clinical trial participants compared to patients in the SEER database suggesting that survival estimates from clinical trials may not generalize to the “real world.” Potential patient factors such as differences in underlying comorbidity, performance status, disease burden, as well as variation in treatment could not be addressed in this study, though these factors likely explain some of the observed survival differences.
Surgical management of the primary tumor in stage IV colorectal cancer: A validation study.
Authors: Ahmed Shahid , Pahwa Punam , Kanthan Selliah , Fields Anthony L.A. , Le Duc Minh , Haider Kamal , Reeder Bruce , Ahmed Osama , Alvi Riaz , Iqbal Nayyer , Abbas Tahir , Zaidi Adnan , Arnold Florence , Yadav Sunil , Sami Amer , Leis Anne 
Published: February 2017

675 Background: The observational studies have demonstrated superior survival of patients with stage IV CRC who undergo surgical resection of the primary tumor (SRPT). Yet the results are not confirmed in the setting of a randomized controlled trial. Lack of randomization and failure to control the prognostic variables that affect survival including performance status (PS) are the major critiques to the findings of observational studies. Our group has demonstrated that SRPT improves survival of stage IV CRC patients, who were diagnosed between 1992-2005, independent of age and PS (Cancer. 2014;120:683). The current study is undertaken to validate our findings in patients who are treated with modern chemotherapy. Methods: A cohort of 569 patients with stage IV CRC diagnosed between 2006-2010 in Saskatchewan was evaluated. Cox regression model was used to adjust survival for important prognostic variables. Results: Median age was 69 years (59-95) and M:F was 1.4:1. 35% had ECOG PS of >1. 313 (55%) patients underwent SRPT. Median followup time was 11 months (inter-quartile range 2-26). 57.3% received chemotherapy, 91.4% received FOLFIRI or FOLFOX and 67% received anti-EGFR inhibitors and or bevacizumab. Median overall survival (OS) of patients who had SPRT and received chemotherapy was 27 months compared with 14 months if they did not have surgery (p<0.0001). Median OS of patients who received all active agents and had SPRT was 39 months (95% CI: 25.1-52.9). On multivariate analysis SRPT, hazard ratio (HR) for mortality of 0.44 (95% CI: 0.35-0.56), use of chemotherapy, HR 0.33 (95% CI: 0.26-0.43), metastasectomy, HR 0.43 (95% CI: 0.31-0.58), second line therapy, HR 0.50 (95% CI: 0.35-0.70), and third line therapy, HR 0.58 (95% CI: 0.41-0.83) were independently correlated with superior survival. Elevated alkaline phosphatase, (HR 1.50 (95% CI: 1.20-1.78), grade 3 tumor, HR 1.33 (95% CI: 1.10-1.62), leukocytosis, HR 1.32 (95% CI: 1.05-1.66), stage IVb disease, HR 1.31 (95% CI: 1.10-1.56), and ECOG PS>1, HR 1.30 (95% CI: 1.04-1.57) were correlated with inferior survival. Conclusions: Our study supports SRPT in patients with stage IV CRC who are treated with modern combination of chemotherapy and biologics.
Contact x-ray brachytherapy 50 kV (CXB) for organ preservation in T2 T3a-b rectal cancer: Lyon-Nice experience in 120 patients.
Authors: Doyen Jerome , Francois Eric , Frin Anne-Claire , Benezery Karen , Zhou Fuxiang , Romestaing Pascale , Chapet Olivier , Barbet Nicolas N. , Gerard Jean-Pierre 
Published: February 2017

676 Background: Organ preservation (avoiding TME surgery) for T2 T3 a-b rectal cancer is a field of active clinical research. Contact X Ray CXB combined with external beam radiotherapy (EBRT) ± concurrent chemotherapy (CRT) is an attractive method to achieve clinical complete response (cCR) and consequently rectal preservation. We report an overview of 120 patients treated with CXB+EBRT over a 25 year period in Lyon since 1986 and then in Nice until 2012. Methods: Between 1986 and 2012, 120 patients presenting rectal adenocarcinoma T2 T3a-b (distal rectum: 87; middle rectum: 33) were treated with CXB +EBRT with conservative intent. In Lyon (1986-2001), 80 patients median age: 73y; T2:52; T3:28) risk were treated using CXB (80-110 Gy/3-4 fr/4-6 weeks) followed by EBRT (39 Gy/13 fr/18 days) and 192 Iridium implant boost (20 Gy). When cCR was achieved, close surveillance was proposed. In Nice (2002-2012), 40 patients (median age 81y; T2:22; T3:18) received CXB same regimen as in Lyon (using new Papillon 50 machine since 2009) + EBRT (45-50 Gy/5weeks) with concurrent chemotherapy (5-FU or Capecitabine). When cCR was achieved close surveillance was proposed or local excision (13 pts). Results: Median follow-up time 58 months in both groups. Local relapse occurred mainly in the 2 first years. Isolated lymph node recurrence <5%. Bowel function good or excellent when rectum preserved. Main clinical outcomes in table (some improved results in Nice possibly due to better treatment approach and patient selection). Conclusions: CXB with EBRT and concurrent capecitabine achieve safely high rate of cCR with organ preservation. The OPERA randomized trial will reproduce Lyon R 96 trial (Gerard JP, JCO 2004;22:2404) and test the superiority of CXB boost for organ preservation. [Table: see text]
Establishment and characterization of patient-derived tumor xenograft using gastroscopic biopsies in gastric cancer.
Authors: Shen Lin , Gao Jing , Zhu Yan , Tian Tiantian , Li Yan Yan , Li Na , Zou Jianling 
Published: February 2017

68 Background: The patient-derived tumor xenograft (PDTX) model has become the most realistic model for preclinical studies. PDTX models of gastric cancer using surgical tissues are reported occasionally; however, the PDTX model using gastroscopic biopsy, which is presented in this study, is very rare. Methods: A total of 185 fresh gastroscopic biopsies of gastric cancer were subcutaneously transplanted into NOD/SCID (Nonobese Diabetic/Severe Combined Immunodeficiency) mice. The characteristics of PDTX were identified by hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), dual-color in-situ hybridization (DISH), and targeted next-generation sequencing. Chemosensitivity of PDTX model was tested using chemotherapy regimens based on patients. Results: Sixty-three PDTX models were successfully established (34.1%, 63/185) and passaged to maintain tumors in vivo, and the mean latency period of xenografts was 65.86±32.84 days (11-160 days). Biopsies of prior chemotherapy had a higher transplantation rate (52.1%, 37/71) than biopsies after chemotherapy (21.9%, 25/114; P<0.01). No differences were found between the latency period of xenografts and characteristics of patients. The pathological and molecular features of PDTX as well as chemosensitivity were highly consistent with those of primary tumors of patients. The genetic characteristics were stable during passaging of PDTX models. Conclusions: PDTX models using gastroscopic biopsies in gastric cancer were demonstrated for the first time, and the biological characteristics of the PDTX models were highly consistent with patients, which provided the best preclinical study platform for gastric cancer. [Table: see text]
Patterns of colorectal cancer care in the United States: 1990-2010.
Authors: Murphy Caitlin C. , Harlan Linda C , Lund Jennifer Leigh , Lynch Charles , Geiger Ann M. 
Published: February 2017

684 Background: Colorectal cancer (CRC) incidence and mortality have declined in the U.S. over the past two decades. Much of the decline can be attributed to screening and advances in treatment. Few studies have evaluated the extent to which recommended therapies have been adopted in community settings and temporal changes in patterns of care. Methods: Patients diagnosed with stages II and III CRC were randomly sampled from the population-based Surveillance, Epidemiology, and End Results (SEER) program in 1990-91, 1995, 2000, 2005, and 2010 (n=7,056). Treatment data were obtained through medical record review and physician verification. We described the receipt of adjuvant chemotherapy among colon cancer patients and preoperative or postoperative radiation therapy among rectal cancer patients. Log-binomial regression was used to examine factors associated with receipt of therapy. Results: Receipt of adjuvant chemotherapy increased among stages II and III colon cancer patients from 1990 (stage II: 22%, stage III: 55%) to 2005 (stage II: 32%, stage III: 72%) and decreased in 2010 (stage II: 29%, stage III: 65%). Chemotherapy regimens changed over time; there was an increase in the use of capecitabine (3% in 2000 to 24% in 2010) and oxaliplatin (6% in 2000 to 79% in 2010). Stage III colon cancer patients who were older (75-79 years: RR 0.82, 95% CI 0.72, 0.94; ≥80 years: RR 0.36, 95% CI 0.27, 0.49) or had a comorbidity score ≥ 2 (RR 0.54, 95% CI 0.34, 0.86) were less likely to receive adjuvant chemotherapy. Receipt of radiation therapy among stages II and III rectal cancer patients increased across all study years from 46% to 66%, with a shift toward preoperative therapy in 2005. From 2005 to 2010, receipt of neoadjuvant chemoradiation followed by surgery and postoperative chemotherapy nearly doubled (11% in 2005 to 21% in 2010). Increasing age (75-79 years: RR 0.60, 95% CI 0.48, 0.75; ≥80 years: RR 0.34, 95% CI 0.25, 0.45) was associated with lower chemoradiation use in rectal cancer. Conclusions: Our findings demonstrate increased adoption of adjuvant therapies for both colon and rectal cancer patients and differences in therapy receipt by age, comorbidity, and diagnosis year. Improved receipt of adjuvant therapies in the community may further reduce CRC mortality.
Exceptional responses in patients with metastatic colorectal cancer enrolled in first-in-man studies from 2002 through 2012.
Authors: Patel Shiven B. , Tometich Danielle , Reese Zachary L , Sharma Sunil , Garrido-Laguna Ignacio 
Published: February 2017

687 Background: Understanding exceptional responses to therapy at the molecular level may open new venues for the treatment of patients with metastatic colorectal cancer (mCRC). Responses in first-in-man (FIM) studies with targeted therapies are rare and may indicate that actionable genetic aberrations are present in these patients. Methods: We utilized Scopus using the search term “phase 1 and solid tumors” to collect all FIM studies published between 2002 and 2012. We identified patients with mCRC who attained an exceptional response to therapy defined as a complete response (CR) or a partial response (PR) lasting > 6 months (m). Results: We identified 118 FIM studies enrolling 5,369 patients with advanced malignancies. mCRC was the most common tumor type, totaling 1,055 (19.6%) patients. Of these, two patients enrolled in protocols with MDX-1106 (anti PD-1) and RG7180 (mAb EGFR) attained a complete response (CR). Five patients had PR lasting > 6 m. These patients were treated with RG7180 (time on study 7.8 m), Apatinib, a VEGFR tyrosine kinase inhibitor (8.5 and 7.1 m), PV701, a replication-competent oncolytic virus (10 m) and RO4929097, a gamma-secretase inhibitor (7 m). In addition two patients had PR lasting < 6 m with regorafenib (5.3 m) and RG7180 (5.6 m). This database of exceptional responders to therapy will be publicly available at Huntsman Cancer Institute website. Currently, regorafenib and EGFR mAbs (cetuximab and panitumumab) are approved for use in mCRC. EGFR mAbs have shown improvement in survival in RAS wild-type mCRC. Clinical trials are underway evaluating apatinib. Anti-PD1s have shown limited activity as single agents in mCRC and are currently undergoing testing in combination with chemotherapy. Conclusions: We identified exceptional responses among patients with mCRC enrolled in FIM in the last decade. Ongoing efforts are directed to conduct next generation sequencing (NGS) in archived tissue from these patients. Ultimately, this initiative may facilitate the identification of biomarkers of response to be tested in clinical trials with these or novel drugs sharing similar mechanisms of action.
Patient's self-reported adherence to capecitabine on XELOX as adjuvant therapy for colorectal cancer.
Authors: Kawakami Kazuyoshi , Yokokawa Takashi , Sugita Kazuo , Hagino Akane , Suzuki Kenichi , Oniyama Sayaka , Kohdo Satoshi , Machida Yohiaki , Suenaga Mitsukuni , Mizunuma Nobuyuki , Yamaguchi Tohiharu , Hama Toshihiro 
Published: February 2017

690 Background: Capecitabine plus oxaliplatin (XELOX) has been established as adjuvant therapy for stage II/III colon cancer. Adherence to capecitabine is particularly important with XELOX to maintain appropriate curative effect. In this study, we monitored the adherence to capecitabine during adjuvant treatment with XELOX, and investigated the candidate factors that might decrease the adherence. Methods: The study included 139 consecutive patients who received XELOX treatment as adjuvant therapy for colorectal cancer between November 2011 and March 2014. Adherence to capecitabine was checked by pharmacists using a patient-reported treatment diary at a pharmaceutical outpatient clinic. Adherence rate was defined as the number of which a patient took capecitabine between d1 evening and d15 morning per 28 in each treatment cycle. The relative dose intensities and the deteriorating factors of adherence to capecitabine were retrospectively surveyed from electronic patient records. Results: 70 male and 69 female patients received adjuvant XELOX. Median adherence rate was 95.4% (n=139) in the first cycle of XELOX treatment, which gradually rose to 98.3% (n=121) in the eighth cycle. The median relative dose intensity of capecitabine was 76.7%. The main factors contributing to decreased adherence to capecitabine were diarrhea (34.7%) and nausea/vomiting (20.2%), peripheral neuropathy (10.7%). Conclusions: In this study, patient-reported adherence to capecitabine on XELOX treatment in clinical practice was highly maintained during all treatment cycles, and poor-adherence appeared to correlate with gastrointestinal events such as diarrhea, nausea, or vomiting. Our results suggest that assessment for compliance along with management of adverse events is needed to maintain treatment effect in clinical practice.