bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic impact of baseline CEA level and surgery of primary tumor among patients with stage IV denovo colon cancer.
Authors: Dawood S. S. , Gonzalez-Angulo A. M. , Eng C. 
Published: February 2017

503 Background: Surgical resection of primary tumor among pts with stageIV denovo colorectal cancer is controversial. Prognostic role of baseline CEA level in the same cohort has yet to be defined. The objective of this study was to determine the prognostic value of CEA and surgical resection of primary tumor among pts with stage IV denovo colorectal cancer in the era of biologic therapy and to determine subgroups with improved survival outcome. Methods: The Surveillance, Epidemiology and End Results Registry was searched to identify patients with stage IV denovo colorectal cancer diagnosed between 2004-2007. Colorectal cancer specific survival (CCS) was estimated using the Kaplan-Meier product limit method. Cox models were fitted to assess the multivariable relationship of various pt and tumor characteristics and CCS. Results: 19,437 pts were identified with stage IV denovo colorectal cancer. Median CCS was 15M. Median CCS among pts with primary tumor removed was 20M vs 8M (primary intact; p<0.001). Median CCS among pts who had elevated vs. non elevated CEA was 14M vs 23M (p<0.0001). Among pts who had primary tumor surgery median CCS among pts who had elevated vs. non elevated CEA was 19M vs 29M (p<0.0001). Among pts who had primary tumor and distant disease surgically removed, the median CCS among pts who had elevated vs. non elevated CEA was 24M vs 35M (p<0.0001). By multivariable analysis, pts with elevated CEA had a 51% increased risk of death from colorectal cancer compared to those with a non elevated CEA level (HR=1.51, 95%CI 1.40-1.65, p<0.0001). Pts who underwent primary tumor surgery had a 33% decreased risk of death from colorectal cancer compared to those who did not (HR=0.67, 95%CI 0.58-0.78, p<0.0001). Other factors significantly associated with a decreased risk of death from colorectal cancer included low grade disease, non visceral metastases, surgical resection of metastases, younger age and white race. Conclusions: In this large population study, elevated baseline CEA level and surgical resection of the primary tumor had a significant impact on survival outcomes. The best prognostic group were those pts with normal baseline CEA level who proceeded to surgical resection for their primary tumor. No significant financial relationships to disclose.
Oncologic outcomes following radical resection with intraoperative electron radiation therapy in patients with recurrent colorectal cancer.
Authors: Llaguna O. H. , Meyers M. O. , Smith M. B. , Stitzenberg K. B. , Deal A. M. , O'Neil B. H. , Bernard S. A. , Wang A. Z. , Tepper J. E. , Calvo B. F. 
Published: February 2017

508 Background: Of the 40,000 rectal cancer patients treated annually, up to 15% will experience a local recurrence (LR). Resection only series for LR report 30–60% positive margin rates. For this reason our institution utilizes intra-operative electron radiation therapy (IOERT) in patients undergoing resection of locally advanced rectal cancer recurrences (LA-RRC). The purpose of this study was to evaluate the oncologic outcomes of patients treated for a LA-RRC with resection and IOERT Methods: Under IRB approval a prospective database of patients with LA-RRC undergoing resection and IOERT from April 2001 to January 2010 was analyzed. Demographic, clinical, and pathologic variables were collected. The Kaplan-Meier method estimated 5-year overall survival (OS) and Fisher's Exact test's explored associations for developing a LR. Results: Fifty patients (32 male, mean age 58 ± 11) underwent resection and IOERT (median dose 1500 cGy, energy 9 MeV). Primary procedures included pelvic exenteration (n = 17), APR (n = 10), LAR (n = 7), isolated pelvic/retroperitoneal tumor (n = 7), para-aortic lymphadenectomy (n = 7), and partial colectomy (n = 2). 56% (n = 28) required multi-visceral resections including partial/total cystectomy (n = 14), small bowel resection (n = 10), vaginectomy (n = 6), hysterectomy (n = 3), oophorectomy (n = 3), nephrectomy (n = 2), and other (n = 4). 34 pelvic sidewall resections and 12 partial sacrectomies were required. Margins were R0 in 37 (74%) and R1 in 13 (26%). Median LOS was 10 days and there were no peri-operative deaths. Five-year OS was 32% with a 19-month follow-up of survivors. 32% (n = 16) developed a pelvic LR, of which 2 were isolated and 14 were in the setting of distant metastasis. No difference was noted in OS (p = 0.5) or LR (p = 0.3) in patients with R0 vs. R1 resections. Initial T (p = 0.1), N (p = 0.2), and stage (p = 0.7) were not found to be associated with LR. Conclusions: This study reveals that resection combined with IOERT provides good local control and reasonable long-term survival in patients with LA-RRC. The similar OS and LR following an R0 and R1 resections could be interpreted as a measure of the beneficial effect of IOERT on microscopic disease. No significant financial relationships to disclose.
Phase II study of preoperative bevacizumab, capecitabine, and radiotherapy for resectable locally advanced rectal cancer.
Authors: Martinez Villacampa M. , Santos C. , García M. , Navarro V. , Teule A. , Losa F. , Pisa A. , Lema L. , Biondo S. , Salazar R. 
Published: February 2017

516 Background: Bevacizumab into chemoradiotherapy appears safe and active in locally advanced rectal cancer (LARC).This study evaluates whether the addition of bevacizumab to capecitabine-based chemoradiotherapy in the preoperative treatment of LARC improves pathological complete response rate (pCR). Methods: Open-label, unicentric, phase II study in patients with resectable LARC (stage II or III), with or without nodal involvement and no evidence of distant metastases. Treatment schedule of 4-cycles: bevacizumab administered iv on day 1 (10 mg/kg in the first cycle and 5 mg/kg in the following 3 cycles) and capecitabine (900mg/m2/bid) in the 2nd cycle (5 d/wk) concomitantly with radiotherapy 45Gy (25 fractions of 1.8Gy/day) over 5 weeks. Surgical resection was scheduled 6-8 weeks after therapy completion. Preliminary results from ITT analysis are presented. Results: Of the 43 patients included, 41 comprised ITT population. Baseline characteristics: median age 63 (55-67) years; male 76%; ECOG 0/1 49%/51%; stage T3/N1 80.5%/58.5%; nodal metastases 85%. 39 patients underwent surgery, 9 abdominoperineal and 30 anterior resection. No evidence of metastasis after surgery in 97%. Total mesorectal excision was performed in 69% of patients and 85% underwent R0 resection. Sphincter-preservation was achieved in 79.5%. Downstaging occurred in 82%. Among 39 patients evaluable for pathological response, 7.7% experienced pCR, 69.2% partial response and 20.5% stable disease. Grade 3/4 toxicities: 9.8% lymphopenia (all related to capecitabine and 4.9% to bevacizumab), 2.4% neutropenia (capecitabine-related), 2.4% radiodermatitis (related to RT and capecitabine) and 2.4% vasospastic angina (bevacizumab and capecitabine-related). 13 patients had postoperative complications not treatment-related. The most common were wound infection (6), intra-abdominal collection (3), wound dehiscence (2) and paralytic ileus (2). Conclusions: Preoperative regimen with bevacizumab, capecitabine and RT is active for LARC with promising results of R0 resection, sphincter- preservation and tumour downstaging as well as manageable toxicity. Further studies are ongoing to confirm these data. No significant financial relationships to disclose.
Phase I study of everolimus (RAD001) with irinotecan (Iri) and cetuximab (C) in second-line metastatic colorectal cancer: Hoosier Oncology Group GI05-102.
Authors: Myre B. , Yu M. , Picus J. , Bufill J. A. , Harb W. A. , Burns M. , Spittler A. J. , Zeng Y. , Currie C. R. , Chiorean E. G. 
Published: February 2017

523 Background: Preclinically, mTOR and EGFR inhibitors are synergistic. We hypothesize that the mTOR inhibitor RAD001 would enhance efficacy and prevent resistance when added to an anti-EGFR agent. The purpose of the phase I portion of this study was to determine the safety and maximum tolerated dose (MTD) of daily RAD001 combined with weekly Iri and C in mCRC. Methods: Pts who failed first-line therapy, including an Iri-regimen, were treated with Iri 125 mg/m2 weekly x 2 every 3 weeks, C 400 mg/m2 loading dose, then 250 mg/m2 weekly, and escalating doses of RAD001 orally: 5 mg qod, 5 mg qd and 10 mg qd during 21-day cycles, with a “3+3” design. The study was amended after the first 9 pts enrolled, to include stopping rules for excessive toxicity beyond what was expected for diarrhea, nausea/vomiting and febrile neutropenia due to Iri, and skin rash due to C. Enrollment excluded pts with UGT1A1*28, but allowed KRAS mutated mCRC. RAD001 PK was done on C2D1, and archival tumors were analyzed for pharmacodynamic markers. Results: 28 pts were enrolled, median age 61 y (25-77), 15 male, ECOG PS 0/1 (19/9). Reasons for treatment discontinuation were: PD (7), adverse events (AEs) (6), pt withdrawal, symptomatic deterioration and non-compliance (1 each). Prior to study's amendment* (n=9), 3 pts were not evaluable for DLT due to: Iri intolerance after one dose (1), non-compliance (1) and gr 3 C infusion reaction (1). DLTs and number of cycles are listed in Table. Following protocol amendment, 2 pts had DLT in cohort 3 (gr 3 mucositis), thus the MTD was 5 mg RAD001. The most common grade 3/4 AEs were: diarrhea (10), neutropenia (5), fatigue (4), acne-rash (4), mucositis (2), nausea (2), vomiting (1). Among 19 pts evaluable for response, there were 1 CR, 2 PR, (RR 16%), 9 SD (47%), 7 PD (37%). PK and pharmacodynamic data is ongoing. Conclusions: The MTD of RAD001 of 5 mg QD with Iri/C weekly is safe and clinically active. A randomized phase II study is near starting accrual. [Table: see text] [Table: see text]
Retroperitoneal dissemination of colorectal ovarian metastases: Basis for rationale use of lymphadenectomy.
Authors: Eveno C. , Goárá D. , Tzanis D. , Dartigues P. , Dumont F. , Benhaim L. , Ducreux M. , Elias D. 
Published: February 2017

535 Background: Retroperitoneal lymph nodes are a common site of metastases in primary ovarian cancers and primary peritoneal carcinoma, therefore pelvic and paraaortic lymphadenectomy are recommended. Colorectal ovarian metastases are mostly associated to peritoneal carcionomatosis (PC), which treatment is based on complete cytoreductive surgery (CCRS) associated to intraperitoneal chemotherapy (IPC). The aim of this study was to compare the rate of nodal (pelvic, paraaortic) recurrences, between 2 groups of patients (pts) operated on PC with ovarian metastases (OM) or without OM. Methods: From January 1994 to December 2009, all consecutive women who underwent CCRS plus IPC, were selected from a prospective database. Demographics, tumor characteristics, surgical procedures and chemotherapy, were analyzed and compared. Results: One hundred and five pts were identified; 63 (60%) had ovarian metastasis (synchronous or metachronous). Groups were comparable for all variables, except for the median peritoneal cancer index which was lower in the OM group (9 vs.10.5, p<.05). Nodal recurrences were diagnosed in 19 pts (18%), in paraaortic nodes in 14 pts (74%), pelvic nodes in 7 pts (36%), both in 2 pts (10%) and were associated to other relapse in 15 pts (80%). All these nodal recurrences occurred in the OM group (30% vs. 0, p<.001). After a median follow-up of 74 months (10-196), 3-year overall survival rate was greater in pts without nodal recurrences (71 vs 41 %, p=0.37) and at the end of the study, there was significantly more patients died of disease in case of nodal recurrence (24/44 vs 5/19, p=.04). Conclusions: Nearly one third of patients with ovarian metastases experienced paraaortic and pelvic nodes recurrences. This may due to the specific pattern of lymphatic spread of ovary, well known in primary carcinomas. Therefore, systematic lymphadenectomy should be studied in patients with colorectal ovarian metastases treated in curative intent. No significant financial relationships to disclose.
Phase Ib study of drozitumab combined with first-line FOLFOX plus bevacizumab (BV) in patients (pts) with metastatic colorectal cancer (mCRC).
Authors: Rocha Lima C. S. , Baranda J. C. , Wallmark J. , Choi Y. , Royer-Joo S. , Portera C. C. 
Published: February 2017

546 Background: Drozitumab is a monoclonal antibody that triggers tumor cell apoptosis by selective agonistic interaction with the Apo2 ligand/TNF-related apoptosis-inducing ligand death receptor 5. This study assessed the safety of drozitumab combined with FOLFOX+BV as first-line therapy in mCRC pts. Methods: Multicenter, open-label study of 2 sequential dose cohorts. Cohort 1 = 3.5mg/kg after 5 mg/kg loading dose (n=3); Cohort 2 = 7mg/kg after 10mg/kg loading dose (n=6). Pts were treated on 14-day cycles (drozitumab, FOLFOX, and BV 5mg/kg on Day 1 of cycle) until disease progression or toxicity. Dose-limiting toxicity (DLT; primary outcome measure) was assessed through 2 cycles (Days 1-28). Adverse events (AE) were recorded through all cycles. Response was assessed by RECIST. Results: A total of 9 pts received 1-22 cycles (median 11) of drozitumab. No DLTs occurred. Most frequent AEs were neutropenia (89%), diarrhea (78%), nausea (78%), fatigue (67%), and anemia (56%). Most frequent Grade ≥3 AEs were fatigue (33%), anemia (22%), diarrhea (22%), hypokalemia (22%), and neutropenia (22%). One pt was discontinued from study drug due to serious AE of vancomycin-resistant enterococcal sepsis assessed as unrelated to drozitumab. Other reasons for discontinuation included disease progression (4 pts), physician's decision (3 pts) and patient's decision (1 pt). Among the 9 patients, best responses included five Partial Responses (2 confirmed and 3 unconfirmed), three Stable Disease, and one missing. The sponsor stopped the study enrollment early for reasons unrelated to safety or efficacy. Conclusions: Addition of drozitumab to first-line FOLFOX+BV was well tolerated overall in these mCRC pts. AEs were similar to those previously reported for FOLFOX+BV alone. Tumor responses suggest no adverse interactions between drozitumab and the chemotherapy evaluated in this study. [Table: see text]
A randomized, double-blind, placebo-controlled trial for prevention of oxaliplatin-induced neuropathy symptoms with pregabalin.
Authors: Karthaus M. , Karapetis C. S. , Brown M. , Pavlakis N. , Trarbach T. , Marschner N. , Duerk H. A. , Manzione L. ,   Pregabalin Study Group
Published: February 2017

553 Background: Sensorial peripheral neuropathy (PNP) is a major limitation for pts receiving oxaliplatin-based ctx for CRC. Pregabalin is widely used for treatment of oxaliplatin-induced PNP. We evaluated the efficacy of pregabalin vs. placebo for the prevention of paresthesia from the onset of oxaliplatin-based ctx over each cycle. Methods: Rd, db, placebo-controlled study in adult CRC pts with ECOG 0-2 to undergo a new oxaliplatin/5-FU/FA-based ctx. Pts were excluded if they had neuropathic pain or other of painful paresthesia prior to baseline. Paresthesia, dysesthesia, and pain were rated on a numerical scale (NRS 0-10) every day. Primary endpoint was the time of onset of persistent symptoms (NRS >4). Results: Of the 69 screened pts, 64 were randomized and 61 received study medication (32 pregabalin vs. 29 placebo). Pts were balanced in both arms regarding age, sex, stage, and ctx. There were no differences between both treatment groups for all PNP parameters at any cycle. One pt in both arms developed paresthesia (5.3%) after 9 cycles of ctx, 1 pt had persistent pain (placebo arm). During the follow-up period persistent paresthesic, dysesthesic, and persistent pain developed in 2 vs. 1, 2 vs. 2, and 0 vs. 2 pts, respectively. The study was terminated after a blinded data review found that there were very few events of persistent symptoms, which was then confirmed an interim analysis. Nausea and anorexia were the most frequently reported AE in both groups. Conclusions: The results of this study, which was terminated early at interim analysis, is that too few patients developed persistent symptoms to allow any meaningful treatment difference for prevention of neuropathic pain related to oxaliplatin by pregabalin. There remains an unmet need for oxaliplatin-induced PNP with new trial design issues in this field urgently needed. No significant financial relationships to disclose.
Primary non-Hodgkin lymphoma of the colon among patients in the Veterans Affairs Health System.
Authors: Tashi T. , Thota R. , Krishnamurthy J. , Sama A. R. , Aldoss I. T. , Gonsalves W. , Ganti A. , Townley P. , Silberstein P. T. , Subbiah S. 
Published: February 2017

554 Background: Primary non-Hodgkin lymphoma (NHL) of the colon is rare. There are no randomized controlled trials describing treatment outcomes for this tumor. We provide the largest descriptive study of this tumor to date. Methods: Retrospective analysis of 109 patients diagnosed with primary non-Hodgkin lymphoma of the colon from 1995 to 2008 was done via the Veteran's Affairs Central Cancer Registry. By definition, all cases presented with a lymphomatous involvement of the colon as the first manifestation of their disease with no previous diagnosis of NHL of any type or site. Demographic, staging, histology, treatment, and outcome data was recorded. Lymphomas were classified as aggressive versus indolent based on their histology. Results: There were 36,260 colon cancers diagnosed in 1995-2008 of which 109 (0.3%) were primary non-Hodgkin colon lymphomas. The median age of diagnosis was 67 years. 55 pts had aggressive disease, 27 pts had indolent disease, and 27 pts had inadequate histological data. Diffuse large B cell lymphoma (73%) was the most common aggressive lymphoma whereas it was marginal zone (56%) in the indolent group. The indolent group had 5- year survival rate of 76.9% compared to 48.6% for the aggressive group. Both groups had received different treatment regimens as seen in the Table with variable mean survival outcomes. Conclusions: Our data suggests addition of postoperative adjuvant chemotherapy appears superior to surgery alone in the treatment of aggressive disease whereas it does not appear to provide any benefit in the treatment of indolent disease. However, patient numbers are too small to draw definite conclusions and warrant future investigation in multinational randomized fashion. [Table: see text] No significant financial relationships to disclose.
Effectiveness and safety in very elderly patients treated by bevacizumab (BV) plus chemotherapy in first-line therapy of metastatic colorectal cancer: Results of ETNA, a French cohort study.
Authors: Smith D. , Rouyer M. , Noize P. , Lassalle R. , Bernard O. , Burki F. , Guichard P. , Ravaud A. , Moore N. , Fourrier-Ráglat A. ,   ETNA Study Group
Published: February 2017

555 Background: In view of the ageing population, oncogeriatrics has become a priority for public health. Elderly cancer patients are often excluded from clinical trials and there is no therapeutic standard for their care management. Cohort studies have been conducted in US and Europe but not in France. The ETNA study aimed to describe BV use and survival outcomes in real-life practice. Here, the population aged >75 years was compared to that aged >75. Methods: ETNA is a cohort study conducted in 28 French centers that included 411 patients initiating BV between Jan 2006 and Dec 2007, with 24 month follow-up. Results: Fifty-one patients (12.4%) of the cohort were over 75 years old: mean age 78.3 years (vs 61.9 years for the rest of the cohort), male 66.7% (vs 56.1%), ECOG≥2 17.6% (vs 10.8%). BV was combined with FOLFIRI/XELIRI in 88.2% of patients aged >75 years (vs 87.5%) and FOLFOX/XELOX in 11.8% (vs 12.2%). Median duration of BV treatment was 5.6 months (m) (vs 5.5 m), and median duration of the 1st-line was 10.3 m (vs 9.8 m). More patients >75 years had treatment-free intervals (39.2% vs 28.6%), and 13.7% had a maintenance therapy (vs 12.8%). Curative surgery performed in 15.7% of patients (vs. 20.6%). Among the 43 patients who discontinued the 1st-line, only 9.3% discontinued BV prematurely (vs 18.2%). The incidence of any grade-3/4 adverse event was 43.1% (vs 41.7%). In-line with the known safety profile of BV (any grade), hypertension was observed in 21.6% (vs 18.9%), proteinuria 23.5% (vs 27.2%), there were no GI perforations (vs 0.3%), thrombotic events 5.9% (vs 7.8%), and grade 3/4 arterial thrombotic events 2.0% (vs 0.6%). The 1-year OS rate was 78.0%, 95%CI [63.9-87.2] (vs 80.5%, 95%CI [76.0-84.2]) and the median OS was not reached for both groups. The median PFS was 10.6 m, 95%CI [9.0-12.8] (vs 9.9 m, 95%CI [9.3-11.1]). Conclusions: Effectiveness and safety of BV plus chemotherapy in elderly patients were similar to those of the rest of the ETNA cohort. Estimations of survival outcomes (1-year OS rate, median OS and PFS) were also comparable to those found in elderly patients (75-80 years) from the BRITE cohort (72.0%, 20.3 m and 10.0 m, respectively). No significant financial relationships to disclose.
Are there differences in chemotherapy (CT) administration and outcomes in elderly patients (pts) diagnosed with colorectal cancer (CRC)?
Authors: Sehgal R. , Krug C. E. , Reifer J. , Tria Tirona M. , Douglas W. G. , Edwards P. , Gress T. W. 
Published: February 2017

557 Background: CRC is the third most common cancer in men and women in the United States. The median age at diagnosis is 70 years (yrs). Controversy exists in the literature regarding benefit from CT in elderly pts with CRC. We performed a retrospective study to evaluate CT rate and its benefit in different age groups of pts with CRC. Methods: Data on pts diagnosed with CRC from 1993-2008 were collected from the Cancer Information Resource File. Complete data on age, gender, stage, tumor characteristics, treatment, and overall survival (OS) were available on 32,177 pts and were analyzed by age in four categories: < 50, 50-69, 70-79, and ≥ 80 yrs. Results: Of 32,177 pts, 7% were < 50, 35% were 50-69, 32% were 70-78, and 26% were ≥ 80 yrs. The table reports pt demographics, median OS (MOS) by age and stage, and rates of CT by age and stage. As reported in the table, use of CT declined with advancing age, regardless of stage. Multivariate Cox regression analysis simultaneously adjusted for age at diagnosis, gender, race, stage, and grade revealed that CT was associated with reduced mortality in all age categories: < 50 yrs, HR 0.75; 50-69, HR 0.61; 70-79, HR 0.53; and ≥ 80, HR 0.55 (all p < 0.01). Conclusions: Older pts receive CT less frequently than younger pts. The use of CT in the elderly was associated with a reduced mortality, similar to that seen in younger pts. Younger pts were more likely to present with stage IV disease when compared to the elderly. Randomized, prospective trials are required to explore the differences noted. [Table: see text] No significant financial relationships to disclose.