bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of sarcopenia on survival in locally advanced rectal cancer.
Authors: Gamenthaler Andrew , Siegel Erin M. , Clark Whalen , Chen Ann , Zhao Xiuhua , Maddox Kristen , Shibata David 
Published: February 2017

604 Background: The association between sarcopenia (or muscle loss) and worse oncologic outcomes has been documented in several different cancers and is thought to be a potential marker of a diminished host response to tumor. The prognostic role of sarcopenia in rectal cancer (RC) patients has yet to be elucidated. We sought to examine the impact of radiologically-defined sarcopenia on outcomes of RC patients treated by neoadjuvant chemoradiation (NCR) and radical resection. Methods: Between 1998-2010, we identified 90 patients with stage II/III RC treated by NCR and radical surgery. Sarcopenia was assessed using 3 CT-based measures derived at the L4-L5 level including mean psoas density (MPD; Hounsfield Units), total psoas area (TPA; mm2) and muscle mass index (MMI=TPA/height2; mm2/m2). Clinicopathologic data (age, gender, pretreatment and final tumor stage, treatment response and CEA level) were collected. Associations were analyzed by Wilcoxon Rank Sum while the Kaplan–Meier method, log-rank test, and Cox proportional hazards models were used to evaluate overall survival (OS) and disease-free survival (DFS). Results: Our population consisted of 50 males and 40 females with a median age at diagnosis of 61 (range 35-87). By univariate analyses, only age >61 was associated with the presence of sarcopenia by all 3 measures [MPD (p=0.0003), MMI (p=0.0001), and TPA (p=0.0008)]. Female gender was associated with increased muscle loss by MMI (p<0.0001) and TPA (p<0.0001). By Cox multivariate analysis, MPD (range 14.5-77.3 HU) was independently associated with a worse OS (AHR= 0.94; 95% CI, 0.88-0.99; p= 0.04) and marginally associated with DFS (AHR= 0.95; 95% CI, 0.89-1.00; p= 0.056) when controlling for age, gender and pathologic response. This translates to a 28.5% reduction in risk of death with every 5 HU decrease in MPD. Conclusions: We have demonstrated that pre-treatment sarcopenia as measured by MPD is associated with worse OS and possibly DFS in patients with RC treated by NCR and radical surgery. Larger scale studies of sarcopenia and RC are warranted. Strategies targeting reversal of processes associated with muscle loss may play a potential future role in the multidisciplinary management of rectal cancer.
Positron emission tomography/computed tomography for early treatment response evaluation in metastatic colon cancer.
Authors: Engelmann Bodil E. , Loft Annika , Kjær Andreas , Nielsen Hans J. , von Benzon Eric , Brünner Nils , Christensen Ib Jarle , Gerds Thomas A. , Hansson Susanne H. , Hollander Niels Henrik , Kristensen Michael Holmsgaard , Löfgren Johan , Markova Elena , Sloth Carsten , Højgaard Liselotte 
Published: February 2017

614 Background: Treatment options for metastatic colon cancer (mCC) are widening. We prospectively evaluated serial 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography/ computed tomography (PET/CT) and measurements of tissue inhibitor of metalloproteinases type 1 (TIMP-1), carcinoembryonic antigen (CEA) and urokinase plasminogen activator receptor domain I [uPAR(I)] for early assessment of treatment response in mCC patients. Methods: Thirty-three mCC patients scheduled for first line chemotherapy with capecitabine, oxaliplatin (CAPOX) and bevacizumab participated; 27 were evaluated by PET/CT before treatment, after one and four treatment series. Morphological and metabolic response was independently assessed according to Response Evaluation Criteria In Solid Tumours (RECIST1.1) and EORTC PET criteria. Plasma TIMP-1, plasma uPAR(I) and serum CEA were determined. Results: Metabolic response after one treatment course predicted the ability of CAPOX and bevacizumab to induce morphological response after four treatment series with a sensitivity of 80 %, specificity of 69 % and an Odds Ratio of 13.9 [CI 1.9; 182]. Early metabolically stable or progressive disease was associated with shorter progression-free survival (PFS) (hazard ratio (HR) = 3.2 [CI 1.3; 7.8]). Biomarker levels at early evaluation were associated to shorter PFS (TIMP-1 per unit increase on a log-2 transformed ng/mL scale: HR = 2.23 [CI 1.20; 4.14]; uPAR(I) per 25 fmol/mL increase: HR = 1.36 [CI 1.03; 1.79]). Conclusions: This monocentric study demonstrated predictive value of early metabolic PET response and prognostic value of TIMP-1 and uPAR(I) levels in mCC treated with CAPOX and bevacizumab. Results support investigation of PET/CT, TIMP-1 and uPAR(I) guided early treatment adaptation in mCC.
The importance of sequence in rescheduling bevacizumab and chemotherapy administration in the first-line treatment of metastatic colorectal carcinoma (mCRC).
Authors: Chelis Leonidas , Xenidis Nikolaos , Amarantidis Kiriakos , Diamantopoulos Nikolaos , Boutis Anastasios L. , Koukaki Triantafyllia , Michailidis Prodromos , Christakidis Evagelos , Chalvatzis Athanasios , Matthaios Dimitrios , Deftereos Savas , Courcoutsakis Nikos , Prassopoulos Panagiotis , Kakolyris Stylianos 
Published: February 2017

617 Background: One of the proposed mechanisms of action for bevacizumab is by reducing the interstitial fluid pressure (IFP) allowing an increased penetration and uptake of chemotherapy agents in tumors. Clinical and laboratory data suggest that the decrease of IFP occurs after a few days of bevacizumab administration and intratumoral delivery of chemotherapy increase when bevacizumab precedes chemotherapy. We hypothesized that altering the schedule of BEV/FOLFOX regimen would improve the efficacy of the regimen and increase objective response rate. Methods: Patients (pts) with mCRC or locally advanced colorectal cancer, with ECOG PS 0-2 were eligible. The treatment schedule was Bevacizumab 5mg/Kg on day 1, standard FOLFOX-4 regimen on days 8-9 at cycles repeated every 14 days. Prior 5-FU/oxaliplatin adjuvant treatment was allowed. The pts were treated for 6 months or until reaching a plateau of response. Standard RECIST v1.1 response evaluation criteria were used. Primary endpoint of the study was the percentage of objective response rate, PR+CR (ORR), secondary end points were PFS, OS and toxicity. A Simon two step, minimax, statistical design was used: the minimum accepted ORR was 45% (p0) and the estimated ORR was 65% (p1). Results: Thirty (n=30) pts were enrolled. The median age was 69.5 years, the performance status was 0 (40%), 1 (40%), 2 (20%), the median follow up was 20.75 months and the K-RAS status was wild type for 63.5% and mutant for 36.5%. Seven pts (23.3%) had received prior adjuvant chemotherapy. Five pts had convertible metastatic disease. Four CR (13.33%), 18 PR (60%), 7 SD (23.33%), and one PD (3.3%) were observed for a total ORR of 73.3% and disease control rate (CR+PR+SD) of 96.7%. Four out of five (80%) pts with convertible disease achieved a R0 resection. The PFS was 12.8 months and OS has not been reached yet. One patient experienced a grade 4 event (febrile neutropenia). The study met its primary endpoint and therefore is considered positive. Conclusions: Delivering bevacizumab before chemotherapy in the first-line treatment of mCRC represents a very effective and promising schedule which warrants further investigation in randomized clinical trials.
Adjuvant chemotherapy following neoadjuvant chemoradiotherapy and surgery for locally advanced rectal cancer.
Authors: Laws Kirsten Elizabeth Jean , Wilson Christina , McIntosh David , Harrow Stephen 
Published: February 2017

626 Background: Established guidelines exist for indications of adjuvant chemotherapy in colon cancer. However, in patients receiving neoadjuvant chemoradiotherapy for locally advanced rectal cancer, the benefit of adjuvant chemotherapy remains unproven. We evaluated clinical decision making behind adjuvant chemotherapy for locally advanced rectal cancer patients in our institute. Methods: Patients treated with long course chemoradiotherapy between January 2008 and December 2009 were identified. Exclusion criteria were inoperable disease, postoperative, recurrence, or palliative intent. 231 cases were examined retrospectively for the decisions behind giving or withholding adjuvant chemotherapy. Results: 35 (15%) were ineligible for consideration of adjuvant chemotherapy due to disease progression. 38 patients (16.4%) received chemotherapy in the adjuvant setting and 158 patients (68.4%) were potentially eligible for adjuvant chemotherapy, but did not receive it. The majority of clinicians based their decisions on post operative pathology results, and the key factor in decision making was final pathological stage in 65%. Clinicians considered pre-treatment imaging a key factor in only 14% of cases, despite a considerable number of patients being downstaged from a potentially higher initial pre-treatment stage that could have warranted adjuvant treatment. A considerable number of patients (25%) were deemed unfit for adjuvant treatment following neoadjuvant chemoradiotherapy and surgery due to toxicity of combined treatment. Conclusions: This analysis highlights the difficulty in clinical decision making for adjuvant chemotherapy in rectal cancer. The accuracy of pre-treatment staging is difficult to ascertain and its use to justify post operative treatment uncertain. It appears the majority of clinicians in our institute base their decision on post operative pathology. A considerable number of patients were not fit for consideration of adjuvant treatment due to toxicity of previous treatment. Further research is warranted as to the benefits of adjuvant chemotherapy, particularly in a setting where prior treatment already causes significant toxicity.
Phase II trial of combined chemotherapy with S-1, oral leucovorin, and bevacizumab in heavily pretreated patients with metastatic colorectal cancer.
Authors: Yamaguchi Kazuhisa , Taniguchi Hiroya , Komori Azusa , Narita Yukiya , Uegaki Shiori , Nitta Sohei , Nomura Motoo , Kadowaki Shigenori , Takahari Daisuke , Ura Takashi , Andoh Masashi , Muro Kei 
Published: February 2017

627 Background: Regorafenib improves survival in refractory metastatic colorectal cancer (mCRC), but alternative chemotherapy is required to avoid severe toxicity. S-1+oral leucovorin (SL) has shown promising results in untreated mCRC without severe toxicity. TML trial demonstrated that continuation of bevacizumab (Bev) after progression prolongs overall survival. Thus, we hypothesized that combination chemotherapy of SL/Bev would be beneficial; we conducted a single-center phase II trial to assess the efficacy and safety of SL/Bev as a salvage therapy in mCRC. Methods: Major eligibility criteria were: mCRC with confirmed adenocarcinoma diagnosis; age > 20 years; ECOG performance status, 0–2; and progression after administration or intolerance to approved drugs for mCRC (5-FU, oxaliplatin, irinotecan, Bev, and anti-EGFR antibody, if KRAS wild-type). S-1 (80–120 mg/body) and leucovorin (25 mg) were orally administered for 1 week followed by 1 week rest. Bev (5 mg/kg) was administered on day 1 of every 2-week cycle. Primary endpoint was disease control rate (DCR). Results: Twenty-three patients were enrolled: 8 (35%) females; median age, 70 years (range, 38–78); and 14 (61%) with KRAS wild-type. DCR was 65% [95% confidence interval (CI), 41.3–82.7%] and response rate was 6% (95% CI, 1.1–27.0%). One patient experiencing partial response to SL/Bev had BRAF mutant tumor with primary resistance to XELOX+Bev as first-line and irinotecan+cetuximab as second-line chemotherapy. Median progression-free and overall survival period were 4.1 and 9.5 months, respectively. Major adverse events were mucositis, (grade 3, 12%), diarrhea (grade 3, 12%), and decreased hemoglobin (grade 3, 12%). Conclusions: SL/Bev was well tolerated and delayed progression; therefore, it can be an alternative chemotherapy for refractory mCRC. We will report the data from final analysis at the meeting. Clinical trial information: 000009083.
The impact of dose reduction and time delay in irinotecan- and oxaliplatin-based chemotherapies on outcomes in metastatic colorectal cancer.
Authors: Mashita Naoki , Nakayama Goro , Hayashi Naomi , Tanaka Chie , Kobayashi Daisuke , Kanda Mitsuro , Yamada Suguru , Fujii Tsutomu , Sugimoto Hiroyuki , Koike Masahiko , Nomoto Shuji , Fujiwara Michitaka , Ando Yuichi , Kodera Yasuhiro 
Published: February 2017

631 Background: This study was designed to evaluate the influence of dose reduction and schedule modification on outcomes in patients with metastatic colorectal cancer (mCRC). Methods: Pooled datasets from two previous phase II trials of FOLFIRI (CCOG-0502; n = 36) and mFOLFOX6 (CCOG-0704; n = 30) in patients with mCRC were analyzed retrospectively. The RDIs of irinotecan and oxaliplatin were compared to response rate (RR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). To assess the effects of dose reduction and time delay, we defined ‘dose index (DI)’ as the ratio of the actual delivered total dose to the planned total dose and ‘time index (TI)’ as the ratio of the planned duration to the actual duration of therapy. Relative dose intensity (RDI) was computed by multiplying DI by TI. DI and TI of irinotecan and oxaliplatin were compared to response rate (RR), disease control rate (DCR) and progression-free survival (PFS). Results: In patients receiving FOLFIRI therapy, the median DI and TI of irinotecan were 0.92 and 0.90, respectively. RRs were 59% vs. 12% in the higher vs. lower DI groups (p < 0.01), and 35% vs. 35% in the higher vs. lower TI groups (p = 1.00), respectively. Median PFS was 10.2 vs. 5.0 months in the higher vs. lower DI groups (p < 0.01), and 6.1 vs. 6.7 months in the higher vs. lower TI groups (p = 0.48), respectively. In mFOLFOX6 therapy, the median DI and TI of oxaliplatin were 0.97 and 0.82, respectively. RRs were 44% vs. 36% in the higher vs. lower DI groups (p = 0.65), and 44% vs. 36% in the higher vs. lower TI groups (p = 0.65), respectively. Median PFS was 7.7 vs. 6.7 months in the higher vs. lower DI groups (p = 0.13), and 8.5 vs. 5.9 months in the higher vs. lower TI groups (p = 0.02), respectively. Multivariate analyses showed that DI of irinotecan (HR 8.48; 95% CI, 2.94-24.51, p < 0.01) and TI of oxaliplatin (HR 2.74; 95% CI, 1.02-7.33, p = 0.04) were the independent prognostic factors for PFS. Conclusions: Dose reductions in irinotecan and time delays in oxaliplatin could have significant impact on PFS in patients receiving FOLFIRI and FOLFOX6, respectively.
MD Anderson experience with off-study regorafenib in patients with advanced colorectal cancer.
Authors: Bugano Diniz Gomes Diogo , Hassabo Hesham M. , Al Mutar Salwan S. , Sahin Ibrahim Halil , Rogers Jane , Nguyen D. Van , Bolonesi Ryan M. , Pini Tunghi May , Dasari Arvind , Kopetz Scott , Overman Michael J. , Eng Cathy , Kee Bryan K. , Hassan Manal , Garrett Chris R. 
Published: February 2017

635 Background: Regorafenib was approved by the FDA on September 27, 2012 following the CORRECT trial demonstrating an overall survival (OS) benefit compared to placebo in pts with advanced treatment-refractory CRC (Grothey A. et al: Lancet. 2013;381:303-12). Little data exists regarding patient treatment outcomes outside of reported clinical trial data. Methods: Pts seen at MD Anderson Cancer Center with a diagnosis of gastrointestinal malignancies since October 1, 2012 were evaluated for regorafenib therapy; electronic clinic records were reviewed for pt treatment data, toxicity, and survival outcomes. Results: 61 pts were identified; 4 pts were determined to have GI malignancy other than CRC [appendiceal cancer (n=3) and duodenal cancer (n=1)] and were omitted from this analysis. Median age was 58 years (range 30.5-83.3), M:F 37:20 (65%:35%), KRAS non-mutant/ KRAS mutant 26/31 (46%:54%), BRAF mutant n=3 (5%); Median time from diagnosis of metastatic disease to initiation of regorafenib therapy was 27.7 months (range 5.9-112.3); 8 pts (14%) had enrolled in clinical trials prior to starting regorafenib. The initial starting dose was 160 mg (n= 38, 66.7%), 120mg (n=18, 31.5%), and 80mg (n=1, 1.8%) respectively. Dose reductions or interruptions were required in 25 pts (43.8%); 14 patients (24.5%) discontinued therapy due to toxicity. The most common grade 3 adverse event was hand-foot reaction (n=12; 21%). One pt initiated on 120 mg was able to tolerate dose escalation to 160mg. Seven pts (12.2%) had stable disease radiographically for more than 2 months and 2 had a confirmed partial response (3.5%). Median OS was 9.1 months (95% C.I. 5.3-12.8) and median time on regorafenib therapy was 2.2 months (range 0.2-10.3). Following regorafenib discontinuation 12 pts (21%) were enrolled on phase I trials. Conclusions: In this pt population palliative regorafenib therapy was associated with modest efficacy and significant toxicity. Dose reductions or interruptions were common (43.8%) even despite a large number of pts being initiated on a dose lower than the recommended initial dose (33.3%). Further studies may be required to determine the optimal tolerable dose in pts with advanced CRC.
Clinical outcomes for patients with liver-limited metastatic colorectal cancer: Arguing the case for specialist hepatobiliary multidisciplinary assessment.
Authors: Thillai Kiruthikah , Repana Dimitra , Korantzis Ippokratis , Prachalias Andreas , Kane Pauline , Ross Paul J. 
Published: February 2017

637 Background: In patients (pts) with liver-limited metastatic colorectal cancer (mCRC), surgical resection or radiofrequency ablation (RFA) can lead to a significant overall survival benefit. Specialist hepato-biliary (HPB) multidisciplinary meetings (MDMs) are currently believed to provide the best forum to discuss this cohort of pts and assess their suitability for surgery or RFA. Methods: A retrospective analysis was undertaken of pts diagnosed with liver-limited mCRC over a period of 6 months within a specified cancer network in the United Kingdom. In addition to discussed cases, pts who were diagnosed but not referred to the HPB MDM were also discussed within the MDM setting. For these pts, contributors were blinded and decisions were made regarding resectability and appropriateness for RFA based on patient imaging and clinical history. Results: In a six month period, 159 pts were diagnosed with liver-limited mCRC within our cancer network. Of these, 68 (43%) were referred at the time of initial diagnosis, with a further 38 (24%) referred after commencing systemic treatment. 35 (56%) who were discussed at the time of their original diagnosis went on to have either a hepatectomy or RFA, as did 18 (51%) patients referred after initiating systemic treatment. 81 pts (78%) referred to the HPB MDM had synchronous liver metastases. Of the remaining 53 (33%) patients who were not referred to the HPB MDM, the average age was 70.2 years and 38 (86%) had synchronous liver metastases. Imaging was available for 31 (58%) of these pts. Decisions regarding resectability or RFA were made within the MDM based solely on history and radiology findings. Of these cases, 13 (41.9%) were identified as resectable or potentially resectable and 11 (35.5%) may have been suitable for a clinical trial. None of these 31 pts (100%) had hepatic surgery or RFA. Conclusions: Whilst the majority of pts with liver-limited mCRC were referred appropriately, this study highlights that a number of pts with potentially resectable disease are not being discussed at a specialist HPB MDM. A review of all diagnosed cases would ensure that an increased number of pts are offered hepatic resection or RFA.
Tumor angiogenesis genotyping and efficacy of first-line chemotherapy in metastatic gastric cancer patients.
Authors: Scartozzi Mario , Giampieri Riccardo , Loretelli Cristian , Bittoni Alessandro , Mandolesi Alessandra , Faloppi Luca , Del Prete Michela , Bianconi Maristella , Andrikou Kalliopi , Bearzi Italo , Cascinu Stefano 
Published: February 2017

64 Background: An altered expression of tumour angiogenesis-related factors has been constantly associated to a more aggressive phenotype and an increased relapse rate in several tumour types, including gastric cancer. Besides correlating with prognosis, tumour-driven angiogenesis seemed also able to influence response/resistance to chemotherapy in pre-clinical models. We examined the role of tumour angiogenesis genotyping in determining clinical outcome in metastatic gastric cancer patients receiving first-line chemotherapy. Methods: VEGF-A, VEGF-C, FLT1, KDR and FLT4 genotyping was performed on gastric tumours from 94 consecutive patients receiving platinum-based first-line chemotherapy. Results: Only theVEGF A rs25648 correlated with RR (PR = 18% among patients showing the VEGF A rs25648 CT or TT genotype vs. 44% among patients showing the VEGF A rs25648 CC genotype, p = 0.04). The VEGF A (rs2010963) and VEGF C (rs4604600 and rs7664413) correlated with mPFS and the VEGF A rs25648 and FLT4 rs307833 correlated with both mPFS and OS. Among other clinical variables tested (sex, age, ECOG performance status, gastrectomy, adjuvant chemotherapy, metastatic sites and second-line chemotherapy) only the use of second-line chemotherapy correlated with improved overall survival (10.2 months vs. 6.3 months for patients who received or did not receive second-line, p= 0.003). At multivariate the VEGF A rs25648 maintained an independent role in determining both median PFS (HR = 1.65 95% CI: 1.12-2.78, p= < 0.0001) and OS (HR = 1.58, 95% CI: 1.17-2.65, p = 0.0003). The use of second-line chemotherapy also showed an independent role in determining median OS (HR = 0.58, 95% CI: 0.38-0.87, p= 0.003). Conclusions: VEGF A rs25648 genotyping may help identifying a patients subgroup unlikely to benefit from a first-line, platinum-based combination and potentially candidate to alternative therapy choices. Our data may help designing future clinical trials with the aim to investigate the outcome of different chemotherapy regimens in different patients groups prospectively stratified according to angiogenesis profile.
Incidence of methacronous cancer after total colectomy with ileorectal anastomosis or total proctocolectomy in classical FAP patients.
Authors: Aguiar Samuel , Stevanato Paulo Roberto , Ferreira Fabio Oliveira , Santos Erika Maria Monteiro , Batista Ranyell Spencer Sobreira , Lopes Ademar 
Published: February 2017

646 Background: Total proctocolectomy (TPC) with ileal pouch is considered the procedure of choice in classic familial adenomatous polyposis (FAP), but total colectomy (TC) with rectal sparing can be performed in selected cases. The objective of this study is to determine and compare the incidence of methacronous cancer in the remanescent rectum in patients submitted to TPC or TC. Methods: We performed a retrospective analysis of 55 patients operated beteween 1992 and 2011. Patients were identified from 34 FAP families, registered at the AC Camargo Hereditary Colorectal Cancer Registry. Patients with attenuated FAP were excluded. The main endpoint was the occurence of cancer at the remanescent rectum. Results: Thirty seven patients were submitted to TPC and 18 to TC with ileo-rectal anastomosis. Among patients submitted to TPC, just one (2.7%) had methacronous adenocarcinoma just above the dentate line. Among patients submitted to TC with rectal sparing, 4 (22.2%) have another cancer at the remanescente rectum. This difference was statistically significant (0.035). The stage was initial in all cases, and all patients were submitted to salvage surgery. No deaths related to rectal cancer had occured. Conclusions: Surgical treatment of classical FAP still remains proctocolectomy with ileal pouch, whenever possible. Considering that methacronous cancer uses to be detected in initial stages, rectal sparing can be considered in very selected cases of classical FAP.