bluuebunny/crossref_metadata_2025_split huggingface dataset:
Residual rectal cancer after preoperative radiochemotherapy (ypT1-2): An indication for local excision instead of radical surgery?
Authors: Sprenger Thilo , Rothe Hilka , Conradi Lena-Christin , Homayounfar Kia , Beissbarth Tim , Ghadimi B. Michael , Liersch Torsten 
Published: February 2017

546 Background: Preoperative radiochemotherapy (RCT) followed by total mesorectal excision (TME) has improved local tumor control and led to a significant tumor downstaging. For patients with pathologic complete response (ypT0) as well as residual tumor restricted only to the bowel wall (ypT1-2) local excision has increasingly been discussed to avoid significant morbidity and functional deficits associated with TME. Therefore we investigated the incidence, distribution and tumor-related localization of mesorectal lymph node (LN) metastases in TME specimens with ypT0, ypT1-2 and ypT3-4 rectal cancers, respectively. Methods: TME specimens from 81 patients with locally advanced rectal cancer treated with neoadjuvant RCT within the phase III German Rectal Cancer Trial CAO/ARO/AIO-04 were evaluated. The entire mesorectal compartment was screened microscopically after complete paraffin embedding. The number and localization of all detectable LN metastases was specified in relation to the primary tumor. Results: Whereas 50 patients (62%) had ypT3-4 carcinomas after neoadjuvant RCT 20 patients (25%) presented with residual tumor within the bowel wall (ypT1-2). 11 patients (14%) had pathologic complete response (ypT0). 28 ± 13.7 LN were detected per specimen. 25 patients (31%) had residual LN metastases after RCT. Although the incidence was higher in the ypT3-4 group (40% ypN+) still 25% of patients in the ypT1-2 group had a mean number of 2.2 residual LN metastases. 55% of these metastases were located afar from the primary lesion in the proximal mesorectum. No patient with ypT0 status had residual LN metastases. Conclusions: Even in patients with good response and tumors restricted only to the bowel wall (ypT1-2) after RCT there is a considerable risk for residual LN metastases. The majority of metastases were located clearly outside the tumor region. Local excision of residual rectal cancer would be accompanied by a higher rate of local failure and radical surgery with TME should remain the standard treatment in those patients.
A mapping algorithm of health preferences from EORTC QLQ C30 to health utility index mark 3 (HUI3) in advanced colorectal cancer.
Authors: Chan Kelvin K. , Tu Dongsheng , O'Callaghan Christopher J. , Au Heather-Jane , Leighl Natasha B. , Brundage Michael Donald , Jonker Derek J. , Karapetis Christos Stelios , Ringash Jolie , Zalcberg John Raymond , Hoch Jeffrey S. , Tebbutt Niall C. , Shapiro Jeremy , Price Timothy Jay , Pavlakis Nick , Van Hazel Guy A. , Mittmann Nicole 
Published: February 2017

547 Background: The National Cancer Institute of Canada CO17 study, which showed that patients with advanced colorectal cancer had improved overall survival and derived health related quality of life benefits (measured with EORTC QLQ C30) when treated with cetuximab, collected health preferences with HUI3 prospectively. We examined the relationship between baseline health utilities and quality of life, and constructed a mapping algorithm to derive health utilities from EORTC QLQ C30. Methods: Data from 545 patients including baseline characteristics (age, gender, treatment arm, K-ras, ECOG PS, etc.), health preferences (HUI3), EORTC QLQ C30 five function scales, a two-item global health status (GHS) scale, three symptom scales, and six single items were obtained from the CO17 dataset. Correlations among HUI3 and EORTC QLQ C30 scales and baseline characteristics were examined. Multivariable linear regression model was constructed to develop a mapping algorithm to derive HUI3 from EORTC QLQ C30 scales and/or baseline characteristics. Leave-one-out cross validation (LOOCV) mean absolute error (MAE) and root mean square error (RMSE) were calculated to examine predictive ability. Results: The mean HUI3 was 0.717 (SD = 0.235). HUI3 was significantly correlated with baseline ECOG PS, number of disease sites and the presence of liver metastasis, but not with age, gender, treatment arms or K-ras. HUI3 was also significantly correlated with all EORTC QLQ C30 scales except the diarrhea scale. Multivariable regression showed that HUI3 remained significantly associated with four of the five functional scales (physical, role, cognitive and emotional), the pain scale and the GHS scale. A mapping algorithm consisting of these 6 scales resulted in a model with an adjusted R2 of 0.61, and LOOCV mean error of -0.00014, MAE of 0.11, and RMSE of 0.15. Conclusions: Health preferences as measured by HUI3 are significantly associated with HRQL as measured by EORTC QLQ C30 in patients with advanced refractory colorectal cancer. Our mapping will allow for the generation of health preference values in advanced colorectal cancer when only EORTC QLQ C30 results exist in order to conduct cost-effectiveness analysis.
Phase I trial of FOLFIRI in combination with sorafenib and bevacizumab in patients with advanced gastrointestinal malignancies.
Authors: Hubbard Joleen Marie , Kim George P. , Borad Mitesh J. , Qin Rui , Lensing Janet , Wright John Joseph , Erlichman Charles , Grothey Axel 
Published: February 2017

551 Background: Sorafenib inhibits various pro-angiogenesis pathways including PDGFR-B, a factor associated with resistance to anti-VEGF therapy. A previous phase II trial in patients with chemorefractory metastatic CRC demonstrated a 63% disease control rate with a combination of bevacizumab (BEV) and sorafenib. This phase I trial sought to determine the MTD of BEV and sorafenib combined with standard cytotoxic therapy for advanced gastrointestinal (GI) cancers. Methods: Patients with advanced GI malignancies appropriate for irinotecan-based therapy were enrolled (14 with CRC, 3 gastroesophageal). A standard 3 + 3 design was used with 3 escalating sorafenib dose levels (DL): (1) 200 mg po daily, days 3-7, 10-14; (2) 200 mg po twice daily, days 3-6, 10-13; and (3) 200 mg po twice daily, days 3-7, 10-14. FOLFIRI: irinotecan 180 mg/m2 d1, leucovorin 400 mg/m2 d1, 5-fluorouracil (FU) bolus 400 mg/m2 d1, 5-FU infusion 2400 mg/m2d1-2 and BEV 5 mg/kg d1. 1 cycle = 14 days. Results: Seventeen pts were enrolled, median age of 56 (range 32 and 81). Two pts were replaced, as they did not complete DLT evaluation, leaving 15 evaluable pts. Four evaluable pts at DL1 and 6 pts at DL2 had no DLTs. At DL 3, the first cohort of 3 pts did not experience any DLTs. In the second cohort of 3 pts, 2 pts experienced DLTs (asymptomatic G3 hypophosphatemia, G3 dehydration and diarrhea). MTD was determined to be DL2: sorafenib 200 mg PO twice daily, days 3-6, 10-13 combined with FOLFIRI and BEV at standard doses. Of the 15 evaluable pts, 4 pts had PR, 8 pts had SD as best response, 1 pt had PD, and 2 pts discontinued treatment prior to first tumor assessment. The median number of cycles was 10 (range 1-37). Three pts with CRC had disease control > 12 months. Conclusions: The MTD of this regimen is sorafenib 200 mg PO twice daily, days 3-6,10-13 combined with standard doses of FOLFIRI and BEV. Dual VEGF inhibition combined with cytotoxic therapy may provide prolonged disease stabilization for select patients with advanced GI malignancies. Supported by CA69912 and CA15083. Clinical trial information: NCT01383343.
Multi-institutional assessment of sphincter preservation for rectal cancer.
Authors: Abdelsattar Zaid M. , Wong Sandra L. , Birkmeyer Nancy J. , Cleary Robert K. , Times Melissa L. , Figg Ryan E. , Peters Nanette , Krell Robert W. , Campbell Darrell A. , Hendren Samantha K. 
Published: February 2017

566 Background: Rates of sphincter preserving surgery (SPS) have been proposed as a quality measure for rectal cancer (RC) surgery. However, administrative and registry-based SPS rates often lack critical patient and tumor characteristics, rendering it unclear if variations in SPS rates are due to unmeasured case-mix differences or selection criteria. The aim of this study was to determine whether hospitals’ SPS rates differ after accounting for clinical characteristics. Methods: As part of a RC quality project, 10 hospitals in the Michigan Surgical Quality Collaborative retrospectively collected RC-specific data from 2007-2012. We assessed for SPS predictors using multivariable regression. Patients were categorized as “definitely SPS eligible” a priori if they did not have any of the following: poor sphincter control, stoma preference, sphincter involvement, tumor <6 cm from the anal verge (an intentionally conservative cutoff) or metastatic disease. We compared hospital performance with and without these clinical data using Spearman’s correlations. Results: In total, 349 patients underwent surgery for RC in 10 hospitals (5/10 high volume and 6/10 major teaching). Of those, 74% had SPS (range by hospital 50%-91%). On multivariable analysis, only pre-op radiation, tumor location, hospital teaching status and hospital ID were independent predictors of SPS, but not age, sex, BMI, AJCC stage, ASA class, or hospital CRC surgery volume. Analyses of the “definitely eligible” patients revealed an overall SPS rate of 88% (65-100%). Hospital SPS rankings using crude versus clinically-adjusted SPS rates proved to be highly correlated (Spearman’s ρ= 0.9). Tumor locations suggest differing selection criteria for SPS in different hospitals (Table). Conclusions: Rates of SPS vary by hospital, even after correcting for clinical characteristics using detailed chart review. These data suggest missed opportunities for SPS, and refute the general hypothesis that hospital variation in SPS rates in previous studies is due to unmeasured case-mix differences. [Table: see text]
HER2 and HER3 expression in hepatic metastases of colorectal cancer: New targets for specific treatment approaches?
Authors: Conradi Lena-Christin , Styczen Hanna , Sprenger Thilo , Wolff Hendrik A. , Middel Peter , Nagelmeier Iris , Rüschoff Josef , Homayounfar Kia , Ghadimi B. Michael , Beissbarth Tim , Liersch Torsten 
Published: February 2017

567 Background: Even though treatment options for coloretal cancer liver metastases have improved with the implementation of multimodal strategies and new agents, progression of distant metastases is still limiting the prognosis of affected patients. In this context we investigated the expression of HER2 and HER3 in patients with metastatic colorectal cancer and primary tumors. Methods: In this study 226 consecutive patients with hepatic metastases of colorectal cancer were included. HER2 and HER3 expression were determined in the tissue from resected metastases and—if available—in primary tumors. Immunohistochemical scoring (IHC 0 to IHC 3) and S-ISH-amplification-detection (for HER2) were used to determine the HER2 and HER3 status. Results: A positive HER2 status was found in 8.4% of all hepatic metastases; an overexpression of HER-3 in 74,8% of all cases. There was a high congruence of the expression pattern of HER2 and HER3 between hepatic metastases and available primary tumors (>90%). Conclusions: HER2 amplification and HER3 overexpression is detectable in a significant proportion of hepatic metastases of colorectal cancer. These results suggest that innovative new targeted treatment agents might be possible opportunities for the specific therapy of patients with HER2/HER3 positive metastatic colorectal cancer and should be further assessed within prospective clinical trials.
Prognostic value of the number of retrieved lymph node and lymph node ratio in locally advanced rectal cancer after preoperative radiation therapy.
Authors: Park Jin-hong , Shin Young Seob , Choi Eun Kyung , Ahn Seung Do , Yoon Sang Min , Kim Jong Hoon 
Published: February 2017

582 Background: To assess the prognostic impact of total number of retrieved lymph node (TNN) and lymph node radio (LNR) in patients with locally advanced rectal cancer who received preoperative radiation therapy and surgery Methods: We retrospectively analyzed data from 677 patients with locally advanced rectal cancer who underwent preoperative radiation therapy followed by mesorectal excision at Asan Medical Center between October 1999 and May 2009. The median radiation dose was 50 Gy, and 674 patients (99%) underwent concurrent chemotherapy. All patients were divided into two groups according to the status of lymph node involvement. We assessed the influence of TNN on overall survival (OS) and disease-free survival (DFS) in the patients with node-negative disease (pN0, n = 490), and the prognostic value of LNR, estimated by dividing the number of positive nodes by the number of lymph nodes examined, in the patients with node-positive disease (pN1-2, n = 187). Results: The median follow-up period was 74 months.Patients with pN0 had median 12 lymph nodes examined (range, 0-38). Comparing with patients who had ≤ 8 TNN, patients with > 9 TNN had significantly higher 5-year OS (89% vs. 95%, p = 0.038) and DFS rates (81% vs. 90%, p = 0.013). Multivariate analysis showed that TNN more than 9 was significant prognostic factor for OS (p = 0.032) and DFS (p = 0.007). For patients with pN1-2, patients with low LNR (≤ 0.33, n = 144) showed significantly higher 5-year OS (33% vs. 73%, p < 0.001) and DFS rates (18% vs. 56%, p < 0.001) than high LNR group (> 0.33, n = 43). Also, low LNR was independent prognostic factor for OS (p = 0.001) and DFS (p < 0.001) in multivariate analysis. Conclusions: TNN for node-negative rectal cancer and LNR for node-positive rectal cancer are independent prognostic factors for survival outcome in patients with locally advanced rectal cancer after preoperative radiation therapy. These factors could be considered as useful prognostic indicators irrespective of current TNM staging system.
Comparing outcomes and toxicities from intensity-modulated radiation therapy and three-dimensional conformal radiation therapy for anal cancer: Is one really better?
Authors: Fredman Elisha T. , Kumar Aryavarta M. S. , Abdel-Wahab May 
Published: February 2017

589 Background: Intensity-modulated radiation therapy (IMRT) has largely supplanted 3-dimensional conformal radiation (3D-CRT) for definitive treatment of anal cancer due to its decreased toxicity and potentially improved outcomes. Convincing data directly demonstrating its advantages, however, remain limited. We compared outcomes, acute, and post-treatment toxicity of patients with anal cancer treated with concurrent chemotherapy and IMRT vs. 3D-CRT. Methods: We performed a single institution retrospective review of patients treated with IMRT or 3D-CRT as part of definitive Mitomycin-C/5-FU based chemoradiation for anal cancer from January 2003-December 2012. Results: 61 and 104 patients received IMRT and 3D-CRT respectively. Overall, 92.7% had squamous cell carcinoma. The mean pelvic dose before boost was 48.3Gy and 44Gy for IMRT and 3D-CRT respectively. Complete response, partial response, and disease progression rates were similar (83.6%, 8.2%, 8.2% for IMRT; 85.6%, 6.7%, 7.7% for 3D-CRT; p = ns). There was no significant difference in overall survival (p = 0.971), event free survival (p = 0.900), and local or distant recurrence rates (p = 0.118, p = 0.373). IMRT caused significantly less acute grade 1-2 incontinence (p = 0.035), grade 3-4 pain (p = 0.033) and fatigue (p = 0.030). Patients receiving IMRT had significantly fewer post-treatment toxicities (p = 0.008), outperforming 3D-CRT in 7/8 toxicities reviewed. Though total length of treatment was comparable between IMRT and 3D-CRT (43.6 and 44.5 days), the IMRT group had fewer, shorter treatment breaks (p = ns). Conclusions: This report represents the largest series directly comparing concurrent chemotherapy with IMRT vs. 3D-CRT for definitive treatment of anal cancer. IMRT significantly reduced acute and post-treatment toxicities and allowed for safe and effective pelvic dose escalation.
Prognostic factor of resection of hepatic and pulmonary metastases from colorectal cancer: A multi-institutional questionaire study.
Authors: Itabashi Michio , Hirosawa Tomoichiro , Ubukata Mamiko , Ihara Takeshi , Makao Sayumi , Kaji Sanae , Bamba Yoshiko , Hashimoto Takuzou , Ogawa Shimpei , Sugihara Kenichi , Kameoka Shingo 
Published: February 2017

590 Background: Resection of hepatic or pulmonary metastases (HPM) has been accepted as appropriate therapy. However whether aggressive surgery of both hepatic and pulmonary metastases from colorectal cancer (CRC) is of value has not been verified in detail. Methods: 1,179 patients undergone complete pulmonary resection were collected from 110 institutions by the 78th Congress of the Japanese Society of Cancer of the Colon and Rectum. Data on 209 of 1,179 patients who had undergone resection of HPM from CRC were included in this study. Results: (1) Outcome of surgery: In 970 patients undergoing pulmonary resection alone, 5-year relapse free survival and 5-year survival after pulmonary resection were 41.9% and 65.3%. In 209 patients undergoing hepatic and pulmonary resection, 5-year relapse free survival and 5-year survival after pulmonary resection were 33.5% (p = 0.0016) and 57.8% (p = 0.0021). The outcomes after resection were significantly better in patients with sequentially detected metastases (5-year survival of 71.6%) than in those with simultaneously detected ones (5-year survival of 41.5%) (p = 0.0016). (2) Prognostic factor:Univariate analysis revealed three variables. These were the disease free interval less than 2 years from CRC surgery to pulmonary resection (DFI) (p = 0.005), lymph node metastases of original site (p = 0.01) and extent of hepatic metastases (p = 0.01). The other factors were not statistically significant for prognosis. Multivariate analysis revealed two variables that were major prognostic factors. These were DFI (p = 0.003), and lymph node metastases of original site (p = 0.0019). Conclusions: Resection of HPM from CRC may help to prolong the survival. Independent, significant prognositic factors were lymph node metastases of original site and the DFI from CRC surgery to pulmonary resection.
Natural history of venous thromboembolism in gastrointestinal cancers.
Authors: Metcalf Robert Lewin , Hopley Nicholas , Henry Thomas , Hasan Jurjees 
Published: February 2017

593 Background: Venous thromboembolism (VTE) is a leading cause of mortality in patients with cancer. Characterisation of VTE in cancer will guide prophylactic anti-coagulation of high risk populations. Methods: We performed a retrospective analysis using electronic patient records, of 910 upper GI (UGI) cancer and 1,299 colorectal cancer (CRC) patients referred to a tertiary cancer centre to identify the incidence of VTE, its relationship to chemotherapy and impact on survival. VTE risk scores were calculated using the Khorana index (Khorana AA et al. Blood 2008 May 15;111(10):4902-7). Results: VTE were identified in 88/910 (9.7%) patients with UGI cancer (oesophageal 37%, gastro-oesophageal 24%, gastric 39%), comprising 50 deep vein thromboses (DVT) and 43 pulmonary emboli (PE). 52% were stage I-III and 48% stage IV. 56% of patients received chemotherapy up to 4 weeks before VTE. Median time to VTE from cancer diagnosis was 5.3 months (range -3 to 31.2). No difference in survival was seen for patients with VTE compared to a stage matched control group without VTE (median OS 12.5 v 9.4 months, log rank p=0.2). VTE (DVT:PE, 69:49) affected 115/1299 (8.9%) patients with CRC (25% stage I-III, 75% stage IV). Median time to VTE from CRC diagnosis was 5.4 months (range -4.3 to 54.5) for stage I-III and 8.6 months (range -4.3 to 77) for stage IV CRC. Chemotherapy was received by 41% (stage I-III) and 78% (stage IV) of patients within 4 weeks before VTE. Data to perform VTE risk score were available for 72/115 CRC patients with VTE, which classified 61.1% as low-risk (stage I-III 81.2% (13/16); stage IV 55.3% (31/56)). Again, no difference in survival was seen for patients with VTE compared to a control group without VTE matched for stage and performance status (median OS for stage I-III, 40 vs. 50.3 months p=0.41; stage IV, 20.7 vs. 18.8 months, p=0.52). Conclusions: VTE affects nearly 1 in 10 patients with GI cancer receiving chemotherapy. The peak incidence is in the first 6 months following diagnosis. Most patients have DVT and 36% are asymptomatic. No adverse impact on survival was seen for patients with VTE compared to stage matched controls implying VTE is not a prognosticator of poor outcomes in gastrointestinal cancers. Mature data will be presented at the meeting.
Comparison of adding cetuximab (Cmab) or panitumumab (Pmab) to irinotecan (IRI)-based chemotherapy in salvage line against KRAS wild-type patients with metastatic colorectal cancer (mCRC): Analysis of HGCSG0901 and 1002.
Authors: Fujikawa Koshi , Yuki Satoshi , Sasaki Takahide , Takahashi Yasuo , Iwanaga Ichiro , Uebayashi Minoru , Saitoh Soh , Koike Masahiko , Nakamura Michio , Sato Yasushi , Kudo Mineo , Tateyama Miki , Kawamoto Yasuyuki , Hisai Hiroyuki , Saito Mayuko , Onodera Manabu , Takagi Tomofumi , Sakata Yuh , Komatsu Yoshito 
Published: February 2017

598 Background: Cmab and Pmab have antitumor activity and acceptable safety profiles in patients (pts) with mCRC. Although IRI-based chemotherapy combined with Cmab or Pmab has demonstrated the effectiveness in salvage-line, there has been no reported trials comparing these antibodies directly. Methods: Data of 96 pts with mCRC treated by Cmab plus IRI-based chemotherapy (Cmab/IRI) from HGCSG 0901 and 27 pts treated by Pmab plus IRI-based chemotherapy (Pmab/IRI) from HGCSG1002 were retrospectively analyzed. All patients with KRAS wild type were refractory to or intolerant for 5-FU/ irinotecan/ oxaliplatin and also were never administered anti-EGFR-antibodies. Survival analyses were performed with Kaplan-Meier method, log-rank test and Cox proportional hazards model. Results: Patient characteristics were as below (Cmab/IRI vs. Pmab/IRI); male/female 58/38 vs. 16/11, median age (range) 63(38-80) vs. 64(49-81), PS 0/1/2 52/35/9 vs. 21/6/0, number of metastatic organs 1/2/3- 29/37/30 vs. 6/12/7, prior bevacizumab administration 62.5% vs. 92.6% (p = 0.002). MST was 9.9 months in the Cmab/IRI and 14.9 months in the Pmab/IRI (p = 0.196). PFS was 4.8 months in the Cmab/IRI, as compared with 5.4 months in the Pmab (p = 0.083); the corresponding RR was 25.0 % and 18.5% (p = 0.611). After adjusting other prognostic factors with Cox proportional hazard model, the administration of Cmab/Pmab made significant difference neither for OS (HR 0.908, 95% CI 0.513-1.610, p = 0.742), nor PFS (HR 0.732, 95% CI 0.447-1.199, p = 0.732). Conclusions: In this integration analysis of two studies, there were no significant difference in efficacy between Cmab and Pmab with IRI-based chemotherapy in the salvage-line treatment of pts with mCRC.