bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of objective response and overall survival in patients with inoperable or metastatic gastric and esophagogastric junction (EGJ) cancer: Landmark analysis of 10-year data from first-line clinical trials.
Authors: Bolt Toki Anna , Pauligk Claudia , Werner Dominique , Hofheinz Ralf Dieter , Mayer Frank , Luley Kim Barbara , Homann Nils , Schmalenberg Harald , Egger Matthias , Al-Batran Salah-Eddin
Published: February 2017

57

Background: The aim of the study is to determine whether the achievement of an objective response to 1st line chemotherapy is prognostic of patient’s outcome in gastric/EGJ adenocarcinoma. Methods: Individual patient (pts) data from prospective 1st line trials conducted by a single study group were used. Response data, pts’ characteristics, type of chemotherapy and overall survival (OS) data were analyzed. Responses were evaluated according to WHO criteria in all trials and landmark analysis conducted. Results: Response rates were complete (CR) in 3.1%, partial (PR) in 37.7%, stable disease (SD) in 33.8% and progressive disease (PD) in 15.4% pts (9.9% were not evaluable). Overall response rate (OR= CR + PR) was 40.8%. Median OS in pts with CR vs. PR vs. SD vs. PD were 28.9 vs. 14.8 vs. 10.8 vs. 5.2 months, respectively; p= 2.6 x 10-42. OR also strongly predicted OS (16.7 vs. 8.6 months in pts with vs. no OR; p= 9.0 x 10-14). Landmark studies were established with landmarks set on 2 and 4 months. Median OS at landmark point 2 months in pts with CR vs. PR vs. SD vs. PD were 17.3 vs. 14.5 vs. 11.1 vs. 5.4 months, respectively; p= 3,7 x 10-12. Pts with OR vs. no OR had a median OS of 14.7 vs. 10.9 months, p= 0.0001. Median OS at landmark point 4 months in pts with CR vs. PR vs. SD vs. PD were 23.9 vs. 14.8 vs. 11.8 vs. 7.7 months, respectively; p= 1.2 x 10-10. Pts with OR vs. no OR had a median OS of 16.1 vs. 11.1 months, p= 7.0 x 10-6. OR remained the strongest predictor of OS in the multivariate analysis (p= 6.3 x 10-7) followed by the presence of non-regional LN as the only site of metastasis (p= 8.2 x 10-5) and ECOG (p= 0.002). Conclusions: The achievement of an objective response is the strongest predictor of survival in pts with gastric and EGJ cancer and could serve as surrogate marker if validated.
Phase I drug-interaction study of effects of calcium and magnesium infusions on oxaliplatin pharmacokinetics and acute neurotoxicity in colorectal cancer patients.
Authors: Han Catherine HyeWon , Khwaounjoo Prashannata , Kilfoyle Dean H. , Hill Andrew Graham , McKeage Mark James
Published: February 2017

578

Background: Calcium and magnesium (Ca/Mg) infusions have been suggested as an effective intervention for preventing oxaliplatin-induced neurotoxicity, but the effects of Ca/Mg infusions on oxaliplatin pharmacokinetics, motor nerve hyperexcitability, and acute neurotoxicity symptoms are unclear. Methods: In this double-blind crossover study, colorectal cancer patients undergoing oxaliplatin-based chemotherapy were randomised to receive Ca/Mg (1g Ca Gluconate plus 1g MgSO4) on cycle 1 and placebo (vehicle alone) on cycle 2, or to receive the same treatments in the opposite sequence. Study endpoints included plasma pharmacokinetics of intact oxaliplatin and free platinum; electromyography (EMG) detection of abnormal spontaneous high-frequency motor unit action potential discharges; and patient-reported acute neurotoxicity symptoms and their preferred study treatment for reducing these symptoms. Results: The planned accrual target was achieved. Nineteen of 20 enrolled patients completed the study. Plasma pharmacokinetics of intact oxaliplatin and free platinum were similar when oxaliplatin was given with Ca/Mg or placebo (ratio of geometric means of AUC0-t with Ca/Mg or placebo: intact oxaliplatin, 0.95 (90% CI, 0.90 – 1.01); free platinum, 0.99 (90% CI, 0.94 – 1.05)). EMG motor nerve hyperexcitability scores were similar with Ca/Mg and placebo (mean difference in EMG score between Ca/Mg and placebo: -0.3 (95% CI, -2.2 – 1.6)). Patient-reported acute neurotoxicity symptoms were similar in frequency with Ca/Mg and placebo. For reducing neurotoxic symptoms, fewer patients preferred Ca/Mg than placebo or neither treatment (26% versus 74%; p < 0.01). Conclusions: Ca/Mg infusions do not alter the clinical pharmacokinetics of oxaliplatin and do not seem to reduce its acute neurotoxicity. Clinical trial information: ACTRN12611000738921.
Resection of colorectal cancer (CRC) metastases in routine practice.
Authors: Tran Ben , Wong Hui-li , Field Kathryn Maree , Tie Jeanne , Shapiro Jeremy David , Wong Rachel , Yip Desmond , Nott Louise M. , Richardson Gary Edward , McKendrick Joseph James , Gibbs Peter
Published: February 2017

599

Background: The optimal management of metastatic colorectal cancer (mCRC) involves a multimodality approach. Complete resection of limited metastatic disease is a critical, potentially curative intervention for a minority of patients (pts). Data on resection rates and outcomes in routine clinical practice are limited. Methods: Analysis of pts prospectively entered onto the TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) database, a multisite Australian mCRC registry. Data collection commenced in July 2009 and is ongoing at 14 centres. Treatment intent was recorded at initial pt review as curative, potentially curative or palliative. Results: At median follow-up of 20.9 months, 213 (21%) of 1,012 pts have undergone metastasectomy, including 179 (84%) R0 resections. Liver (55.4%) and lung (20.2%) were the commonest resected disease sites. For 26 (12.2%) pts the initial treatment intent had been palliative. Pts who had metastases resected were younger (median age 63 vs. 70 years, p<0.0001), of better performance status (PS0-1: 97.7 vs. 75.5%, p<0.0001), had fewer comorbidities (Charlson Index ≤3: 75.1 vs. 55.9%, p<0.0001) and fewer sites of disease (single site: 79.8% vs. 52.5%, p<0.0001). A significantly higher proportion of pts treated in private than public hospitals underwent resections: 143/548 (26.1%) vs. 70/459 (15.3%), p<0.0001. At initial presentation, more private pts had PS0-1 (82.8% vs. 77.8%, p=0.0459) and single disease site (61.3% vs. 54.5%, p=0.0291) than public pts, but the median age of private pts was higher (70 vs. 67 years, p=0.041). Overall survival was equivalent for resected pts in both groups (median not reached, HR 0.96, 95% CI 0.45-2.06, p=0.9189). Conclusions: A substantial proportion of mCRC pts in routine practice undergo resection of distant metastases, including some pts initially considered incurable. Significant variation between sites has been noted, which may relate to differences in pt population and/or a more aggressive treatment approach. Multivariate analyses and review of individual centre data are planned to explore reasons for potential underutilization of this critical intervention.
Molecular testing guidelines for selection of colorectal cancer patients for targeted and conventional therapies.
Authors: Sepulveda Antonia R. , Hamilton Stanley R. , Grody Wayne
Published: February 2017

600

Background: Molecular testing to enhance the response of colorectal cancers (CRC) to targeted and conventional therapies has been the center of many recent studies. While testing for KRAS mutations is generally accepted as a requirement to select patients for anti-EGFR antibody therapies, evidence-based guidelines for other markers are needed. The objective of this project is to establish evidence-based recommendations for the molecular testing of CRC tissues to guide EGFR-targeted therapies and conventional chemotherapy regimens. Methods: Three professional societies: American Society of Clinical Pathologists (ASCP), College of American Pathologists (CAP) and the Association for Molecular Pathology (AMP) have selected co-chairs, and multidisciplinary expert and advisory panels, which include specialists in pathology, GI oncology, surgery, gastroenterology and genetics. A systematic review was designed based on five overall key questions: (1) What biomarkers are useful for CRC management (selection of patients for targeted and conventional therapies)? (2) How should tissue specimens be processed for biomarker testing for CRC management?; (3) How should biomarker testing for CRC management be performed? (4) How should molecular testing of CRC be implemented and operationalized?; V: Should other genes/biomarkers be routinely tested? The expert panel will review title-abstract (TA) and full-text (FT) in DistillerSR software. Data extraction will then be performed and the panel will draft recommendations based upon evidence tables and the considered judgment process. Results: A systematic review was performed to capture published articles from January 2009 through August 2013, yielding 2,883titles to date. Currently the TA review phase is in course. Release of draft recommendations during an open comment period is anticipated in early 2014. Conclusions: The ASCP-CAP-AMP Molecular Testing Guidelines for Selection of Colorectal Cancer Patients for Targeted and Conventional Therapies will provide evidence-based guidelines for molecular testing of CRC. The final publication release is anticipated for the fall 2014.
A phase II trial of metformin and fluorouracil (MetFU) for patients (pts) with metastatic colorectal cancer (mCRC) refractory to standard treatment.
Authors: Miranda Vanessa Costa , Faria Luiza Dib , Braghiroli Maria Ignez Freitas Melro , Jacobs Monica , Sabbaga Jorge , Hoff Paulo Marcelo , Riechelmann Rachel Pimenta
Published: February 2017

601

Background: Pts with mCRC whose disease progressed after 5-FU, oxaliplatin, irinotecan and monoclonal antibodies have an unmet medical need. There is growing evidence suggesting an antitumoral effect of metformin in several tumor types, including CRC. Methods: Our primary objective was to evaluate the efficacy and safety of MetFU in heavily pretreated CRC pts with current progressive disease Last dose of 5-FU was administred at least 4 months prior to enrollment. Efficacy was defined as disease control rate at 8 weeks, using RECIST 1.1. Secondary endpoints were progression free survival, overall survival and tolerability. Single-arm Simon two-stage phase II trial was used. The treatment consisted of metformin 850 mg bid continuously plus 5-FU 425mg/m2 + Leucovorin (LV) 50 mg weekly for 4 weeks until disease progression, unacceptable toxicity or consent withdrawn in pts with mCRC who had progressed to conventional lines of treatment. Results: In the first stage, 22 pts were included: 12 pts (54%) were men, median age was 55 years and 59% were classified as an ECOG 1.14 pts faced treatment adverse events and 4 pts were excluded due to toxicity G3/4 - 2 pts had thrombocytopenia and 2 had limiting fatigue. Median time on treatment was 3.8 months, and 17 pts were evaluable for response: 6 pts (27%) had stable disease at 8 weeks as best response, with a median progression free survival (PFS) of 8.1 months. For the whole cohort, median overall survival was 5.6 months (IC95%: 3.1-8.2) and PFS was 2.0 months (IC95%: 1.8-2.3). Conclusions: Our results suggest that metformin may have antitumor activity when combined with 5-FU/LV in a subgroup of mCRC pts, with acceptable toxicity. It is unlikely that 5-FU alone had activity in these heavily treated pts. Clinical trial information: NCT01941953.
A phase II study of panitumumab plus irinotecan for metastatic colorectal cancer with wild KRAS, resistant to fluoropyrimidine, oxaliplatin, and irinotecan in Japanese (OGSG1001).
Authors: Taira Koichi , Yoshida Motoki , Sugimoto Naotoshi , Kii Takayuki , Kuwakado Shin , Fukunaga Mutsumi , Hasegawa Hiroko , Kato Takeshi , Miyake Yasuhiro , Hata Taishi , Tokunaga Yukihiko , Takeda Koji , Daga Haruko , Yoshinami Tetsuhiro , Shimokawa Toshio , Sakai Daisuke , Kurokawa Yukinori , Satoh Taroh , Tsujinaka Toshimasa , Furukawa Hiroshi
Published: February 2017

607

Background: Anti-epidermal growth factor receptor (EGFR) antibody therapy showed to be effective in treatment for metastatic colorectal cancer (mCRC) with wild KRAS. Especially, combination chemotherapy with anti-EGFR antibody plus irinotecan is expected more effective than anti-EGFR antibody alone, resistant to irinotecan. We conducted a phase II trial of panitumumab plus irinotecan for mCRC with wild KRAS resistant to fluoropyrimidine, oxaliplatin, and irinotecan in Japanese. Methods: Subjects were mCRC patients with wild KRAS, who showed resistance to fluoropyrimidine, oxaliplatin, and irinotecan and had measurable disease, ECOG PS 0-2. Panitumumab (6 mg/kg) plus irinotecan (same dose as prior irinotecan) was administered every two weeks. This treatment was provided until progression. The primary endpoint was response rate (RR). Secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), response duration, and adverse event (AE). Results: A total of 31 subjects were enrolled between July 2010 and July 2012. Median age was 64 years old (range 42-74). Nineteen patients had liver metastasis, 11 had lung metastasis, and 3 had lymph node metastasis. An independent review committee evaluated for efficacy in eligible 31 subjects in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The RR of primary endpoint was 29.0% (95% confidence interval (CI), 14.2-48.0 %). DCR was 74.2% (95%CI, 55.4-88.1%) and median PFS was 5.6 months.(95%CI: 3.4-8.7) In 31 subjects for safety evaluation, the incidence of any Grade 3 or greater adverse events was 58.1%. Major adverse events of grade 3 were diarrhea (19.4%), rash acneiform (12.9%), fatigue (9.7%), anorexia (9.7%). A sudden death and an infusion related reaction were occurred. Conclusions: Combination chemotherapy with panitumumab plus irinotecan was demonstarated to be safe and more effective than Japanese single arm phase II of panitumumab alone for mCRC, resistant to fluoropyrimidine, oxaliplatin and irinotecan. This result in Japanese is equal to other reports of panitumumab plus irinotecan. Clinical trial information: UMIN000003819.
Morbidity and mortality after colorectal cancer surgery in patients with cirrhosis: A critical review of the literature.
Authors: Boussaha Tarek , Cadranel Jean François , Smail Allaoua , Lison Hortensia , Garioud Armand , Carola Elisabeth , Dumont Sarah Naomie , Chibaudel Benoist , André Thierry , Parc Yann
Published: February 2017

608

Background: Cirrhotic patients with localized colorectal cancer are potential candidates for tumor resection. The aim of this review was to evaluate the morbi-mortality after colorectal surgery. Methods: Comprehensive search was conducted using PUBMED, EMBASE, and the COCHRANE Library. Prospective and retrospective studies were selected. The study population included cirrhotic patients who underwent colorectal resection for non-metastatic colorectal cancer and patients with benign and other malignant disease. The postoperative morbi-mortality and independent risk factors were analysed. Results: Eight studies were identified. Among these, four studies compared the risk of colorectal surgery in patients with and without liver cirrhosis. The number of patients varied from 41 to 6,120. The severity of cirrhosis in most of the studies was classified with the Child-Pugh score. Class B and C were observed in 20% to 60% of the patients. Sepsis represented the main postoperative complication and occurred in 48% to 77% of patients. Mortality varied according to the Child-Pugh score, ranging from 11% to 41%, and was significantly higher for patients with cirrhosis in Child-Pugh Class C. Urgent surgical procedure had a negative impact on prognosis. The average length of hospital stay ranged from 9 to 18 days. Cirrhosis was associated with a 2-3 time and a 4-10 time increased risk of postoperative mortality in the absence and presence of portal hypertension, respectively compared with non-cirrhotic patients. The independent risk factors for postoperative morbidity and mortality were encephalopathy, ascites, low haemoglobin, prolonged prothrombin time, elevated bilirubin, hypoalbuminemia, postoperative infection, total colectomy, elective or non-elective surgery, the presence of co-morbidities and MELD score ≥ 15. Conclusions: Colorectal cancer surgery is associated with an increased risk of postoperative morbidity and mortality in cirrhosis patients. Studies evaluating exclusively the operative risk for colorectal cancer surgery in this patient’s population are rare. Prospective controlled trials to optimize the perioperative management of those patients are needed.
Pelvic side wall nodes in locally advanced rectal cancer as a prognostic indicator.
Authors: Laws Kirsten Elizabeth Jean , Wilson Christina , Harrow Stephen
Published: February 2017

613

Background: Neoadjuvant long course chemoradiotherapy is a well recognised treatment in locally advanced rectal cancer. Patients with pelvic side wall nodes are often considered for neoadjuvant treatment. We investigated whether pelvic side wall nodes identified on pre-treatment imaging is a poor prognostic factor and whether there are different patterns of recurrence compared to patients without pelvic side wall node involvement. Methods: All patients treated with long course chemoradiotherapy between January 2008 and December 2009 were identified. Patients were excluded if treatment indication was for inoperable disease, postoperative, recurrence, or palliative intent. 231 patients were identified and a retrospective analysis performed investigating patterns of recurrence and survival for patients with pelvic side wall nodes identified on pre-treatment imaging. Results: Kaplan Meier curves are presented showing patients with pelvic side wall nodes identified on pre-treatment imaging appear to have poorer outcomes and overall survival compared with those with only mesorectal nodes or no nodes. Patterns of recurrence are presented, showing patients with pelvic side wall nodes identified on pre-treatment imaging have a non significant trend to increased rates of disease recurrence (local and distal recurrence combined, 45.7% versus 27.9% for pelvic side wall nodes versus no pelvic side wall nodes). Patients with pelvic side wall nodes identified on pre-treatment imaging appear to be more likely to develop distant metastases compared to those patients who have mesorectal nodes or no nodal involvement (37% versus 23%). Conclusions: Our study highlights that patients with pelvic side wall nodes identified on pre-treatment imaging appear to have a trend to poorer overall survival, are more likely to recur and develop distant metastases. These results were not statistically significant, due to the small number of patients, and the data is consequently limited. We intend to further investigate current management strategies for this subgroup of patients, with assessment of radiotherapy treatment plans, current use of integral boosts, and surgical procedures for this subgroup of patients.
Comparative analysis of the effectiveness of second-line bevacizumab plus chemotherapy in second-line therapy in metastatic colorectal cancer.
Authors: Smagulova Kaldigul
Published: February 2017

619

Background: Advances in molecular biology and a wide introduction to the practice of targeted therapies have improved outcomes and significantly affect the overall survival of patients. To investigate the efficacy and safety of bevacizumab (BEV) beyond first progression combined with chemotherapy (CT) in patients with metastatic colorectal cancer. Methods: 68 patients with mCRC who received chemotherapy treatment at the Department of the Kazakh Research Institute of Oncology and Radiology. Selecting second-line chemotherapy based on oxaliplatin or irinotecan depended of an earlier first-line therapy (FOLFOX, FOLFIRI). The survival rate was calculated by Kaplan-Meier, comparison of survival curves was performed by log-rank. Results: The study included 68 patients, who were randomized from February 2009 to November 2011(to 33 [48.5%] BEV + CT and 35 [51.5%] to CT alone). Analysis of the immediate results of treatment showed that in neither case was not achieved complete response of the tumor. Partial regression in group 1 – 11 (33.3 ± 8.2)%, and group 2 - in 9 (25.7 ± 7.3)%. Stabilization is achieved in 20 (60.6 ± 8.5)% and 23 (6.7 ± 8.0)% of cases, respectively. The progression of the disease was observed in the group 1 in 2 (6.1 ± 4.1)% and 3 (8.6 ± 4.7)% of cases. Median progression-free survival (PFS) and overall survival (OS) was 11.5 months (7-16) and 12.2 months in group 1, and 9.7 months (6-13.2) (PFS), 9.1 months(OS) in group 2, respectively. The adverse event profile was consistent with previously reported data for BEV + CT. BEV-related significant adverse events included bleeding grade 3-4 (1.5 %) and venous thrombosis (2.3 %). Conclusions: Our findings demonstrate that BEV + CT continued beyond progression significantly prolong OS and PFS in second-line therapy mCRC.
The impact of treatment intent on overall survival after radiofrequency ablation of colorectal cancer liver metastases: The Royal Marsden Hospital experience.
Authors: Khan Khurum Hayat , Wale Anita , McCall James , Wijesekera Nevin , Khan Nasir , Chau Ian , Brown Gina
Published: February 2017

622

Background: 50% of patients with colorectal cancer will develop liver metastases (CLM), for many patients this will be the first and only site of metastatic disease. A minority of the patients will undergo surgical resection with curative intent, the remainder may be offered treatment with chemotherapy and local ablative techniques. Radiofrequency ablation (RFA) is increasingly used to treat patients deemed unsuitable for surgery, as an adjunct to or holding procedure before hepatic resection or for patients with recurrent disease. In addition some centres use RFA in the palliative setting. The aim of this study was to determine survival outcomes according to RFA treatment intent in patients with CLM. Methods: Clinical characteristics and survival outcomes of all patients with CLM treated with RFA between 2005-2011 were recorded. Patients were grouped according to the intent with which they underwent their first RFA procedure, namely "curative intent", "holding intent" or "palliative intent". Overall survival was compared between the groups using Kaplan-Meier survival analysis and Log Rank testing. Results: A total of seventy eight pts with CLM (M:F= 44:34), age (median=66, range 43-65 years), who underwent their first RFA procedure between 2005 and 2011 were identified. Thirty pts underwent RFA as a curative procedure (38%), 18 (23%) as a “holding procedure” before hepatic resection and 30 (38%) as a palliative procedure. The median OS for all patients was 25 months after first RFA treatment. Log Rank test showed survival was significantly different according to treatment intent; patients who underwent RFA as a holding procedure before hepatic resection had improved survival over those who underwent RFA with curative intent, who in turn had improved survival over those who underwent RFA with palliative intent (47 vs. 32 vs. 16 months, p = <0.001). Conclusions: Our study demonstrates that patients do best if RFA is used as neo-adjuvant treatment prior to hepatic resection, compared to when it is used as curative or palliative procedure. Careful selection of pts is required to optimise outcomes for the pts receiving RFA.
The impact of histologic tumor response on survival of patients treated with neoadjuvant mFOLFOX6 plus bevacizumab for the synchronous liver metastases from colorectal cancer.
Authors: Katayose Yu , Ishida Kazuyuki , Nakagawa Kei , Yamauchi Junichiro , Oikawa Masaya , Sakurai Naoki , Musha Hiroaki , Shimamura Hiromune , Miura Koh , Motoi Fuyuhiko , Egawa Shinichi , Unno Michiaki
Published: February 2017

625

Background: The synchronous liver metastases (SLM) from colorectal cancer (CRC) have a poor prognosis. Therefore, we conducted a phase II study of neoadjuvant mFOLFOX6 + bevacizumab for SLM to explore the appropriate initial treatment (BeFORE study). Here, assess the impact of histological tumor response (HR) on the relapse-free survival (RFS) and the overall survival (OS). Methods: The main inclusion criteria of BeFORE study were SLM within 10 nodules and with measurable disease. The primary endpoint was the response rate (RR). The secondary endpoints included R0-liver resection rate, HR, RFS and OS. Patients (pts) were enrolled after R0-resection of the primary CRC and received 8 courses of mFOLFOX6 + BV (the first and last courses were mFOLFOX6 alone). After this neoadjuvant chemotherapy, pts underwent resection of liver metastases within 4-8 weeks. HR was re-assessed on the basis of the tumor regression grade (TRG) which evaluates the extent of fibrosis of tumor cells, and the modified TRG which evaluates the extent of fibrosis and therapeutic-associated necrosis, using resected tumor samples. Results: Between June 2008 and November 2010, 47 pts were enrolled and 44 pts were treated per protocol. The median number of metastases was 2 nodules, and the maximum diameter of tumors was 12.9 cm. The overall RR was 72.7%. Forty pts underwent liver resection and 39 pts had the R0-liver resection. Five pts (12.5%) of resected 40 pts achieved TRG 1-2 (major HR), 5 pts (12.5%) had TRG 3 (partial HR) and 30 pts (75.0%) had TRG 4-5 (no HR). 8 pts (20.0%) achieved mTRG 1-2, 8 pts (20.0%) had mTRG 3, and 24 pts (60.0%) had mTRG 4-5. With a median follow-up of 35 months, the 2-year RFS rate was 27.3% (the median RFS was 10.5 months), and the 2-year OS rate was 88.4%. Here, we perform sub-group analyses of RFS and OS by TRG, mTRG, respectively. Conclusions: The impact of HR (TRG, mTRG) on survival could help us with considering about the appropriateness of neo-adjuvant mFOLFOX6 + BV as the initial treatment for SLM. (This trial is on University hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR); UMIN000001568.) Clinical trial information: UMIN000001568.
Survival by lymph node ratio (IG) in colorectal cancer patients in Oncologos del Occidente from Caldas: Colombia 1997–2012.
Authors: Villegas Mejia Carlos Raul , Rojas Gustavo , Chacon Cardona Jose Arnoby , Sanchez Villegas Tomas
Published: February 2017

641

Background: Colorectal cancer is the third cause of cancer death in the western world and in Colombia the fifth leading cause. The Caldas State being one of the five with the highest mortality rates. There are many prognostic factors reported in the literature but the clinical stage is the most important mainly determined by the number of involved nodes but exist other factors in their evaluation. It has been proposed Lymph Node Ratio (IG) ( Nro. (+) nodes / Nro. nodes removed x 100) for the analysis of nodal stage but there is controversy about its usefulness in various contexts. Methods: We made a descriptive study of patients with colorectal cancer attending at ONCOLOGOS DEL OCCIDENTE from Caldas - Colombia, who applied the Lymph node ratio (IG) and related to demographic, clinical and others prognostic factors in order to see its relation with overall survival at 5, 10 and 15 years. Results: 333 patients with 66% colon cancer, under 40 years 12% , women 50%, 68% without ACE data prior treatment, 41% on right colon, 49% medium rectum, 44% localized stage, 2% pathological complete response and 3% no classification data. Obstruction (29%), ulceration (25%) and 30% without prognostic factors, 33% had 12 or more lymph nodes removed, 50% N0 (TNM), 21% N2; the resected nodes, positive nodes, relapse, prior ACE and TNM as significant variables, 27% relapsed mainly liver, 50% had nodal index group 1 (0%); group 2 (1-20%) 15%, 14% group 3 (21-40%) and 21% group 4 (> 40%) . Mean follow-up: 53.7 months (SD: 43.8, Range:0 -218 months) and overall survival 64% at 5 years and 54% at 10 and 15 years. Conclusions: With an inadequate number of lymph nodes removed (33%) and multiple prognostic factors, Lymph node ratio is proposed like an independent prognostic factor in patients with colorectal cancer associated with overall survival at 5, 10 and 15 years, on which a therapeutic decision can be based.
Short-term outcomes of laparoscopic surgery after insertion of self-expandable metallic stent as a “bridge to surgery” for left-sided obstructive colorectal cancer.
Authors: Waki Yuhei , Tokuda Kazunori , Obatake Masayoshi , Nagahashi Miya , Hotchi Masanori , Kotegawa Hiroshi , Yoshiyama Hirotsugu , Harada Masamitsu , Kawasaki Hideki
Published: February 2017

643

Background: Safety and validity of performing laparoscopic surgery after preoperative lavege using the self-expandable metallic stent (SEMS) for left-sided obstructive colorectal cancer were examined. We evaluated the short-term outcome of SEMS insertion compared with laparoscopic surgery without SEMS. Methods: Patients with left-sided colorectal cancer treated by either laparoscopic surgery with stent placement (n = 8) or laparoscopic surgery only (n = 42) in our hospital between April, 2012 and January, 2013 were registered. Short-term outcomes were compared with the two groups about patient characteristics (sex, age, American Society of Anesthesiologists Physical Status, body mass index, prior abdominal surgery), pathological data of patients (tumor location, size of tumor , tumor differentiation, number of harvested lymph nodes, pTNM classification, UICC pathological stage), and operative and post operative results (procedures, conversion, operative time, blood loss, morbidity, solid food intake, postoperative hospital stay, total hospital stay). Results: Except for tumor size in the patient characteristic parameters, there were no statistically significant difference between the two groups. Conversion rate to laparotomy was higher in the stent group (2 versus 1, p = 0.013). There was no difference in operation time, blood loss and postoperative complications between the two groups. Conclusions: Although the long-term oncological result requires further investigation, laparoscopic surgery after self-expandable metallic stent is a safe and feasible treatment as a “brige to surgery” for left-sided obstructive colorectal cancer.
Influence of the localization of the primary tumor in the survival of patients with metastatic colon-rectal cancer treated with bevacizumab.
Authors: Gallego Jimenez Inmaculada , Lopez Ladron Amelia , Morales Pancorbo David , Fernandez Parra Eva , Rodriguez de la Borbolla Maria , Fuentes Pradera Jose , Bernabe Caro Reyes , Salvador Bofill Javier
Published: February 2017

665

Background: Bevacizumab, a humanized antibody against the molecular target endotelial growth factor VEGF-A, has incorporated to the standard of care of metastatic colon-rectal cancer (mCRC). A recent study has suggested that the left colon localization of the primary tumor may be a factor associated with a poorer survival in individuals treated against mCRC with bevacizumab including chemotherapy. Our objective was to analyze the impact of the localization of the primary tumor on the survival of patients with mCRC treated with bevacizumab. Methods: Prospective cohort study conducted in a tertiary-care hospital in Spain. Twenty-nine consecutive patients with mCRC who started a first-line therapy including bevacizumab were included. Patients were followed up until death, lost to follow-up or the censoring date (31th August, 2013). The primary end-point of the study was death from any cause. Predictors of survival, including the localization of the primary tumor, were assessed. Results: The median (Q1-Q3) age was 59 (52-67) years and 13 (45%) patients were male. Chemotherapy scheme was XELOX in 13 (45%) patients, FOLFOX in 8 (28%), FOLFIRI in 5 (17%), XELIRI in 2 (7%) and capecitabine in 1 (3%) patient. The localization of the primary tumor were distributed as follows: rectum in 6 (21%), sigmoid colon in 9 (31%), left colon in 9 (31%) and right colon in 5 (17%) patients. After a median (Q1-Q3) follow-up of 29 (13-41) months, 19 (66%) patients died. There were no patients lost to the follow-up. The mean (SD) survival in patients with left colon cancer was 25 (8) months whereas it was 47 (7) months in the remaining population (p = 0.1). The low sample size precluded to perform reliable multivariate analyses. Conclusions: Our study suggests that left colon localization of the primary tumor may have a worse prognosis in patients with mCRC treated with bevacizumab. Although no statistically significant differences have been observed, this fact may have been a consequence of the limited power of the analysed sample. Collaborative studies should be perfomed in order to clarify this issue.
The management of colorectal cancer (CRC) liver metastases with yttrium-90 microspheres (Y90): The south Australian (SA) experience.
Authors: Karapetis Christos Stelios , Padman Sunita Jo-Anne , Beeke Carol , Padbury Robert , Kitchener Michael , Kirkwood Ian , Voyvodic Frank , Ayres Oliver , Price Timothy Jay
Published: February 2017

666

Background: Treatment of CRC liver metastases with Y90 may provide a survival benefit but remains under investigation. We report on the accumulated SA clinical experience of using Y90 in the treatment of patients with metastatic CRC. Methods: Data from the SA mCRC Database was used to analyse the baseline characteristics of patients treated with Y90 to determine patterns of care. Safety and adverse outcomes, tumour response, disease progression, and survival were also examined. Survival outcomes were analysed using Kaplan Meier estimates, and chi square testing used for comparisons. Results: 33 patients received Y90, with median age 67 (range 33-83), 25 male, 29 colon/4 rectal primary, 25 hepatic only metastatic disease. Systemic therapy pre Y90 was as follows; nil=4, 1 line=7, 2 lines=9, ≥3=11, unknown=2. There were no immediate Grade III/IV adverse events, though immediate toxicity occurred in 9 patients; liver capsule pain in 8, chest pain and vomiting in 1 patient. Following Y90 treatment, radiologist reported response showed: measurable reduction =3 (ORR 9%), SD=4, PD=20, and 1 patient unknown. Treatment beyond Y90; nil=16 patients, 1 line=7, 2 lines=7 and >3=2 patients. Data on hepatic progression free survival (PFS) and overall PFS is currently being analysed. Median survival from the time of Y90 treatment was 10.3 months. Conclusions: Our data show Y90 use in SA occurs most often after 2 lines of chemotherapy. No immediate grade 3/4 toxicity was encountered. Survival for this select group appears longer than expected. Data on mOS from delivery of Y90, hepatic PFS and overall PFS for subgroups will be reported.
Evaluation of the frequency of c-Met and HER2 expressions in gastric carcinoma and their association with clinicopathologic factors.
Authors: Yalcin Suayib , Yildiz Yetkin , Sokmensuer Cenk
Published: February 2017

72

Background: Met and HER-2 protoonkogenes encode a receptor tyrosin kinase c-Met and HER-2. We aimed to determine the frequency of c-Met and HER-2 overexpression in gastric cancer and investigated their association with clinicopathological factors. Methods: Patients withstage I-IV disease were analyzed. Overexpressions of c-Met and HER-2 were determined with immunohistochemistry. Results: A total of 143 patients, 97 male 46 female were enrolled. C-Met score was 3 (+) in 31.5 %, 2 (+) in 27.3% and 1 (+) in 10.5% of the patients. There was no statistically significant differences in age, sex, tumor location, differentiation, Lauren classification, TNM staging, presence of distant metastasis, depth of tumor invasion (T), lymphovascular invasion, and survival between c-Met subgroups. HER-2 was 3(+) in 9.1%, 2(+) in 9.8%, and 1(+) in 16.1% of the patients. HER-2 overexpression was associated with better differentiation, intestinal subtype and advanced stage. C-Met overexpression was 84.6% in HER-2 3(+), 64.3% in HER-2 2(+), 69.6%, HER-2 1 (+) and 51.6% in HER-2 (-) patients. There was no statistically significant difference in survival between the c-Met overexpression positive and negative Stage III and IV patients. The median survival was 11.6 ± 6.3 months in HER-2 overexpression positive Stage IV patients and 11.9±6.8 months in HER-2 overexpression negative stage IV patients. There were no statistically significant differences in survival between the two groups. Conclusions: There is an association between c-Met positivity and HER-2 overexpression. C-Met was not associated with any negative prognostic factors in gastric cancer.
Risk factors and clinical outcomes of gastric cancer identified by screening endoscopy: A case-control study.
Authors: Jung Hwoon-Yong , Gong Eun-Jeong , Ahn Ji Yong , Lim Hyun , Choi Kwi-Sook , Lee Jeong Hoon , Kim Do Hoon , Choi Kee Don , Song Ho June , Lee Gin Hyug , Kim Jin-Ho , Choi Son Yeong , Choe Jaewon , Kim Min-Ju
Published: February 2017

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Background: A customized screening program for gastric cancer would optimize the benefits of screening endoscopy. This study investigated the risk factors for gastric cancer detected during screening, and factors affecting clinical outcomes. Methods: From April 2000 to December 2010, subjects who underwent screening endoscopy at Asan Medical Center were included. To investigate risk factors, age and sex-matched control group were selected.The clinical outcomes of gastric cancer identified during screening (screening group) were compared with age, sex and date of diagnosis-matched subjects who were diagnosed with gastric cancer in the outpatient clinic (outpatient group). Results: Of 109,530 subjects, 327 were diagnosed with gastric cancer. The median age of the screening group was 63.6 years (interquartile range: 56-71 years), and the male to female ratio was 2.4:1. When comparing with the control group, H. pylori seropositivity (odds ratio [OR] 2.933, p<0.001), carcinoembryonic antigen (OR 8.633, p=0.004), family history of gastric cancer (OR 2.254, p=0.007), and drinking (OR 3.312, p<0.001) were independent positive risk factors, and the use of aspirin a negative risk factor for gastric cancer (OR 0.445, p=0.012) in multivariate analysis. Low density lipoprotein cholesterol (hazard ratio [HR] 0.987, p=0.005), cancer antigen 19-9 (HR 21.713, p<0.001), resectability (HR 59.833, p<0.001), and family history (HR 0.308, p=0.009) were independent risk factors for death. The 5-year survival rate was significantly higher in the screening group than in the outpatient group (p<0.001). Conclusions: Early detection of gastric cancer by screening endoscopy while asymptomatic enhances patient outcomes, especially in high risk groups.
Randomized, multicenter, controlled evaluation of S-1 and oxaliplatin (SOX regimen) as neoadjuvant chemotherapy for advanced gastric cancer patients (RESONANCE trial).
Authors: Li Tao , Chen Lin
Published: February 2017

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Background: RESONANCE trial aims to improve 3-year disease-free survival (DFS) for patients treated with neoadjuvant chemotherapy and D2 surgery with chemotherapy postoperatively. We also evaluated the postoperative complications with and without preoperative chemotherapy to reveal the safety of SOX regimen. Methods: In this phase III multicenter study, patients with American Joint Committee on Cancer(AJCC,7thed)stage II-IIII advanced gastric cancer are treated with two to four cycles of preoperative SOX chemotherapy, followed by gastrectomy with D2 lymphadenectomy, and then another four to six postoperative cycles of SOX chemotherapy. Surgical and pathological quality control is performed. The primary endpoint is 3-year DFS, secondary endpoints are 3-year OS, D2/R0 rate, and toxicity and recurrence risk. The RESONANCE trial has been registered internationally, and twenty hospitals have participated in this trial. Results: Between February 2012 and to August 2013, 128 patients were enrolled in the neoadjuvant group , 103 patients were enrolled in the adjuvant group. Seventy-four of 128 patients underwent gastrectomy with D2 lymphadenectomy after preoperative chemotherapy. In these 74 patients, 52 (70%) patients had clinical tumor response and 10 (14%) patients achieved histological response. Operative mortality was never encountered. R0 resection rate was 90.5% after neoadjuvant chemotherapy compared with 94.2% in adjuvant group (p=0.23). Postoperative complication rates in neoadjuvant and adjuvant groups were 33.8% and 37.9% respectively (p=0.58). Conclusions: Results of this study will demonstrate whether neoadjuvant chemotherapy strategy will be superior to adjuvant chemotherapy when combined with D2 surgery for AJCC stage II-III gastric cancer patients. Furthermore, it might be an important clinical evidence to verify benefit of neoadjuvant chemotherapy in advanced gastric cancer. Clinical trial information: NCT01583361.
Prognostication in esophagogastric adenocarcinoma (OGA): Factors influencing overall survival (OS) in REAL3.
Authors: Waddell Tom Samuel , Chau Ian , Peckitt Clare , Patel Bijal , Gonzalez de Castro David , Wotherspoon Andrew , Middleton Gary William , Wadsley Jonathan , Ferry David , Mansoor Wasat , Crosby Tom David Lewis , Coxon Fareeda Y. , Smith David , Waters Justin S. , Iveson Timothy , Falk Stephen , Slater Sarah , Okines Alicia Frances Clare , Cunningham David
Published: February 2017

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Background: The REAL3 trial evaluated the addition of panitumumab (P) to epirubicin, oxaliplatin and capecitabine (EOC) in advanced OGA. We previously reported that addition of panitumumab was not associated with improvement in survival endpoints. In this analysis we aimed to explore factors associated with OS in the REAL3 population. Methods: Analysis performed in ITT population (n=553). OS was evaluated in relation to the baseline characteristics displayed in the table below. Cox regression was used to obtain HRs and 95% CIs. Factors with p<0.2 were included in a forward stepwise model and factors with p<0.1 were regarded as significant in the final model. OS was also assessed using the RMH Prognostic Index score which comprises 4 adverse variables: PS 2; liver mets; peritoneal mets; ALP >100 U/L. Results: Results of the univariate analysis are shown in the table below. In multi-variate analysis, the factors which remained statistically significant for OS were: PS (p=0.080): 1 vs 0 HR 1.24 (95% CI 0.99-1.57); 2 vs 0 HR 1.57 (95%CI 0.97-2.54) Disease extent (p=0.054): Met disease vs LA HR 1.42 (95% CI 0.99-2.02) Baseline global health score (p=0.005): Low vs high HR 1.52 (95% CI 1.16-2.00); middle vs high HR 1.45 (95% CI 1.11-1.89) Patients with an RMH Prognostic Index score of 0 (good prognosis) had median OS of 13.1 mo. This compared to 9.5 mo in patients with 1-2 adverse features (intermediate prognosis) (HR 1.37, 95% CI 1.12-1.68; p=0.002) and 4.7 mo in patients with 3-4 adverse features (poor prognosis) (HR 4.02, 95% CI 1.96-8.22; p<0.001). Conclusions: Baseline global quality of life may represent a useful adjunct to clinical parameters to guide prognostication in advanced OGA. These findings also validate the RMH Prognostic Index score in the REAL3 population. Clinical trial information: 2007-005976-15.[Table: see text]
Bone and soft tissue response from a phase I/II study with ODM-201 in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Garcia Jorge A. , Kataja Vesa V , James Nicholas David , Jones Robert Hugh , Protheroe Andrew , Massard Christophe , Mattila Leena , Mustonen Mika VJ , Aspegren John , Fizazi Karim
Published: February 2017

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Background: ODM-201 is a novel potent full androgen receptor (AR) inhibitor for CRPC. ODM-201 has excellent nonclinical efficacy in xenograft studies and high PSA response rate in CYP17i-naïve CRPC patients in the phase I/II ARADES study. Methods: To further analyze clinical efficacy of ODM-201 in CRPC pts we evaluated the overall response rate (ORR) in ARADES phase I/II study (Fizazi et al. Abstract #2853, ECC2013, Amsterdam 28 Sept 2013 ).Patients (pts) were enrolled into three dose levels 100mg bid, 200mg bid and 700mg bid. Results: All eligible 124 pts had progressive mCRPC; 37 pts were pre-chemo/CYP17i-naïve, 32 post-chemo/CYP17i-naïve and 55 post-CYP17i. Thirty-two (86%) pts in the pre-chemo/CYP17i-naïve group, 27 (84%) post-chemo/CYP17i-naïve and 48 (87%) post-CYP17i had bone disease at baseline. Similarly, twenty-two (29%) pts, 19 (59%) and 36 (65%), respectively had RECIST-define measurable disease. Median baseline PSA was 101ng/mL (3-1294) in pre-chemo/CYP17-i-naïve group, 94ng/mL (8-663) in post-chemo/CYP17-i-naïve group, and 139ng/mL (9-5000) in post-CYP17i group. CTC count was over 5CTCs per 7.5ml in 43% of the pts in pre-chemo/CYP17-i-naïve group, 41% in post-chemo/CYP17-i-naïve group and 44% in postCYP17i group. ORR data is presented in table below. Conclusions: Although RECIST-define responses were observed across the 3 different group of pts treated with ODM-201 the vast majority of pts had RECIST-defined SD up to 12 weeks. These data are in line with PSA data reported previously that demonstrate the clinical activity of ODM-201 in men with mCRPC. Clinical trial information: NCT01317641, NCT01429064. [Table: see text]
Anticancer activity of the selective CYP17A1 inhibitor, VT-464, in preclinical models of castrate-resistant prostate cancer.
Authors: Toren Paul , Pham Steven , Kim Soojin , Adomat Hans , Zoubeidi Amina , Moore William R , Gleave Martin Edwin
Published: February 2017

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Background: Castrate resistant prostate cancer (CRPC) continues to be sensitive to anti-androgen therapy as evidenced by the recent successes of abiraterone acetate (AA) and enzalutamide (ENZ). VT-464 is a novel, non-steroidal, small molecule CYP17A1 inhibitor with selectivity for the lyase activity of this dual enzyme. The objective of this study was to evaluate the anti-cancer activity of VT-464 compared to AA in CRPC in vitro models that are ENZ-responsive and ENZ-resistant and in an ENZ-resistant xenograft model. Methods: In vitro studies used the human CRPC, C4-2, and ENZ-resistant cell lines, MR49C and MR49F cells, in androgen-free media. AR transcriptional activity was assessed by probasin luciferase. AR-related and steroidogenesis pathways were assessed by western blot and/or qRT-PCR. A MR49F xenograft model in castrate mice compared oral VT-464 treatment to vehicle and AA. Steroid concentrations were measured using LC-MS chromatography. Results: VT-464 demonstrated a greater decrease in AR transactivation compared to AA in C4-2 and both ENZ-resistant cell lines. A greater decrease in AR-dependent gene transcription occurred with VT-464 treatment compared to AA in all cell lines. Prostate-specific antigen (PSA) protein levels in vitro were also lower with VT-464. Gene transcripts StAR, CYP17A1, HSD17B3 and SRD5A1 increased following treatment with VT-464 both in vitro and in vivo. A greater increase was seen with VT-464 treatment compared to AA. In vivo results demonstrated greater tumor growth inhibition and decreased serum PSA levels in mice treated with oral VT-464 compared to AA. Steroid analysis revealed lower testosterone (T) and dihydrotestosterone (DHT) concentrations in C4-2 cells with VT-464 treatment compared to AA. In vivo, the intra-tumoral DHT and T levels were significantly lower in response to VT-464 or AA compared to vehicle, with the greatest decrease seen with VT-464. Conclusions: The selective CYP17 inhibitor VT-464 demonstrated anti-cancer activity in pre-clinical models of CRPC, lowering intratumoral T and DHT concentrations significantly in castrate mice. These results suggest greater androgen suppression and inhibition of AR axis signaling by VT-464 than by AA.