bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of stage I/II colorectal cancer patients at risk of recurrence: The role of elastica stains to detect venous invasion.
Authors: Roxburgh Campbell SD , Foulis Alan K , Atwan Manal , Horgan Paul G , Mcmillan Donald C. 
Published: March 2020

e14117 Background: Venous invasion (VI) is a high-risk characteristic in colorectal cancer (CRC) and in stage II disease guides provision of adjuvant therapy. However, reported rates vary in published studies from 10-90%. We recently reported use of elastica stains improve reproducibility of reporting, increasing rates to >50% (Roxburgh, Ann Surg, 2010). Furthermore, compared to H&E alone, elastica detected VI provided superior prediction of 3yr cancer survival in an unselected cohort of CRC patients. The present study aims to examine how the approach could be used in patients with node negative CRC. Methods: We retrieved pre-2003 tumour blocks, sectioned and stained them with elastica. Post-2003, elastica detected VI was routinely reported. A minimum of 3 blocks was required for analysis. Those who died within 30 days of surgery or had neoadjuvant therapy were excluded. Results: 244 stage I/II patients underwent surgery between 1997-2006. 65 cases pre-2003 were analyzed retrospectively. The rate of elastica detected VI was 54%. Elastica detected VI related to other high-risk pathology including T stage (p<0.001), serosal invasion (p<0.01), tumour grade (p<0.05) and low-grade lymphocytic infiltrate (P<0.05). Minimum follow-up was 5 yrs; mean follow-up 99 months (60-178), during which there were 99 deaths, 48 from cancer. Absence of VI related to improved 5-yr cancer specific survival (93% vs 66%). On multivariate analysis, VI independently related to cancer specific survival (HR=5.5,95%CI 2-13,p<0.001) with margin involvement (HR=2.4,95%CI 1-6,p=0.067) and serosal involvement (HR=2.2,95%CI1-4, p=0.015). For CRC mortality, the area under the receiver operator curve was highest for VI compared with other pathology (AUC 0.69, 95%CI 0.6-0.8, P<0.001). Absence of VI related to 5-yr survivals of 92% and 97% in colon and rectal cancer respectively. Conclusions: More objective assessment of VI with routine elastica staining provides accurate prediction of survival in stage I/II CRC. Presence of VI was associated with a 5.5 fold increased risk of cancer death at 5 yrs. Such results support routine use of elastica stains to identify patients with node negative disease at risk of recurrence.
A dose escalation study of nimotuzumab plus irinotecan as second-line treatment in metastatic colorectal cancer with wild-type K-ras.
Authors: Zhou Jun , Shen Lin , Gao Jing 
Published: March 2020

e14122 Background: Nimotuzumab is a humanized monoclonal antibody of EGFR. We assessed the safety/tolerability and the efficacy of nimotuzumab combined with Irinotecan as the second-line treatment in Chinese patients with metastatic colorectal cancer (mCRC). Methods: Patients with mCRC refractory to oxaliplatin, K-ras WT, signed informed consent, target lesion(s), performance status (PS) ≤2, adequate organ functions, were eligible for this open-labelled, single-armed trial (NCT00972465). Irinotecan was given as 180mg/m2 d1, Q2w until progression or AEs or maximum 6 cycles. Nimotzumab was given as 200, 400, 600 or 800mg weekly until progression or AEs. The primary end points were objective response rate and toxicity. The second end points are PFS and OS. Results: A total of 31 patients (M/F = 22/9; median age 55; range 29-77) have been enrolled from July 2009 to Nov 2011. 4/11/12/4 patients received nimotuzumab as the dose of 200/400/600/800mg respectively. Most common grade 3/4 toxicity are leukopenia (14.8%,) and neutrocytopenia 18.5%). For all the patients, no grade 3/4 toxicity relating with Nimotuzumab was observed. 2 and 3 patients developed skin rash (grade 1) in 400 and 600mg arm respectively. 2 patients developed skin rash grade 2 in 600/800mg arm. The maximum tolerated dose has not yet been reached. Three patients (400/600mg: 2/1) quitted the trial because of personal reason. In 600mg arm, PR was 33.3% (4/12), SD was 25% (3/12); in 400mg arm, PR was 9.l%(1/11), SD was 36.4%(4/11); in 200mg arm, SD was 50%(2/4), PD was 50% (2/4); in 800mg arm, PR was 25%(1/4), PD was 75%(3/4). The follow-up of overall survival is ongoing. Conclusions: Addition of Nimotuzumab with 600mg weekly plus Irinotecan is safe and first data suggest a promising activity. The maximum tolerated dose of Nimotuzumab has not been reached yet.
FOLFIRI plus bevacizumab (B) as neoadjuvant treatment for potentially resectable colorectal cancer patients (pts) with liver metastasis: A phase II trial.
Authors: Nasti Guglielmo , Ottaiano Alessandro , Romano Carmen , Izzo Francesco , Delrio Paolo , Albino Vittorio , Giordano Pasqualina , Piccirillo Maria Carmela , Daniele Gennaro , Lastoria Secondino , Caraco Corradina , Arrichiello Cecilia , De Lutio Elisabetta , Maiolino Piera , Tatangelo Fabiana , Iaffaioli Rosario Vincenzo 
Published: March 2020

e14130 Background: Irinotecan-based chemotherapy plus B was shown to be effective and safe in both first- and second-line treatment for metastatic colorectal cancer (mCRC) pts.We designed this trial to assess whether the combination of FOLFIRI + B given to untreated, potentially resectable mCRC pts was feasible and active. Methods: Phase II, single arm trial with 1-year progression-free rate (PFR) as primary end-point. A sample size of 39 pts was calculated to detect a 70% ± 12% 1-year PFR. The treatment was FOLFIRI q2w (irinotecan 180 mg/m2, leucovorin 200 mg/m2, 5FU 2400 mg/m2 iv in 46 hrs) plus B 5mg/kg q2w. Last cycle before surgery was without B. Potentially resectable, untreated mCRC pts, with liver as unique site of metastases, were eligible. Normal organ function and no contraindications to B were required. Pts were reevaluated for surgery after 6 cycles. PET-Scan were performed at baseline and at the second cycle. Results: Overall 39 pts were enrolled. Median age was 58 (range 30-75), male/female were 24/15. Twenty seven pts (69.2%; 95%CI 52.4% – 83.0%) were progression-free at 1-year. Thirty seven pts (94.9%) underwent surgery. One complete and 22 partial responses were observed (response rate 59.0%; 95% CI 42.1% – 74.4%); 5 pts had disease progression (4 resectable and 1 unresectable). Early PET-scan was assessed according PERCIST criteria [Wahl RL, J Nucl Med 2009] in 29 pts and showed metabolic response (SUV-max decrease > 30%) in 17 (58.6%; 95% CI: 38.9%- 76.5%).Severe toxicity includes grade 3 neutropenia (3 pts, 7.7%) and grade 3 diarrhea (1 pt, 2.6%). Other toxicities include grade 1-2 diarrhea (15.4%), grade 2 nausea (7.8%), grade 2 leucopenia (5.1%), grade 2 asthenia (5.1%), grade 1 anemia (2.6%), grade 2 thrombosis (2.6%). Overall, 16 pts out of 37 experienced surgical complications (43.2%; 95%CI 27.1% - 60.5%): biliary leak (11 pts, 29.7%), biliary fistula (1 pt, 2.7%), other complications (4 pts, 10.8%). All complications were reversible. No peri-operative bleeding was observed. Conclusions: The trial yielded its primary aim and shows that FOLFIRI plus B is feasible and active as neo-adjuvant treatment in patients with resectable liver metastases of CRC.
Identification of clinical predictive factors of oxaliplatin-induced chronic peripheral neuropathy in colorectal cancer patients treated with adjuvant FOLFOX IV.
Authors: Frezza Anna Maria , Schiavon Gaia , Vincenzi Bruno , Addeo Raffaele , Catalano Vincenzo , Graziano Francesco , Santini Daniele , Tonini Giuseppe 
Published: March 2020

e14135 Background: Oxaliplatin-induced neuropathy is a dose-related side effect which occurs in almost 40% of patients treated with oxaliplatin. Aim of the present study was to identify reliable clinical factors predicting its development and duration. Methods: 169 completely resected CRC patients treated with adjuvant Folfox IV regimen were retrospectively included. The following pre-treatment clinical parameters were collected: hypocalcemia, hypomagnesaemia, hypoalbuminemia, anaemia, diabetes, chronic renal failure (CRF), folate deficiency, B12 deficiency, number of cycles received and habit to alcohol consumption. Incidence, grade (NCI-CTCAE v.3) and duration of neuropathy were recorded. Results: Incidence of neuropathy was found to be higher in patients with pretreatment anaemia (p=0.001), hypoalbuminemia (p=0.01) and hypomagnesemia (p=0.001) as well in those with habit to alcohol consumption (p=0.003). Neuropathy durations was conversely associated with age, being longer in younger patients (p=0.03), and again with hypoalbuminemia (p=0.04) and hypomagnesemia (p=0.002). No correlation was found with gender, hypocalcemia, diabetes and CRF. The correlation between vitamin B12 and folate levels and the development of neurotoxicity was not analysed because of the high number of missing data in the population. Conclusions: Age, anaemia, hypoalbuminemia, hypomagnesemia and alcohol consumption are reliable and easily assessable clinical factors predicting incidence and length of oxaliplatin induced neuropathy.
Year-to-year impact budget analysis of biologic therapies for first-line metastatic colorectal cancer (mCRC) therapy in Spain.
Authors: Martinez-Amores Brezo , Mezquita Laura , Ibañez de Cáceres Inmaculada , Ayuso Sacido Angel , Peña Jose Maria , Perona Rosario , Belda-Iniesta Cristobal 
Published: March 2020

e14144 Background: Pharmacoeconomic studies deal with populations of patients as if they were admitted at the division of medical oncology in the same date. Real patients are treated along the entire year so that budget simulations should be adjusted to chronological patterns of oncological assistance. Deferred budget impact analysis is undergone in order to assess long-run economic implications of clinical decisions on first-line mCRC therapies in Spain. Methods: As metastatic colorectal cancer diagnosis is not affected by seasonal influences, we have created a mathematical model assuming that a single patient is diagnosed every month and this patient has a 53% possibility to harbor a native K-Ras sequence. Calculi were arranged based on median duration of therapy. For bevacizumab-based therapy, budget impact for year t+1 begins at month 5 and beyond. For patients that receive cetuximab-based therapy, budget impact for year t+1 begins at month 7. The same approach was performed for doublets without any monoclonal antibody. Prices for all drugs in Spain were assumed to represent the best-value for each drug including all possibilities to reduce pharmacy costs. For first line, median duration of therapy reported by randomized trials was used to calculate the final budget. 70kg and 1.7 m were used as reference for patient dose calculations. Results: When K-Ras status is not tested and bevacizumab-based schedules are administered to every patient, annual growth of budget increases by 55- 60%. If K-Ras status is analyzed and wild-type patients are treated with cetuximab combinations and mutated patients receive bevacizumab, yearly budget growth amounts to 39-41%. Annual budget growth is minimized (25%) when K-Ras wt patients are treated with cetuximab combinations whereas K-Ras mutated tumours received chemotherapy alone. Conclusions: Duration of therapy plays a key role on budget impact estimations from both overall and year to year perspectives. K-Ras based clinical decisions not only optimize outcomes as measured by response rates but also minimize economic implications on annual budget growths.
A phase II study of perioperative FOLFOX4 plus bevacizumab for initially unresectable advanced colorectal cancer (NAVIGATE-CRC-01): Report of interim analysis.
Authors: Suenaga Mitsukuni , Mizunuma Nobuyuki , Fujimoto Yoshiya , Ueno Masashi , Matsusaka Satoshi , Shinozaki Eiji , Fukunaga Yosuke , Nagayama Satoshi , Yamaguchi Toshiharu 
Published: March 2020

e14145 Background: Perioperative chemotherapy combined with surgery for liver metastases is regarded as active strategy in metastatic colorectal cancer (mCRC). However, its impact on initially unresectable or potentially resectable previously untreated advanced CRC (ACRC), regardless of concurrent metastases, remains to be clarified. Methods: A phase II study to evaluate safety and efficacy of perioperative FOLFOX4 plus bevacizumab (BEV) for initially unresectable ACRC was conducted at a single institute in Japan. Previously untreated advanced colon or rectal (Rs-Ra) cancer and initially considered as unresectable ACRC (TNM: Stage IIIb, IIIc or IV) indicating potentially resectable after neoadjuvant chemotherapy (NAC) were eligible for this study. All patients provided their written informed consent. Patients received neoadjuvant FOLFOX4 plus BEV for six cycles. The sixth cycle did not include BEV. Duration between the last administration of BEV and surgery needed at least five weeks. Adjuvant FOLFOX4 plus BEV for six cycles were given after surgery. Completion rate of NAC and possibility of curative surgery were primary end point. Interim analysis of completion rate of NAC was planned at the end of NAC in the twelfth patient. Results: Characteristics of patients were as follows: gender, 8 male and 4 female: location, Sigmoid in 3, Ascending in 1 and Ra in 8: Stage, III in 8 and IV in 4 (liver or lymph node). All patients completed six cycles of NAC. No tumor-related severe adverse events or death were observed. Median duration between last administration of BEV, FOLFOX4 and surgery were 51 days and 34 days, respectively. Objective response to NAC was achieved in nine patients (75%), and no disease progression was observed. Eleven patients underwent curative tumor resection including metastatic lesion. Conclusions: The interim analysis met primary end point and suggests that neoadjuvant FOLFOX4 plus BEV is well tolerated and promise high response rate leading to curative surgery. These data indicate potential survival benefits from perioperative addition of BEV to the FOLFOX4 for initially unresectable ACRC if concurrent metastatic lesion.
Panitumumab as a single agent in 269 metastatic colorectal cancer patients in the real practice: A post EMA approval study.
Authors: Grude Francoise , Ramée Jean François , Guivarch Laurent , Rochard Sophie , Dupuis Olivier , Grollier Chrystelle , Guerin-Meyer Veronique , Leynia Pierre , Porneuf Marc , Peguet Elodie , Boucher Eveline , Bertrand Claude , Deguiral Philippe , Derenne Laurent , Achour Nacredine , Person Bernadette , Lebot Marie-Annick , Riche Christian , Metges Jean Philippe , Douillard Jean Yves 
Published: March 2020

e14148 Background: Metastatic colorectal cancer (mCRC) management has been improved by targeted therapies. The evaluation of the use of panitumumab (PANI), after approval, in the real life is strategic to assess health politics. Clinical trials concern usually patients younger and with better health status. Little is known about elderly people (over 70 years old). The observatory of Cancer Bretagne - Pays de Loire is a network of private and public cancer centers. Methods: Patients with wild-type KRAS, EGFR-expressing, mCRC progressing after fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy , received PANI,6 mg/kg biweekly. Sex, age, primary tumor, line of treatment, toxicity, reason of discontinuation, response, progression free survival (PFS) and overall survival (OS) were collected. Results: 269 patients (183 men and 86 women) treated between second half of 2008 and end of 2010 have been included. Median age: 67 years [36-90] (Amado et al, 2008 : 62.5 years [29-82]). Primary tumor was : colon (74%), rectum (24%) and double site (2%). PANI was used mostly at line 2 (19%), 3 (31%) or 4 (29%). Discontinuation of treatment was due to disease progression: 53%, death: 12% and toxicities: 5% (skin toxicities 3.5%). Clinical response was evaluated for the first 201 patients: partial response (PR): 20%, stable disease (SD): 19% and progression (P): 60% (Amado et al, 2008 PR : 17%, SD : 34%, P : 49%). Median duration of treatment was 2.3 months [0.26-17.52]. Median of OS was 6.71 months which is lower than previously described (Amado : 8.1 months). Median duration between end of treatment and death when death is the cause of end of treatment was 17 days [4-57] (n=24). From our data of 269 patients, a comparison between 123 patients over 70 and 146 patients under 69 will be shown at the meeting. Conclusions: Analysis of patients treated with PANI for a mCRC allows assessing the proper, per label use, in the real life. Complete results on clinical response, PFS, OS and safety as well as previously published data will be shown at the meeting.
Renaissance of contact radiotherapy with RT 50 Papillon machine: A revival of new treatment option for early low rectal cancer?
Authors: Sun Myint Arthur ,   International Contact Radiotherapy Society
Published: March 2020

e14149 Background: Local contact radiotherapy for early rectal cancer is an accepted treatment in most centers but still controversial in some centres. However, the old Philips machine is obsolete and many centers are unable to continue treating patients using this technique. A new RT 50 Papillon machine is now commercially available and there is a new hope for elderly patients and others who whish to avoid major surgery or permanent stoma. Methods: Although contact radiotherapy has been in clinical use for the past 80 years it is still not regarded as standard treatment in many centers around the world. This is due to the fact that there were no large randomized trials to prove its efficacy against standard surgical treatment. ICONE group has launched CONTEM trials, which are observational trials that combine Contact RT with TEMS for various stages of malignant rectal polyps. Results: ICONE group meets annually and organized courses for contact radiotherapy. So far, 10 centers in Europe have now been trained. We hope to start the CONTEM trials later this year. The data from these trials will be collected centrally in Nice and updated annually. The results will be published later. Conclusions: At present approximately 30-50% of patients with early (T1N0) low rectal cancer (<6cm) are being over treated with APR. Revival of contact radiotherapy allows multimodality treatment for selected patients to avoid major surgery and permanent stoma. We hope the CONTEM trials will provide some evidence in this approach for suitable patients with early rectal cancer. [Table: see text]
Clinical significance and prognostic impact of CD133 expression in rectal cancer treated with preoperative radiochemotherapy.
Authors: Sprenger Thilo , Conradi Lena-Christin , Beissbarth Tim , Homayounfar Kia , Rüschoff Josef , Rödel Claus , Ghadimi B. Michael , Becker Heinz , Rödel Franz , Liersch Torsten 
Published: March 2020

e14161 Background: CD133 has been described as a potential stem cell marker in colorectal cancer and to be associated with higher tumorigenic potential and resistance to radiochemotherapy (RCT). In this study the expression of CD133 was evaluated in pre-RCT tumor biopsies and the corresponding post-RCT surgical specimens of locally advanced rectal cancer patients and correlated to histopathological features and clinical follow-up. Methods: 127 patients with UICC (Union contre le Cancer) II/III rectal cancer treated with preoperative 5-FU based RCT within the German Rectal Cancer Trials were investigated. Pre- and post-RCT CD133 expression levels were determined using immunhistochemistry and correlated with histopathologic parameters, tumor regression grade, cancer recurrence and survival. Results: As compared to pre-RCT biopsies we observed a significantly higher CD133 expression in tumor specimens (p=0.01). There was, however, no correlation for both biopsies and tumor specimens between CD133 expression levels, histopathological features and survival. In matched analyses of corresponding biopsy/tumor pairs, patients with a decreased fraction of CD133+ cells after preoperative RCT showed significantly lower residual tumor stages (p=0.03) and higher histopathological tumor regression (p<0.01). Moreover, these patients had a significantly improved disease-free (DFS) and cancer-specific overall survival (CSS) in uni- (p<0.001) and multivariate analyses (p=0.001), respective. Conclusions: Enrichment of CD133+ cancer cells during preoperative RCT is correlated with minor local tumor response, distant cancer recurrence and survival. Up-regulation of intratumoral CD133 expression – more than pre- and post-RCT CD133 levels – plays an important role in therapy resistance, tumor progression and metastasis in rectal cancers undergoing neoadjuvant RCT.
A qPCR gene expression module test to predict resistance to cetuximab in colorectal cancers independent of KRAS mutation status.
Authors: Rhodes Dan , Eddy Sean , Williams Paul , Tomilo Mark , Sadis Seth , Wyngaard Peter , Vo Lien , Oades Kahuku , Kim Hyunsoo , Wang Yipeng , Lee Byung-In , Monforte Joseph 
Published: March 2020

e14164 Background: While KRAS mutation predicts resistance to anti-EGFR therapy in colorectal cancer, not all KRAS wild-type patients benefit from such therapy, suggesting that complementary biomarkers capable of identifying additional non-responsive patients would have clinical utility. Methods: To search for such a biomarker, we studied the relationship of cetuximab response with twelve gene expression modules, derived from an unsupervised analysis of 20 independent microarray datasets comprising more than 2,000 colorectal cancer patients. Each module represents a set of highly co-expressed genes related to an important aspect of colorectal cancer variability. Two cetuximab-treated cohorts were studied. The first was a Phase II clinical trial (Khambata-Ford et al, J Clin Oncol, 2007) with accompanying microarray data from pre-treatment biopsies. The second was a single-institution study of cetuximab response from which formalin-fixed paraffin-embedded primary tumor specimens were available. Results: In the first study, module scores were computed by averaging co-expressed module genes in the microarray data. In the second study, module scores were generated from a qPCR gene expression module test, OncoScore Colon, which quantifies modules by averaging three representative module genes relative to housekeeping controls. Notably, in both studies, the mesenchymal module was significantly associated with cetuximab resistance, with module positive patients tending to progress on cetuximab within 10 weeks. Additionally, the status of this module was independent of KRAS mutation status—KRAS mutations occurred in both module-positive and -negative patients. Future clinical studies will continue to test the predictive capacity of the module in regards to cetuximab resistance and other mechanisms. Conclusions: In summary, this study demonstrates the value of a gene expression module-based qPCR panel for stratifying colorectal cancer patients for treatment response, and suggests that our approach may have immediate utility for cetuximab treatment response prediction.