bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fate of disappeared hepatic metastasis after mFOLFOX6 plus bevacizumab therapy.
Authors: Uetake Hiroyuki , Ishikawa Toshiaki , Sugihara Kenichi 
Published: March 2020

e14127 Background: Neoadjuvant and conversion chemotherapy for liver limited metastasis from colorectal cancer (CRC) is a current topic. Minute liver metastasis sometimes disappears on preoperative imaging and intraoperative examination (including contrast enhanced intraoperative ultrasonography (CEIOUS)) after chemotherapy using highly effective regimen, such as FOLFOX or FOLFIRI with molecular targeted agent. We reported a high pathological complete response (CR) rate of resected liver metastasis from CRC after preoperative mFOLFOX6 plus bevacizumab (Bmab) therapy (AACR 2011, abstract #3218), but It is still unclear whether disappeared lesions after chemotherapy need to be removed. Methods: Out of 17 patients with liver limited metastasis from CRC treated with mFOLFOX6 plus Bmab therapy, 9 patients (52%) underwent liver resection after chemotherapy. In 6 of the 9 patients, one or more disappeared lesion(s) after the chemotherapy was not resected and followed up by enhanced CT once every 3 months. Follow up period was 9 to 33 months (22 months in median). Results: Before chemotherapy, 53 liver metastases were detected in the 6 patients. After chemotherapy, 29 (55%) lesions were not detected by preoperative CT or CEIOUS. All the 24 lesion, which were pointed out at the operation, were resected. By histological examination, no viable tumor cell was observed in 12 lesions (50%) among resected lesions. In follow up period, in situ recurrence occurred in 5 lesions (17%) in 4 patients. Three of the 4 patients underwent curative resection of re-detected liver metastases. Conclusions: It was reported that cancer cells remain over 80% of clinically disappeared lesion after conventional chemotherapy. In the present study, only 17% of disappeared lesion after mFOLFOX6 plus Bmab therapy caused in situ recurrence. With this result and a high pathological CR rate of the resected liver metastases after mFOLFOX6 plus Bmab therapy, it is speculated that complete resection for disappeared lesions after this chemotherapy is not always necessary.
Changing prognosis of metastatic colorectal adenocarcinoma (mCRC) 1988-2008 within the general population: Has everyone benefitted?
Authors: Lawrence Yaacov Richard , Golan Talia , Aderka Dan , Shani Adi , Zach Leor , Ben-David Merav A. , Gluck Iris , Rabin Tatiana , Pfeffer Raphael M. , Catane Raphael , Berger Raanan , Symon Zvi 
Published: March 2020

e14143 Background: Between 1991 and 2008 the FDA approved 7 new drugs for the treatment of mCRC. The results of randomized phase III trials, performed on selected (e.g. younger) patient populations, may not reflect net benefit seen within the general population. We therefore performed a population-based survival analysis of patients who initially presented with mCRC. Methods: Survival statistics were extracted from the Survival, Epidemiology and End Results (SEER) Database for patients diagnosed with mCRC between 1988-2008. Survival was analyzed using the Kaplan-Meier method and proportional hazard models as appropriate. Exclusion criteria included diagnosis at autopsy, non-adenocarcinoma and unknown histology. Results: The study population consisted of 42,347 patients diagnosed with mCRC from 1988-2008, 52% female. Mean age 67 years; 46% were aged 70 or over. Prognostic variables included race, gender, age, marital status, disease site, surgical resection and year of diagnosis (for all p<0.001). For the entire population median OS improved from 8 months in 1988 to 14 months in 2007. Net improvement in OS was highly dependant upon age: for pts<50 yr OS improved from 9m to 21m; for pts 50-69 yr from 10m to 17m; for pts >=70 yr from 7 to 8m. Conclusions: There has been a continuous improvement in OS of patients diagnosed with mCRC between 1988 and 2008. We could not determine if this was due to new therapeutic agents or improved imaging leading to earlier diagnosis. Little improvement has been seen in patients >70 years age. The disparity in median OS between younger and older patients with mCRC over this period has widened from 2 months in 1988 to 13 months in 2008.
Cetuximab, capecitabine, oxaliplatin, and radiotherapy as preoperative triple treatment for rectal cancer (CET-CAPOX-RT-Phase-I/II Study): Influence on long-term survival and relevance of biomarkers.
Authors: Liersch Torsten , Conradi Lena-Christin , Sprenger Thilo , Middel Peter , Sülberg Heiko , Rödel Franz , Rüschoff Josef , Beissbarth Tim , Arnold Dirk , Rödel Claus 
Published: March 2020

e14162 Background: Preoperative application of cetuximab and radiochemotherapy combined with 5-FU+oxaliplatin (CET-CAPOX-RT-phase-I/II-study) failed to increase the complete remission rate (pCR, primary endpoint) in rectal cancers. Here, we report longterm survival in respect of biomarkers. Methods: In 45 of 53 patients (85%) total mesorectal excision (TME) was performed with curative intention. Disease-/progression-free survival (DFS/PFS) and overall cancer specific survival (CSS) were correlated with clinicopathological findings (e.g. tumor regression grading (TRG), KRAS-, HER-2-, Ki67-, EGFR-, IGF1R-, Src-, PTEN-, Survivin-, XIAP- and thymidylatesynthase(TS)-status). Results: After triple RCT, ypUICC stages were 0 (4x), I (17x), II (10x), III (14x) and IV (7x); RCT-induced T-level- (49%) and UICC-downcategorizing (53%) correlated with major (38% TRG 3-4) versus minor response (62.3% TRG 0-2) (p=0.005 and p=0.02, respectively). During follow-up (63 months) 7/53 patients with M1-status at surgery died. In 45 patients with M0-status no locoregional failure but in 5 patients metastatic recurrences were detected. DFS at 1, 3 and 5 years was 90.7% (CI: 82.5-99.8), 88.3% (CI: 79.2-98.5) and 88.3% (CI: 79.2-98.5); the CSS was 97.6% (CI: 93.1-100), 95.2% (CI: 89-100), and 90.3% (CI: 82-99.8), respectively. Patients with ypN0-status demonstrated better DFS (p=0.027), PFS (p=0.024) and CSS (p=0.016). KRAS mutations (33%) had no prognostic influence but a positive HER-2-status (18%) seemed to be associated with better CSS (p=0.11). High Ki-67-expression (p=0.09) as well as the loss of RCT-induced Survivin-downregulation (p=0.05) correlated with reduced CSS. No prognostic influence was found for EGFR-, IGF1R-, Src-, PTEN-, XIAP- and TS-expression. Conclusions: The disappointing pCR rate of the CET-CAPOX-RT-phase-I/II-study did not translate to poor longterm survival.
Early rise in blood pressure to predict clinical outcomes in metastatic colorectal cancer (mCRC) patients treated with first-line bevacizumab.
Authors: Upanal Nazeerahamad N. , Ackland Stephen P. , Bonaventura Antonino , McElduff Patrick 
Published: March 2020

e14166 Background: Bevacizumab (Bev) induced hypertension (HTN) may be a predictive biomarker of anti-tumor activity in patients with metastatic colorectal cancer (mCRC) . We retrospectively assessed if significant rise in blood pressure (SRBP) [ ≥ 20 mmHg ] or any grade of HTN within first 10 weeks of treatment with bev is associated with improved clinical outcomes. Methods: Retrospective review of all mCRC patients, on or off clinical trial, treated with first line chemotherapy plus Bev (5 mg/kg Q2W or 7.5 mg/kg Q3W) at our institution from 2005-2010 was conducted .BP was measured before each treatment and graded according to CTCAE version 3.0.The median follow-up time of eligible patients was 19.6 months. Results: Of 50 patients eligible for the analysis, 20 patients (40%) developed significant rise in BP or HTN (SRH) whereas 30 patients had no change (NRH). There were no statistical differences between the two groups with respect to age, gender, ECOG status, number of sites of metastases, pre-existing HTN (55% SRH,37% NRH ; P=0.251) and first line chemotherapy regimen. Chemotherapy regimens used in SRH and NRH groups were 5-Fluoropyrimidine based (25% vs 23.3%), irinotecan based (40% vs. 36.7%) and oxaliplatin based (35% vs 30%). Four patients (20%) in the SRH group developed SRBP and other patients in this group developed G1-G3 HTN according to CTCAE v3.0.SRH group had improved median progression free survival (15.8 vs 6.2 months ; p<0.001) and overall survival (25.9 vs. 16 months; p=0.005). Overall response rate was higher in the SRH group (75% vs 26.7%; p=0.001). Conclusions: SRH developing within 10 weeks of commencing first line chemotherapy with bev correlates with improved outcomes in mCRC. These data need confirmation in prospective studies.
The morbidity of cytoreduction/hyperthermic intraperitoneal chemoperfusion (HIPEC) in the modern era.
Authors: Haslinger Michelle , Kane John Michael , Francescutti Valerie , Burke Rachel , Skitzki Jospeh J. 
Published: March 2020

e14172 Background: Critics of cytoreduction/HIPEC for treatment of peritoneal surface malignancies cite high morbidity/mortality in historical published literature. With improved patient selection algorithms based upon recent clinical experience, perioperative morbidity/mortality should be comparable to the treatment of other GI malignancies. Methods: Retrospective data collection on all patients undergoing cytoreduction/HIPEC at a single institution (2 surgeons) from 2003-2011. Patient demographics, perioperative complications, mortality, and survival were analyzed (logistic regression modeling, Kaplan Meier, and Log rank testing). Results: 113 patients (45M/68F; median age 53 years) underwent 124 cytoreduction/HIPEC procedures. Primary tumor histology was colorectal adenocarcinoma (34%), appendiceal DPAM (24%), appendical adenocarcinoma (21%), mesothelioma (10%), and other (11%). 46% of patients received systemic chemotherapy prior to cytoreduction/HIPEC. Median HIPEC time was 12 hours (range 6 to 20 hours). All patients received mitomycin C at first HIPEC with 26% receiving a dose reduction. Median number of GI anastomoses was 1 (range 0-3). Median ICU stay was 1 day (range 0-21) and median length of stay (LOS) was 12 days (range 6-122). Major postoperative complications included wound infection (15%), anastomotic leak (11%), neutropenia (7%), pulmonary (5%), and thromboembolic events (2%). The reoperation rate for complications was 15%. Operative mortality at 30 and 60 days was 0% and 3%, respectively. As a surrogate for complications, LOS >14 days occurred in 24% of patients. Median follow-up was 25 months (1-80 months). Median progression-free and overall survival were 26.3 and 68.5 months, respectively. An anastomotic leak was associated with increased LOS, decreased progression-free survival (15.3 months, p< 0.05) and overall survival (15.3 months, p< 0.005). Conclusions: Despite being stage IV disease, perioperative morbidity/mortality for cytoreduction/HIPEC is comparable to surgical treatment of primary upper GI malignancies. Patient selection and meticulous technique may be critical to avoid anastomotic leaks associated with decreased survival.
Impact on overall survival and disease-free survival of adjuvant chemotherapy after neoadjuvant chemoradiotherapy for rectal cancer.
Authors: Castro Rafael amaral de , Paiva Carlos Eduardo , Saad-Hossne Rogerio , Michelin Odair Carlito , Souza Cristiano de padua 
Published: March 2020

e14173 Background: Colorectal cancer is the second most common cancer with 2,4 million people diagnosed. The rectal cancer (RC) is 27% of these cases. Neoadjuvant chemoradiotherapy (NCRT) has become standard but brought controversy in the adjuvant treatment. The objective was to assess the impact of adjuvant chemotherapy after NCRT. Methods: Between mar/96 and Oct/2010, 84 patients received NCRT, and 58 patients underwent resection of the rectum. The NCRT consisted of 5-FU 350mg/m2, D1-D5 (50% of cases) or 5-FU 425mg/m2, D1-D3 (43%) with LV 20mg/m2 bolus in the 1st and 5th week of the 25 sessions of radiotherapy in linear accelerator (total 45 - 50 Gy). When performed, Adjuvant chemotherapy (ADJC) consisted of 5-FU 425mg/m2, LV 20mg/m2, both on D1-D5 for 4 cycles. Evaluation of Overall Survival (O.S) and Disease-Free Survival (DFS) performed using Kaplan-Meier curve in SPSS version 13.0 Results: Of the 58 patients who underwent surgery, 90% were stage II, 51% occurred in the lower rectum and 66% were ECOG 1. Pathologic Complete Response (PCR) was obtained in 25.8% (15) of patients (group 1). Of these, 20% (3) received ADJC. Patients without PCR (group 2) received ADJC in 51% of the cases (22). The mean follow-up was 41 months. Both the DFS (HR: 2.594, 95% CI: 1134-5938, p = 0.024) and OS (HR: 2.615, 95% CI: 1005-6807, p = 0.0488) were higher in patients with PCR independent of the use of ADJC. On the other hand, patient treated with ADJC vs without ADJC, independent of presence of PCR, did not alter DFS (p = 0.74) or OS (p = 0.32). In PCR patients, ADJC do not interfere in the outcome (DFS, p = 0.76; SG, p = 0.73). In group 2 (patients without PCR), the subgroup with ADJC, there was a trend towards better SLD (p = 0.06) and OS (p = 0.06). Those who did not receive ADJC in group 2 had worse SLD (p = 0.011) and OS (p = 0.028) compared with group-1. Conclusions: Adjuvant treatment after NCRT did not increase OS or DFS. Patients without PRC had worse results without ADJC, compared to those with PCR. The first, probably, the subgroup of patients who benefited most from the use of ADJC. PCR improves OS and DFS regardless of ADJC, being perhaps the group that does not deserve ADJC.
Colorectal cancer screening barriers.
Authors: Patel Monaliben , Malin Jessica , Headly Anna 
Published: March 2020

e14175 Background: Colorectal cancer is the third cause of cancer death in the U.S., yet only 53% of adults over 50 are screened. Rates for minorities and patients without a high school education are lower. Colonoscopy may prevent 65% of cancers; identifying obstacles to screening could save lives. Our objective was to investigate obstacles and improve screening in Camden, NJ, a city that is 95% minority, only half of adults have completed high school, and 44% of families live below poverty level. Methods: In coordination with the American Cancer Society and Horizon Medicaid, we obtained data on Horizon enrollees at a primary care practice of Cooper University Hospital in Camden. All patients 50 and above with no insurance claims for screening in the last 10 years were included. 92 patients met criteria. We attempted to contact each by phone (via interpretation service if Spanish speaking). A standardized template was used to explain benefits of screening, ask for reasons for not having screening, offering transportation to the procedure, and asking if they were willing to have a colonoscopy. Patients who agreed were scheduled for colonoscopy. Results: 92 patients were identified. 30 could not be contacted after 3 attempts. Of 62 contacted, 12 agreed to colonoscopy; 25 stated they had already had screening; and 25 declined. Of 12 who agreed, reasons for not having had screening were: lack of awareness (6 patients, 5 Spanish speaking); not having transportation (3, 1 Spanish); and simply having put it off (3). Of 25 who declined, reasons were: desire to schedule themselves (8); the subject was too uncomfortable (4); mistrust of doctors (1); and being too scared (1). 10 (7 Spanish) gave no reason, and 1 had moved. Conclusions: Obstacles identified to colorectal screening were 1) lack of awareness (50% of patients who agreed to procedure); 2) transportation (25% of patients who agreed); 3) language barriers (83% of those who were unaware of recommendations were Spanish speaking); 4) fear/mistrust (8%); and 5) having lost contact with the system (33%). Efforts toward increasing screening should be targeted accordingly. We acknowledge the ACS and the Walmart Foundation for their participation and support. Findings and conclusions do not necessarily represent the views of ACS and the Walmart Foundation.
Clinical benefit rate (CBR) of panitumumab monotherapy among patients with KRAS wild-type metastatic colorectal cancer (mCRC).
Authors: Kennecke Hagen F. , Lim Howard John , Johal Balvindar Singh , Zulfiqar Muhammad , Speers Caroline 
Published: March 2020

e14176 Background: Panitumumab (Pmab) improves progression free survival as first-, second- and third-line therapy for KRAS wild-type (wt) metastatic colorectal cancer (mCRC). Only in the third-line setting is there evidence of benefit of Pmab monotherapy. In this analysis of an exploratory biomarker study of Pmab monotherapy, the clinical benefit rate of Pmab according to previous lines of therapy is described. Methods: Patients (pts) with KRAS non-mutated, measurable MCRC previously treated with or ineligible for oxaliplatin/5-FU and irinotecan were treated with Pmab 6mg/kg IV q2w until progression or toxicity. The primary endpoint is clinical benefit rate (complete (CR) or partial response (PR) + prolonged stable disease (PSD) > = 24 weeks) by RECIST criteria. Results: The study completed accrual and (40) evaluable patients were treated between September 2009 and December 2011 of which 32 were evaluable for the primary endpoint. Median follow-up was 8.8 months, median age was 64.5 years and 90% were ECOG 0/1. Previous therapy was: 5-FU/Capecitabine(C) only in 12 pts, Irinotecan/5-FU/C only in 2 patients, Oxaliplatin/5-FU/C only in 3 pts, Oxaliplatin/Irinotecan/5-FU/C in 23 pts. 22 patients received prior Bevacizumab. Median number of cycles was 8 and 6 pts required a dose modification. There were 7 (22%) PRs and 7 (22%) pts experienced PSD >=24 weeks. Clinical benefit rate (PR+PSD) according to previous therapy was 33% (3/9) for 5FU/C only, 100% (2/2) Oxaliplatin/FU/C only, 0% (0/2) Irinotecan/FU/C only, and 47% (9/19) for Oxaliplatin/Irinotecan/5FU/C. Conclusions: Pmab monotherapy is well tolerated and response rates vary according to previous lines of therapy. Patients ineligible for irinotecan and/or oxaliplatin experience a high clinical benefit rate with single agent Panitumumab and should be considered for such therapy. Updated study results will be presented.
Feasibility analysis of mutational status of advanced colorectal cancer patients and correlation to disease progression.
Authors: Grissom Daniel , Wade Mark , Weis John R. , Boucher Kenneth M. , Sharma Sunil 
Published: March 2020

e14177 Background: Mutational Analyses are being increasingly performed on colorectal cancer patients. More efforts are needed to correlate this data to clinical outcomes such as disease prognosis, metastasis, and tumor responsiveness to chemotherapy or targeted therapy. We assessed the mutational status of patients diagnosed with colorectal cancer in the GI oncology clinics of Huntsman Cancer Institute. Methods: We examined 46 patients diagnosed with colorectal cancer that had molecular profiling performed. To determine effectiveness of mutation analysis we compared the time to progression (TTP) of patients in correlation to KRAS or BRAF, PIK3CA and PTEN status. KRAS, BRAF and PIK3CA testing was performed by direct sequence analysis on genomic DNA isolated from a formalin-fixed paraffin-embedded tumor sample. Testing utilized custom primers designed to flank, amplify and sequence codons 12 and 13 in exon 2 and codon 61 in exon 3 of the KRAS gene, codons 464-469 of exon 11 and codon 600 of exon 15 in the BRAF gene located at 7q34, and codons 539-546 of exon 9 and codons 1043-1049 of exon 20 in the PIK3CA gene located at 3q26.3. PTEN expression was determined by immunohistochemistry. H-score of ≤10 was considered PTEN Low. Results: Of the patients reviewed there were 26 male, 20 female with a median age of 59 (23-81). 43 patients had metastatic disease and 3 patients had localized disease. Mutations found were 48% KRAS, 6% BRAF, 13% PIK3CA, 46% PTEN Low, 13% KRAS + PIK3CA, and 28% KRAS/BRAF + PTEN Low. In patients with KRAS/BRAF wild type (n=14), median TTP from diagnosis to starting first chemotherapy for metastatic disease was 365 days as compared to KRAS/BRAF mutant (n=21) of 182 days (p=0.008). This study could not detect any correlation between dual alterations in RAS with PI3 kinase pathway and TTP probably as a function of lower sample sizes. Conclusions: Our data supports association of KRAS and BRAF mutational status to TTP rates in colorectal cancer patients. Substantial numbers of patients have alterations in the PI3-Kinase pathway in combination with the RAS pathway. Continued testing of molecular mutational status is needed in order to improve these predictive models.
Clinical benefit of panitumumab after cetuximab failure in patients with metastatic colorectal cancer.
Authors: Haraldsdottir Sigurdis , Wu Christina Sing-Ying , Rose Jeffrey Scott 
Published: March 2020

e14178 Background: Panitumumab (Pmab) is a fully humanized monoclonal IgG-2 antibody against epidermal growth factor receptor (EGFR). It was approved by the FDA in September 2006 as 3rd line therapy in metastatic colorectal cancer with disease progression on or following fluoropyrimidine (5-FU), oxaliplatin, and irinotecan chemotherapy regimens. Cetuximab (Cmab) is a chimeric monoclonal IgG-1 antibody and has been on the market since February 2004. It is unclear whether patients who have previously progressed on Cmab will benefit from therapy with Pmab. Methods: This is a retrospective analysis of 13 patients previously treated at OSUMC. The primary aim was to assess clinical benefit rate of Pmab in patients who failed Cmab. Patients were identified through our database from Sep 2006 until Dec 2011. Patient characteristics, length of treatment duration, response rate, and time elapsed from Cmab to Pmab were recorded. Clinical benefit (CR, PR, SD) was assessed by RECIST criteria. CEA was recorded. Results: Median age was 61 years (range 29-80), 8 males and 5 females. One patient had one FU-based line of chemotherapy while 12 patients had two FU-based lines of chemotherapy before starting Pmab. Five patients were KRAS wild-type, 8 were unknown. Five patients got Pmab as a single agent, 6 with FOLFIRI, 1 with irinotecan and 1 with capecitabine. Median time elapsed from stopping Cmab to starting Pmab was 4 months (range 0-25 months). One patient had a partial response to Pmab, 6 had stable disease, 2 had progressive disease and 4 patients did not have imaging studies. CEA decreased in 7 patients with mean decrease of 55% (SD +/- 34%). Median time to progression on Pmab was 5 months (range 1-13 months). Of 3 patients without clinical benefit to Cmab, 2 (67%) had clinical benefit from Pmab. Of 8 with clinical benefit to Cmab, 5 (63%) had clinical benefit from Pmab. Median duration of time from stopping Cmab to starting Pmab was similar for responders (3.5 months) and nonresponders (2.5 months). Conclusions: Our data suggest that Pmab can be given to patients previously treated on Cmab with clinical benefit seen in 2/3 of cases. Of interest, patients who did not have clinical benefit from Cmab did so with Pmab in 2/3 of cases.