bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of HER2 and IGF1 germline polymorphisms with outcome in metastatic colorectal cancer (mCRC) patients (pts) treated with second-line irinotecan (IR) with or without cetuximab (CB): The EPIC experience.
Authors: Yang Dongyun , Bohanes Pierre Oliver , Zhang Wu , Harbison Christopher , Trifan Ovidiu C. , Ning Yan , Benhaim Leonor , Wakatsuki Takeru , El-Khoueiry Anthony B. , Lenz Heinz-Josef 
Published: March 2020

3615 Background: EPIC, a multinational phase III clinical trial with IR + CB vs IR alone in mCRC pts in the second-line setting after failure of FOLFOX demonstrated a benefit for IR+CB in progression-free survival (PFS) and response rate (RR). We evaluated 6 functional germline polymorphisms involved in the IGF1 and HER2 for their potential role as molecular predictors of clinical outcome in pts treated in the EPIC study. Methods: DNA was extracted from all available formalin-fixed paraffin-embedded tumor samples from the EPIC trial. Genotyping was performed using PCR-RFLP assays and 5’ -end [g-33P] ATP’ labeled PCR-protocols. Univariate analysis (Fisher's exact test for RR; log-rank test for PFS and OS) was performed to examine associations between polymorphisms and clinical outcome. Multivariate analysis (Logistic regression or Cox regression model) was conducted to control baseline patient characteristics and treatment. Results: 186 pts with available samples were treated either with IR/CB (arm A, 84 pts) or IR alone (arm B, 102 pts). Median age was 59 yrs (range 34-85yrs) for arm A and 61 yrs (range 25-90 yrs) for arm B. In arm A, 11/84 pts (13%) showed CR or PR, whereas 73/84 (87%) pts had SD or PD. For arm B, 6/102 pts (6%) showed CR or PR, whereas 96/102 pts (94%) had SD or PD. Median PFS for arm A was 3.0 months (95%CI 2.4- 4.1 months) vs 2.7 months (95%CI 2.2-2.9 months) for arm B; median OS was 9.3 months (95%CI 7.1-21.1 months) for arm A vs 12.3 months (95%CI 10.4- 17.9 months) for arm B. KRAS mutation status was not significantly associated with outcome in our patient cohort. We found that HER2 rs 1136201 was significantly associated with response (RR: AA 6.5%, AG 12.5%, and GG 27.3%, Fisher’s exact test p=0.045). IGF1 rs 2946834 was significantly associated with PFS in both univariate and multivariate analyses (median PFS was 2.8 months in patients with CC or CT vs 1.8 months in patients with TT; log-rank p=0.009; Wald test p=0.008). Conclusions: Our study suggests the prognostic value of polymorphisms in the IGF1 and HER2-pathway in mCRC pts treated with IR± CB. Prospective validation of these findings in clinical trials is warranted.
Pharmacogenetic profiling for oxaliplatin-based adjuvant chemotherapy (CT) benefit in stage II-III colon cancer (CC) patients: A GEMCAD study.
Authors: Feliu Jaime , Custodio Ana , Moreno Juan , Aparicio Jorge , Gallego Javier , Yaya Ricardo , Maurel Juan , Fernandez-Martos Carlos , Sánchez Antonio , Calatrava Ana M , Burgos Emilio , Martinez Marín Virginia , De Castro Javier , Barriuso Jorge , Moreno Victor , Hindi Nadia , Madero Rosario , Lapunzina Pablo , Cejas Paloma 
Published: March 2020

3618 Background: Identifying molecular biomarkers for tumour recurrence is critical in successfully selecting early-stage CC patients who are more likely to benefit from adjuvant CT. We tested whether single nucleotide polymorphisms (SNP) within genes involved in biological pathways of interest for CC progression and treatment resistance would predict the risk of recurrence in stage II-III CC patients treated with oxaliplatin and fluoropyrimidines-based adjuvant CT. Methods: Genomic DNA was extracted from formalin-fixed paraffin-embedded samples from 202 surgically treated high-risk stage II (29.7%) and stage III (70.29%) CC patients receiving adjuvant CT (25.24% FOLFOX, 74.75% XELOX) from January 2004 to December 2008. Minimum follow-up was 36 months. Genotyping was performed for 62 SNPs in 31 genes using the MassARRAY (SEQUENOM) technology. Our results were validated in an independent cohort of 177 stage II-III CC. Results: After a median follow-up of 51.4 months (7-96), 63 patients (31.18%) had experienced a relapse and 31 (15.34%) had died. Three-year disease-free survival (DFS) and overall survival (OS) were 72.2% (+/-0.032) and 89.1% (+/-0.022), respectively. Multivariate analysis showed that the risk of recurrence for patients with the E-selectine rs3917412 G>A G/G genotype was higher than for those with any A allele genotype [relative risk (RR): 2.02, 95% confidence interval (CI): 1.09-3.73, p=0.024]. In haplotype analysis, patients harboring the E-selectine rs3917412 G>A G/G and methylentetrahydrofolate reductase (MTHFR) rs1801133 C>T T/T haplotype had a higher risk of developing tumor recurrence compared to the E-selectine rs3917412 G>A any A and/or MTHFR rs1801133 C>T any C haplotype (RR: 3.39, 95% CI, 1.51-7.62, p=0.003). The ability to predict recurrence of this combined analysis was independently validated in the second cohort (RR: 3.75, 95% CI, 1.32-10.68, p=0.013). Conclusions: E-selectine and MTHFR SNPs were found to be independent prognostic markers for stage II-III CC patients, suggesting that this combined analysis provides additional prognostic information to that offered by clinicopathologic variables.
Comparison of incidence and patterns of recurrence in colon cancer (Cca) treated by sentinel lymph node (SLN) mapping (M) versus conventional surgery.
Authors: Shaik Mohammed Saifullah , Kanaan Mohammed Nawaf , Tesfaye Anteneh A. , Nagpal Sunil , Elfakharany Mohamed , Johnston Gregory , Arora Madan L. , Singh T.Trevor , Eilender David S. , Saha Sukamal 
Published: March 2020

3619 Background: Recurrence of Cca patients (pts) depends on the initial stage at diagnosis. SLNM upstages more pts than conventional surgery (Conv. Surg.) for nodal metastasis, this might have an impact on the incidence and pattern of recurrence. Hence comparative study was undertaken for recurrence in Cca pts undergoing SLNM Vs Conv.Surg. Methods: Group (Gp) A pts underwent SLNM with 1% Lymphazurin. The first 1-4 blue nodes were marked as SLNs followed by standard oncologic resection. Gp B pts underwent Conv. Surg. Data was collected for, TNM staging, Recurrence sites and follow up treatment. Minimum follow up of all pts was 12 month, with mean follow up period 44 months for both Gps. Results: There were 357 pts in GpA and 466 pts in GpB. For GpA pts, SLNM was successful in 99.6% of pts with average (Avg.) SLN was 2.8/pts. Avg. no. of LNs in GpA was 15.4/pts vs. 12.8/pt in GpB (p=0.001). For GpA pts, 46% was LN +ve vs 34% in GpB . Excluding T0, Tis and M1 pts at diagnosis, recurrence was calculated for 313 pts in GpA vs. 314 pts in GpB. An overall recurrence was 7.9% in GpA vs 22.2% (p=0.001) in GpB with distant mets being most common in both Gps. Recurrence of LN +ve and LN –ve pts also were significantly lower in GpA vs GpB (Table). The pattern of recurrence between the two Gps is shown in the Table. Conclusions: SLNM upstages significantly more pts in Cca than conv. surg. Even though pattern of recurrence was similar in both Gps, better staging may have resulted in better treatment, reducing the recurrence in SLNM Gp. Hence SLNM may be beneficial for Cca surgery. [Table: see text]
Effect of perioperative complications on recurrence and survival after resection of hepatic colorectal metastases: Analysis of data from a randomized controlled trial.
Authors: Correa-Gallego Camilo , Gonen Mithat , Fischer Mary , Grant Florence , Kemeny Nancy E. , Kingham T. Peter , DeMatteo Ronald P. , Fong Yuman , Allen Peter J , D'Angelica Michael Ian , Jarnagin William R. 
Published: March 2020

3620 Background: Perioperative outcomes such as blood loss, transfusions and morbidity have been associated with cancer specific survival, but this is unsupported by prospective data. Methods: Patients were derived from a previously reported prospective randomized trial of acute normovolemic hemodilution (ANH) versus standard management during major hepatectomy. Patients with metastatic colorectal cancer (mCRC) were selected for analysis. Chemotherapy and survival data were obtained from the medical record. Disease extent was measured using a clinical risk scoring (CRS) system. Log-rank test and Cox proportional hazard model were used to evaluate recurrence free (RFS) and overall survival (OS). Results: This trial enrolled 130 patients, 90 of whom had mCRC. Median follow up was 54 m; median age was 53 yr; 56% were men. The CRS was ≥3 in 55% of patients, and 57% had additional extrahepatic procedures. Morbidity and mortality were 33% and 3%. Chemotherapy was split before and after surgery in 70%; 10% received only preoperative and 19% only postoperative treatment, which was initiated after a median time of 6 wks (IQR = 4-7). RFS and OS were 29 and 59 m. On multivariate analysis, (+) resection margin, high CRS and perioperative complications predicted shorter RFS and OS. Delayed initiation of postoperative chemotherapy (≥ 8 wks) while most common in patients with complications (37 vs 12%; p: 0.01), was not a significant predictor of shorter RFS or OS. Randomization (ANH vs standard) was also not significant in this regard. (See Table.) Conclusions: In this prospective randomized cohort, perioperative morbidity was a highly significant independent predictor of cancer specific outcome, associated with but not entirely explained by delayed initiation of chemotherapy. [Table: see text]
Phase II trial evaluating a 12-week regimen of interdigitating FOLFOX chemotherapy plus pelvic chemoradiation for the simultaneous treatment of primary and metastatic rectal cancer.
Authors: Michael Michael , McKendrick Joseph James , Bressel Mathias , Leong Trevor , Cooray Prasad , Heriot Alexander Graham , Steel Malcolme , Chander Sarat , McClure Bev , Ngan Sam 
Published: March 2020

3629 Background: Current chemotherapy regimens used during chemoradiation (CRT) are adequate for radiosensitization but suboptimal for systemic control. The aim of this study was to assess tolerability, and local/systemic benefits of new regimen delivering intensive chemotherapy and radical radiotherapy in an interdigitating manner. Methods: Phase II prospective study for patients (pts) with untreated simultaneous symptomatic primary and metastatic rectal cancer. The treatment regimen: 12 weeks long. FOLFOX chemotherapy (oxaliplatin 100mg/m2, leucovorin 200mg/m2, 5-FU 400mg/m2 bolus, all day 1, and 5FU continuous infusion [CI] 2.4 g/m2/46 hours) was given in weeks 1, 6, and 11. Pelvic CRT: 25.2 Gy in 3 weeks, 1.8 Gy/fr, with concurrent oxaliplatin 85mg/m2 day 1 and 5-FU CI 200mg/m2/day given in weeks 3-5, and 8-10. Pts received, in 12 weeks, 3 courses of FOLFOX and pelvic radiation 50.4 Gy with concurrent oxaliplatin/5-FU. All pt were staged with CT, MRI and FDG-PET before and post-treatment. Results: 26 pts treated. The mean age was 61 years, 69% male. Rectal primary MRI stage was T2 4%, T3 81% and T4 15%. Liver and lung metastases were present in 81%, and 35% of pts, respectively: 38% of patients had more than one site of metastatic disease. 24 pts (92%) completed the 12-week treatment regimen. All pts received the planned radiation dose. 65% of pts received the planned number of oxaliplatin courses with 88% of pts receiving at least 75% of the protocol oxaliplatin dose. In this 12-week period, grade 3 toxicities were neutropenia 23%, diarrhoea 15%, and radiation perineal skin reaction 12%. Only grade 4 toxicity was neutropenia: 15%. PET metabolic response (CR+PR) rate for rectal primary was 96%. Overall PET metabolic response rate for metastatic disease was 60% (CR rate 16%). Conclusions: It is thus feasible to deliver intensive chemotherapy and radical radiotherapy in an interdigitating manner to treat both primary and metastatic rectal cancer simultaneously. High completion and response rates are encouraging. This regimen is the subject of a current phase II neoadjuvant trial for resectable rectal cancer (TROG 09.01).
Triplet chemotherapy (TC) with FOLFIRINOX regimen in metastatic colorectal cancer (mCRC): Experience of the Val d’Aurelle Center.
Authors: Samalin Emmanuelle , Loriot Virginie , Thézenas Simon , Assenat Eric , Portales Fabienne , Carrere Sebastien , Rouanet Philippe , Bleuse Jean-Pierre , Quenet Francois , Ychou Marc 
Published: March 2020

3633 Background: TC is a treatment option for mCRC to improve the tumor response rate in selected patients (pts) and the conversion rate of initially non-resectable liver metastases. The aim of this study was to evaluate the impact and feasibility of FOLFIRINOX regimen in mCRC pts. Methods: All mCRC pts with non-resectable disease who have received FOLFIRINOX alone or combined with targeted therapies (bevacizumab or cetuximab) from October 2000 to December 2010 were selected for this analysis. Clinical data were collected in a mCRC specific data base and analyzed by the end of 2011. Results: Ninety two pts (52% of men), median age 59 yrs (range: 27-76) were treated with FOLFIRINOX (D1 oxaliplatin 85 mg/m² IV 2H then irinotecan 180 mg/m² IV 90 min and elvorin 200 mg/m², then 5FU 200 mg/m² and 2400 mg/m² by 46H infusion, D1=D15) alone (64%) or combined with cetuximab(30%) or bevacizumab (6%), as 1st-line in 82 pts (89%). Prophyllactic G-CSF was given in 58% of them. Primary tumor was located in colon (58%) or rectum (42%), and 64 (69%) of pts presented with synchronous metastases: liver 100%, lung 40%, peritoneum 17% and nodes 17%. Median number of cures was 8 (range: 1-12). There was 1 toxic death. Grade 3-4 toxicities were: diarrhea 22%, neuropathy 21%, cutaneous 12%, neutropenia 28%, febrile neutropenia 0%, thrombopenia 6%. Objective Response rate according to RECIST criteria was 72% [CI95% 61-81] including 10 pts with complete response (11%). The primary tumor was resected in 70 pts (76%) and 14% had KRAS mutated tumor. Among the pts with liver metastases, 63 (68%) pts were evaluated for secondary resectability by a multidisciplinary committee and 40 pts (43%) had resection achieved (70% R0). Median overall survival was 49 months [CI95%28-62]. Conclusions: These results confirm the feasibility of FOLFIRINOX regimen with or without targeted therapies and its efficacy in terms of response rate and overall survival as 1rst-line treatment in selected mCRC pts.
Intermittent (IAD) versus continuous androgen deprivation (CAD) in hormone sensitive metastatic prostate cancer (HSM1PC) patients (pts): Results of S9346 (INT-0162), an international phase III trial.
Authors: Hussain Maha , Tangen Catherine M. , Higano Celestia S. , Crawford E. David , Liu Glenn , Wilding George , Prescott Stephen , Akdas Atif , Small Eric Jay , Dawson Nancy Ann , Donnelly Bryan J , Venner Peter , Vaishampayan Ulka N. , Schellhammer Paul F. , Quinn David I. , Raghavan Derek , Vogelzang Nicholas J. , Thompson Ian Murchie 
Published: March 2020

4 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Sunday, June 3, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.
Tivantinib (ARQ 197) versus placebo in patients (Pts) with hepatocellular carcinoma (HCC) who failed one systemic therapy: Results of a randomized controlled phase II trial (RCT).
Authors: Rimassa Lorenza , Porta Camillo , Borbath Ivan , Daniele Bruno , Salvagni Stefania , Van Laethem Jean Luc , Van Vlieberghe Hans , Trojan Jorg , Kolligs Frank T , Weiss Alan , Barahona Nancy , Gasbarrini Antonio , Lencioni Monica , Pande Amitkumar U. , Lamar Maria , Chen Yinpu , Schwartz Brian E. , Abbadessa Giovanni , Santoro Armando 
Published: March 2020

4006 Background: Tivantinib (T) is a selective, oral inhibitor of c-Met, the tyrosine kinase receptor for hepatocyte growth factor involved in tumor cell migration, invasion, proliferation and angiogenesis. T has shown promising results in HCC in phase 1 studies as monotherapy and in combination with sorafenib. Methods: This multi-center RCT, enrolled pts with unresectable HCC, 1 failed systemic therapy, ECOG PS <2. Child-Pugh B-C were excluded. Pts were randomized 2:1 to oral T {360 mg bid (A), 240 mg bid (B)} or placebo (P), stratifying by PS and vascular invasion (VI). Treatment continued until disease progression (PD) or unacceptable toxicity. RECIST 1.1 response was evaluated by CT / MRI every 6 weeks. Crossover to open-label T was allowed after PD. Primary endpoint was time to tumor progression (TTP) in the intent-to-treat (ITT) population by central radiology review. Other endpoints included disease control rate (DCR), PFS, OS, efficacy in Met+ (Met ≥ 2+ in >50% of tumor at immunohistochemistry) pts, safety. Results: Characteristics of the 107 enrolled HCC pts (A= 38, B= 33, P= 36) in T/P: 58/28 male; median age 70/68; PS 0 41/21; VI 22/13; Met+ 22/15; Met- 27/13. Dose A was reduced to B in all pts due to G≥3 neutropenia (NEUT) rate. Major TTP, DCR and PFS benefits were obtained in Met+ pts, with preliminary OS trend favoring T (HR=0.47) and no detrimental effect in Met- pts. DCR (95% CI) in T/P was 44 (31-56) / 31(16-48)% for ITT and 50 (28-72) / 20 (4-48)% in Met+ pts. Most common AEs in T were asthenia (26.8%), NEUT (25.4%), low appetite (25.4%); most common drug-related AEs were NEUT (25.4%), anemia (15.5%). Most frequent drug-related serious AE was neutropenic sepsis (4.2%). Efficacy was similar in A / B with less frequent NEUT in B (21.1% / 6.1%). Final OS, PK, biomarker data will be presented. Conclusions: Compared to P, T significantly benefited second-line HCC pts, especially if Met+, with manageable safety profile at 240 mg BID. [Table: see text]
Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal poorly differentiated neuroendocrine carcinoma: The NORDIC NEC study.
Authors: Sorbye Halfdan , Welin Staffan , Langer Seppo W. , Vestermark Lene Weber , Holt Nanna , Osterlund Pia J. , Dueland Svein , Hofsli Eva , Guren Marianne Gronlie , Ohrling Katarina , Birkemeyer Elke , Thiis-Evensen Espen , Biagini Matteo , Gronbaek Henning , Soveri Leena-Maija , Olsen Ingrid Holst , Federspiel Birgitte , Assmus Joerg , Janson Eva Tiensuu , Knigge Ulrich 
Published: March 2020

4015 Background: Gastrointestinal poorly differentiated neuroendocrine carcinoma (GI-NEC) are aggressive tumors with Ki-67>20% and usually metastatic at diagnosis. Knowledge about GI-NEC is limited. We retrospectively reviewed clinical data to identify predictive and prognostic markers for advanced GI-NEC patients. Methods: Epidemiological, biochemical, histopathological, treatment and survival data were registered for advanced GI-NEC patients diagnosed during 2000-2009 at 12 Nordic university hospitals. Results: 305 patients were included. Palliative chemotherapy was given to 252 patients, median survival was 11 months. Response rate to 1st-line chemotherapy was 31%, 33% had stable disease. Ki-67<55% was by ROC analyses the best cut-off value concerning correlation to response rate. Response rate to platinum-based chemotherapy was lower in patients with Ki-67<55% (14% vs.44%, p<0.001). Response rate for 84 patients given 2nd-line chemotherapy was 18%, whereas 33% achieved SD. The most important negative prognostic factors for survival were poor performance status, primary colorectal tumors, and elevated baseline platelets or lactate dehydrogenase (LDH) levels. Patients with Ki-67<55% had longer median survival (15 months) than patients with Ki-67>55% (10 months) (p<0.001). Survival and response rates did not differ between the different platinum chemotherapy schedules (cisplatin-based vs. carboplatin-based) or morphology subtypes. 53 patients received best supportive care only with a median survival of 1 month. Conclusions: This is, to our knowledge, the largest study reporting patient and tumor characteristics, treatment and survival in advanced GI-NEC. Performance status, location of primary tumor and blood levels of platelets and LDH were the strongest prognostic factors for survival. Patients with Ki-67<55% had significantly longer survival than patients with higher Ki-67, but were less responsive to platinum-based chemotherapy. Our data indicate that to consider all GI-NEC as one single disease entity may not be correct.
Correlation of hand-foot skin reaction (HFS) with treatment efficacy in pancreatic cancer (PC) patients (pts) treated with gemcitabine/capecitabine plus erlotinib: A subgroup analysis from the AIO-PK0104 randomized, cross-over phase III trial in advanced PC.
Authors: Haas Michael , Boeck Stefan Hubert , Laubender Ruediger Paul , Modest Dominik Paul , Vehling-Kaiser Ursula , Waldschmidt Dirk , Kettner Erika , Maerten Angela , Winkelmann Cornelia , Klein Stefan , Kojouharoff Georgi , Gauler Thomas C. , Von Weikersthal Ludwig Fischer , Clemens Michael , Geissler Michael , Greten Tim F , Hegewisch-Becker Susanna , Rubanov Oleg , Mansmann Ulrich Robert , Heinemann Volker 
Published: March 2020

4023 Background: AIO-PK 0104 investigated the efficacy and safety of gemcitabine/erlotinib (G/E) followed by capecitabine (C) vs. C/E followed by G. The present subgroup analysis evaluated the correlation between C-associated skin toxicity and outcome parameters in PC. Methods: Within this multicenter phase III trial, pts with confirmed advanced PC were randomly assigned to 1st-line treatment with either C (2,000 mg/m2/d, d1-14 q d21) plus E (150 mg/d, arm A) or G (1,000 mg/m2 over 30 min weekly x 7, then d1, 8, 15 q d28) plus E (150 mg/d, arm B). A cross-over to either G (arm A) or C (arm B) was performed after treatment failure (e. g. disease progression or unacceptable toxicity). Time to treatment failure after 1st- and 2nd-line therapy (TTF2) was the primary study endpoint. Treatment-related skin toxicity was evaluated separately for each treatment arm/each regimen based on NCI-CTCv2. Results: Of 279 eligible pts, 47 had locally advanced, 232 had metastatic disease and 141 pts received second-line chemotherapy. For the present subgroup analysis data on skin toxicity were available from 255 pts. For the 73 pts (29%) with a HFS (any grade documented at any time during the treatment strategy), TTF2 and OS both were significantly prolonged compared to pts without HFS (7.4 vs 4.0 months, p<0.001 and 9.7 vs 5.5 months, p=0.002, respectively). Considering HFS during 1st-line treatment in 123 pts within the CE arm, these results could be confirmed for the 47 pts (38%) with a documented HFS of any grade (TTF2: 7.6 vs. 3.2 months, p<0.001; OS: 10.2 vs. 4.4 months, p=0.001). In pts receiving 1st-line treatment with G/E (n=132) no difference in outcome was observed for pts with (n=13) or without (n=119) HFS of any grade (TTF2: 5.7 vs. 4.2 months, p=0.375; OS: 8.4 vs. 6.6 months, p=0.505). Conclusions: The current subgroup analysis of AIO-PK0104 supports the assumption of a correlation between HFS in PC pts treated with capecitabine or capecitabine/erlotinib and efficacy endpoints like TTF2 and OS. A capecitabin-associated HFS thus might be predictive for efficacy in patients with advanced PC.