bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival trends of 89,543 patients with metastatic colorectal cancer: A population-based analysis.
Authors: Guller Ulrich , Tarantino Ignazio , Castleberry Anthony W. , Brugger Lukas , Koeberle Dieter , Cerny Thomas , Pietrobon Ricardo , Mantyh Christopher , Worni Mathias 
Published: February 2017

476 Background: Metastatic colorectal cancer remains among the most common causes for cancer death and is a major public health problem. While overall survival improvements have been achieved in clinical trials, it is unknown how much this progress translated into increased survival on a population-based level. Methods: The SEER (Surveillance Epidemiology and End Results) registry was queried from 1988 to 2008. Patients with metastatic colorectal cancer were included. Multivariable adjusted Cox proportional hazards regression analyses were used. Results: In total, 89,543 patients were included. Median age was 67.1 years, 47.2% were female, 79.7% Caucasian. Median overall survival was 11 months, which increased from 8 months in 1988 to 14 months in 2008 (75% increase). In patients <= 65 years, overall survival increased from 9 months in 1988 to 20 months in 2008 (122% increase), in patients above 65 years from 7 months in 1988 to 9 months in 2008 (29% increase). In Cox proportional analyses, later year of treatment (hazard ratio=HR: 0.973 per year [95% CI: 0.972-0.975], p<0.001), tumor location in the rectum (HR: 0.72 [95% CI: 0.71 - 0.74]; p<0.001), married civil status (HR: 0.85, [95% CI: 0.84 - 0.86]; p<0.001), and cancer-directed surgery (HR: 0.44, [95% CI: 0.43 – 0.45]; p<0.001) were associated with better overall survival, while patients above 65 years (HR: 1.48, [95% CI: 1.46 - 1.51]; p<0.001) and African-Americans (HR: 1.08, [95%CI: 1.06 - 1.11], p<0.001) had worse survival. Conclusions: Tumor location in the rectum, married civil status and cancer-directed surgery are associated with significantly improved overall survival while elderly and African-Americans have worse outcomes. Moreover, a statistically significant and clinically relevant overall survival increase from 1988 to 2008 was found for metastatic colorectal cancer patients. However, most progress is observed in patients aged below 65 years, while the overall survival increase in the elderly is modest. Further studies among elderly patients assessing the reasons for the lack of a parallel survival increase are warranted.
Is adjuvant oxaliplatin (Ox) overutilized in colon cancer (CC)? 408 cases from the practices of 102 oncologists.
Authors: Love Neil , Grothey Axel , Venook Alan Paul , Hussein Atif Mahmoud , Moss Jonathan , Ziel Kathryn 
Published: February 2017

479 Background: Recent long-term clinical trial follow-up suggests that adding Ox to a fluoropyrimidine (FP) may provide less benefit in adjuvant CC than originally believed (Tournigand JCO 2012). In addition, emerging data on tissue biomarkers such as microsatellite mismatch repair (MMR) and the 12-gene Recurrence Score (RS) suggest these assays may be helpful in better defining treatment benefit, and a new report provides evidence that RS may specifically predict the value of Ox. (O’Connell ASCO 2012) In view of these developments we sought to document current use of adjuvant chemotherapy and physician perceptions about these decisions. Methods: US-based oncologists were recruited to complete a survey and contribute treatment data for their last 3 patients (pts) with stage II disease and last pt with a stage III tumor. Results: 25 gastrointestinal cancer clinical investigators and 77 practicing oncologists participated, providing data from a total of 408 cases (92% treated since 2011). Findings from the 2 groups are similar and are presented in aggregate. A median of 9 and 15 pts annually were evaluated with stage II and III tumors, respectively. Clinicians stated that they require a median of a 5% absolute reduction in relapse rate to use a FP alone and an additional 5% reduction to add Ox. Ox/FP was administered to 95 of 102 pts with stage III tumors (93%) and 85 of 306 pts with stage II disease (28%), particularly to those under age 70 or with T4 tumors (Table). MMR was evaluated in 127 pts (42%) with stage II and 20 pts (20%) with stage III disease. RS was obtained for 46 pts (15%) with stage II tumors, but only 2 pts (2%) with stage III. Conclusions: Adjuvant Ox is employed extensively in spite of the fact that it may provide less benefit than many oncologists report requiring to initiate its use. However, several recent research developments may be laying the groundwork for a change in this treatment practice. [Table: see text]
Natural history and outcomes in a population-based cohort of synchronous and metachronous colorectal cancers (CRC).
Authors: Chu Jackson , Goktepe Ozge , Cheung Winson Y. 
Published: February 2017

485 Background: Early data suggest that synchronous and metachronous CRC may portend a worse prognosis when compared to solitary CRC. Our study objectives were to 1) characterize the clinical features and treatment patterns of synchronous and metachronous CRC and 2) compare their survival outcomes with those of solitary CRC. Methods: All patients diagnosed with either synchronous or metachronous CRC between 1999 and 2008 and referred to 1 of 5 regional cancer centers in British Columbia were reviewed. Synchronous and metachronous CRC were defined as multiple (2 or more) distinct tumors that were diagnosed within and beyond 6 months of the date of index CRC diagnosis, respectively. Patients with liver metastases at initial diagnosis were excluded. Kaplan-Meier and multivariate Cox regression analyses were used to estimate survival for synchronous and metachronous CRC, and to compare outcomes with solitary CRC. Results: A total of 213 patients with 388 synchronous and 69 metachronous cases of CRC were included: median age was 70 (range 26-94), 55% were men, and 30% were ECOG 0 to 1 at index diagnosis. At initial presentaiton, 35% and 51% of patients who manifested with synchronous and metachronous tumors, respectively, were TNM stage III. Concurrent colorectal adenomas were found in 45% of synchronous and 33% of metachronous cases. The most prevalent symptoms experienced by patients included changes in bowel movements and abdominal pain. The majority of patients underwent a curative resection (99% of synchronous and 97% of metachronous). Adjuvant chemotherapy was used to treat 44% of both synchronous and metachronous tumors. Compared to solitary CRC, patients with synchronous and metachronous CRC had similar 3-year relapse-free survival (66 vs. 66 vs. 56%, p=0.20), 5-year cancer-specific survival (69 vs. 67 vs. 53%, p=0.34), and 5-year overall survival (62 vs. 59 vs. 49%), p=0.74. Similar observations persisted in the multivariate Cox regression model. Conclusions: There appears to be no differences in survival outcomes in patients with solitary, synchronous, or metachronous CRC. Patients who present with multiple CRC tumors should be managed similarly to those who only present with an isolated tumor.
A phase II trial of combination oxaliplatin, capecitabine, and celecoxib with concurrent radiation for patients with newly diagnosed resectable rectal cancer.
Authors: Murad Waheed , Fekrazad M Houman , Schrader Ronald , Liem Benny J. , Patt Yehuda Z. , Lee Fa-Chyi 
Published: February 2017

487 Background: The goal of preoperative chemoradiation in rectal cancer is complete surgical resection without impairing sphincter function and to decrease local recurrence. The primary objective of the study was to determine complete pathological response rate (pCR) with capecitabine, oxaliplatin and celecoxib with concurrent radiation therapy. The secondary objectives were down staging rate, sphincter preservation rate, incidence and severity of adverse events. Methods: A total 37 out of 55 planned patients (pts) were enrolled by New Mexico cancer center consortium from 2005 to 2012. Inclusion criteria were: Resectable adenocarcinoma of the rectum within 12 cm of the anal verge, biopsy proven T3-4 N1-2 M0 based on endoscopic ultrasound, performance status of 0-2, adequate bone marrow reserve and liver functions. The neoadjuvant chemoradiation treatment was: capecitabine 850 mg/m2 bid Monday through Friday for 5 weeks, weekly oxaliplatin 50 mg/m2 IV, celecoxib 200 mg bid with concurrent 45 gray radiation therapy in 25 fractions over 5 weeks. Results: Only 21 of 37 pathology reports were assessable for the primary objective of pCR. 7/21 pts (33%, 95% CI, 0.14-0.56) had pCR and 4 had only microscopic residual disease. Thus, 11/21 pts (52%, 95% CI, 0.30-0.74) had an excellent response following chemoradiation. The secondary outcome analysis showed 19/21 pts (90%, 95% CI, 0.69-0.98) were down staged. Sphincter preservation rate was 71% (15/21) (95% CI, 0.47-0.88). Grade 3 and 4 toxicities were observed in 23% and included nausea, vomiting, diarrhea, dehydration, hypokalemia, lymphopenia and fatigue. Conclusions: We report the highest pathological CR so far in stage III rectal cancer with these early results. This could be due to anti-inflammatory activity of celecoxib leading to better tolerance of radiation therapy and possible synergistic anti-tumor activity. Final results will be reported upon completion of the trial. Clinical trial information: NCT00250835.
Investigation of thrombospondin 1 (THBS1) as prognostic and predictive factor of neoadjuvant chemotherapy for advanced gastric cancer.
Authors: Matsumoto Noriko 
Published: February 2017

49 Background: Curative R0 operation is the best treatment for patients with Stage II/III gastric cancer, but still there are recurrent cases. Although chemotherapy is an important treatment, there is no evidence of neoadjuvant chemotherapy (NAC) for both R0 operated advanced gastric cancer and inoperable cases. Thrombospondin 1 (THBS1) plays a role in angiogenesis in many cancers, and we reported that THBS1 could be prognostic factor of Stage IV gastric cancer and predictive factor of S-1+ paclitaxel chemotherapy. The aim of this study is to investigate THBS1 plays as prognostic and predictive factor of neoadjuvant chemotherapy for advanced gastric cancer. Methods: Study 1. Investigation of THBS1 as prognostic factor in R0 cases: 129 patients with R0 operated for stage II/III gastric cancer (II: 56, III: 73) were enrolled in this study. THBS1 expression was investigated by immunostaining with resected specimen. Relationship between THBS1 expression and disease free survival (DFS), and recurrence rate were evaluated. Study 2. Investigation of THBS1 as predictive factor in unresectable cases: Among 111 patients who had unresectable gastric cancer, 55 patients had NAC (NAC (+) group; S-1+PTX i.p.: 23, Docetaxel+CDDP+S-1 (DCS): 17, S-1+CDDP 6, Docetaxel{S-1 (DS): 5, S-1 alone: 4) were compared with NAC (-) group (n=56) by evaluation of relationship between immunohistological expression of THBS1 and overall survival. Results: Study 1: There were 39 (30%) gastric cancers with positive staining for THBS1, 19 patients (49%) recurred cancer and 5-year DFS was 20% in THBS (+) group. Among 90 patients of THBS (-) group, 19 patients (20%) recurred, and DFS was 73%. Study 2: there were 32 (29%) unresectable gastric cancers with THBS1 (+). NAC (+) group showed 30.4% of 2-year OS, whereas 13.1% of NAC (-) group. Among NAC (+) group, 24 (43.6%) patients showed response of NAC, and among responder group, 13 (54%) patients showed THBS1 (+), whereas 10 (28.6%) patients showed THBS (+) in non-responder group. Conclusions: THBS1 expression showed reverse correlation with prognosis and positive correlation with prediction of neoadjuvant chemotherapy for Stage II/III gastric cancer.
Preoperative chemotherapy prior to pulmonary metastatecomy in patients with prior surgically resected primary colorectal carcinoma.
Authors: Subbiah Ishwaria Mohan , Blackmon Shanda H. , Correa Arlene M. , Kee Bryan K. , Vaporciyan Ara A. , Swisher Stephen , Eng Cathy 
Published: February 2017

490 Background: The exact benefit of preoperative chemotherapy prior to pulmonary metastasectomy for patients with metastatic colorectal carcinoma (CRC) is unknown. Here, we identify outcomes of preop chemo in pts w previously resected primary CRC who then had resectable pulmonary CRC metastases. Methods: We queried a prospectively collected database to identify pts who underwent pulmonary CRC metastasectomy and the specific chemo regimen given prior to but w/i 3 months of surgery. Two multivariate logistic analyses were performed to identify preop regimen as predictors of overall survival (OS) and progression free survival (PFS). Results: From Feb 2000 onwards, 229 pts underwent lung met resection (median age 61, range 24-82). Of those pts, 114 received preop chemo for a median duration of 4months (range 0.1-25.3mos). 41pts receiving 0-3 mos of preop chemo, 37 3-6mos, and 36 >6mos. 38pts received an oxaliplatin-based regimen (23 FOLFOX+bevacizumab [bev], 5 XELOX, 5 FOLFOX alone, 3 FOLFOX+cetuximab, 1 FOLFOX + novel TR-2/DR5 antibody, 1 oxali+irinotecan). 53 pts received an irinotecan-regimen. 29 received a capecitabine therapy. Pts on an oxali-based therapy had an improved OS vs alternate chemo regimen (mean OS 77.6 mos vs 54.2 mos, median OS not reached in oxali-group, p .001). However pts on an irinotecan-based regimen had a lower OS vs alternate chemo (median OS of 49.1mos vs 57.9mos, p .024). 5FU, capecitabine, or bev-based therapies did not significantly impact OS. The type of preop chemo regimen did not significantly affect PFS after lung met resection. Oxali-based regimen moved towards a favorable OS when compared to OS without any preop chemo but not of statistical significance (HR 0.69; 95% CI 0.287 to 1.663, p 0.409) while receiving a non-oxali-based preop regimen was associated with a shorter OS when compared to no preop chemo (HR 2.64; 95% CI 1.634 to 4.275, p <0.001). Conclusions: Preop chemo with an oxaliplatin regimen prior to pulm met resection may improve OS, providing long-term benefit, whereas a preop irinotecan-based therapy appears to result in a shorter OS. Prospective trials on specific preop regimens and criteria for patient selection are planned.
A phase II open-label randomized multicenter trial of TSU-68 in combination with S-1 and oxaliplatin versus S-1 in combination with oxaliplatin in patients with metastatic colorectal cancer.
Authors: Shin Sang Joon , Lee Jeeyun , Chung Ik-Joo , Kim Tae Won , Chun Hoo Geun , Shin Dongbok , Kim Yeul Hong , Song Hong-Suk , Han Sae-Won , Kim Jong Gwang , Kim Sun Young , Choi Young Jin , Chung Hyun Cheol 
Published: February 2017

492 Background: Colorectal cancer (CRC) is the fourth leading cause of cancer-related deaths worldwide. Oxaliplatin-based treatment (FOLFOX, CapeOX) combined with bevacizumab is one of the standard chemotherapies for metastatic CRC. However, several clinical studies performed using S-1 plus oxaliplatin (SOX) indicate that SOX is a treatment option for metastatic CRC. TSU-68 (orantinib) is an oral compound that inhibits vascular endothelial growth factor receptor and platelet-derived growth factor receptor and has promising efficacy and high safety. The recommended phase II dose of TSU-68 plus SOX has been determined in a phase I study. This trial aimed to evaluate the efficacy of TSU-68 in combination with SOX. Methods: We performed an open-label multicenter randomized phase II trial in Korea. Treatment-naive metastatic CRC patients with a performance status 0 or 1 were randomized in a ratio of 1:1 to receive either TSU-68 plus SOX (group A) or SOX (group B). The primary endpoint was progression-free survival (PFS). Results: We randomized 105 patients (52 patients, group A and 53 patients, group B). Median PFS was 7.0 months in group A (hazard ratio [HR], 1.057) and 7.2 months in group B (P = 0.8401). The most frequent grade 3/4 events were thrombocytopenia (9.6% vs 26.4%), neutropenia (13.5% vs 15.1%), and anemia (3.8% vs 13.2%). We observed a difference between the 2 groups in all grades of anemia (15.4% vs 32.1%), diarrhea (30.8% vs 47.2%), vomiting (50.0% vs 26.4%), and chromaturia (23.1% vs 0.0%). Analysis using a COX proportional hazard model showed that baseline interleukin 6 (IL-6) level was associated with survival benefit of TSU-68 (P = 0.012). Conclusions: TSU-68 plus SOX showed a favorable safety profile. However, TSU-68 did not have a synergistic effect on the efficacy of SOX. Baseline serum IL-6 levels could be prognostic factors for TSU-68 efficacy. Further biomarker analysis is being performed to determine the efficacy of this treatment. Clinical trial information: JapicCTI-111403.
Multicenter randomized phase II clinical trial of preoperative chemoradiotherapy by S-1 versus UFT to rectal cancer for personalized therapy (UMIN ID: 000001704).
Authors: Iwata Takashi 
Published: February 2017

499 Background: Preoperative chemoradiotherapy (CRT) in rectal cancer reduces the local recurrence rate after operation and preserves the anus, but it is difficult to predict the effects of CRT. Multicenter randomized phase II clinical trial of preoperative chemoradiotherapy by S-1 vs UFT for rectal cancer was conducted to compare the toxicity and efficacy of CRT using oral DPD-inhibitory fluoropyrimidines (UFT versus S-1, (UMIN ID: 000001704)) in patients with locally advanced rectal cancer. Methods: In this randomized phase II study, during April 2008 to October 2010, rectal cancer patients (n=59) who underwent preoperative CRT were randomly divided into two groups; S-1 group (n=30, 80 mg/m2/day, 5 days/w x 4 w), and UFT (n=29, 300 mg/m2/day, 5 days/w x 4 w). Both groups were combined with 40Gy radiotherapy (2 Gy ×5 days/w × 4 weeks,total 40 Gy). The pathological response rate, clinical response rate by RECIST, and frequency of adverse events of CRT were compared between S-1 group and UFT group. Results: Response to CRT determined by histopathologic examination of surgically resected specimens and RECIST were as follows: responders (grade 2 or 3) were 60% (S-1) and 52% (UFT) (p=0.52). S-1 group showed 54% of response rate in pathological response, whereas UFT group showed 45% (p=0.43). In adverse events, frequence of Grade 2 and 3 diarrhea was significantly higher in S-1 group compared with UFT group. There was no difference between the two groups in compliance (S-1group: 83%, UFT group: 97%). Conclusions: Both S-1 and UFT were safely used for preoperative CRT. S-1 tended to show higher response rate than UFT, although diarrhea in S-1 was higher than in UFT. Clinical trial information: 000001704.
Phase II study to evaluate efficacy and safety of irinotecan, capecitabine, and bevacizumab in metastatic colorectal cancer (mCRC) patients.
Authors: Garcia Alfonso Pilar , Chaves-Conde Manuel , Munoz Andres , Salud Antonia , Garcia-Giron Carlos , Gravalos Castro Cristina , Massuti Bartomeu , González Flores Encarnación , Queralt Bernardo , Lopez Ladron Amelia , Losa Ferran , Oltra Ferrando Amparo , Gomez Reina Maria Jose , Garcia-Carbonero Rocio , Garcia-Escobar Ignacio , Aranda Enrique 
Published: February 2017

501 Background: XELIRI regimen biweekly (combination of capecitabine and irinotecan) is an active and well tolerated treatment for mCRC. Bevacizumab provides significant clinical benefits in previously treated patients with mCRC. On this basis, the aim of this study is to evaluate the efficacy and safety of this combination. Methods: Multicentric, prospective, open-label phase II trial. Treatment scheme: irinotecan (iri) (175mg/m2 d1 q2w) + capecitabine (xel)(1,000mg/m2bid d 2-8) + bevacizumab (bev) (5mg/kg, d1 q2w). Results: 77 patients (p) were evaluated (66.2%, male) with a median age of 65.1 years (41.1-81.1). ECOG performance status was ≤1 in 96.1%. Primary tumor locations were: colon (53.2%), rectum (31.2%), and rectum/colon (15.6%). 27 p (35.1%) received adjuvant chemotherapy. Metastases were detected in liver (62.3%) and lung (54.5%). Mean time in treatment was: 7.1±4.9 months and median of cycles administered was 12(1-43). Median relative dose intensity was 89% for xel and bev and 85% for iri. Best response confirmed were: complete response (5.2%), partial response (32.5%), stable disease (46.8%). After a median of follow-up of 23.3 (0.4-39.6) months, median overall survival (OS) and progression free survival (PFS) was 24.8 and 11.8 months respectively. Analysis on Kras status was done in 71 p. There were no significant differences in OS or in PFS between WT and MUT p. 17 p (22.1%) underwent salvage surgery, 12 of whom had an R0 resection. The most frequent G3-4 toxicities were: diarrhea (18.2%), asthenia (16.9%), pulmonary embolism (13%; in eight of 10 p were asymptomatic), neutropenia (10.4%), febrile neutropenia (6.5%) and HFS (5.2%). Three treatment related deaths were reported (2 cases of multi-organ failure, and 1 case of intestinal perforation). Conclusions: Bevacizumab combined with biweekly XELIRI is an active first-line regimen for mCRC treatment with a feasible and manageable safety profile. Bevacizumab treatment efficacy was independent on Kras status. Clinical trial information: NCT00875771. [Table: see text]
Randomized clinical trial on accelerated hyperfractionated versus hypofractionated preoperative radiotherapy for rectal cancer: A report on perioperative complication rates.
Authors: Wzietek Iwona , Bialas Marcin , Kryj Mariusz , Chmielarz Andrzej , Widel Maciej , Idasiak Adam , Namysl-Kaletka Agnieszka , Stobiecka Ewa , Chmielik Ewa , Wydmanski Jerzy , Suwinski Rafal 
Published: February 2017

506 Background: The aim of the study is to verify hypothesis that accelerated hyperfractionated preoperative radiotherapy for rectal cancer (HART) may provide a favorable long-term tolerance compared to treatment given in higher fraction (fx) doses (HYPO). This report focuses on early outcomes of the study. Comparison of late tissue reactions, evaluation of QLQ and long-term outcome in both trial arms is the ultimate goal. Methods: Between 2005 and 2011, 238 patients (pts) with cT3-4 resectable adenocarcinoma of the rectum were enrolled, which represents app. 70% of an overall trial size. The pts were randomly assigned to HART (n=122) or HYPO (n=116). The pelvis was irradiated 2x/day to the total dose of 42 Gy in 1.5 Gy/fx over 18 days (HART). Patients in HYPO received 39 Gy in 3.0 Gy/fx over 17 days. Postoperative chemotherapy (PCT) was given to ypN+ pts. Results: The actuarial perioperative complication rate at 1 year after treatment was 24.4% vs. 33.4% for HART and HYPO resp. (RR=0.69, p=0.13). The crude rate of pts with any surgical complication during the follow-up (median of 3.1 year) was 32/122 (26.2%) vs. 36/116 (31.0%) for HART and HYPO resp. (p= 0.41). If the values were expr. In terms of number of events (some pts had more than one complication) the rates were 55 events per 122 pts (HART) vs. 63 events per 116 pts (HYPO). Anastomotic leakage appeared in 11/122 HART pts (9.0%) vs. 16/116 in HYPO (13.8%). Anterior resection was performed in 48.8 % vs. 44.1% for HART and HYPO resp. PCT was given to 46.1% of the pts in HART and 45.4% in HYPO. There were no significant differences in 3-year loco-regional control (RR=1.08, p=0.44) and overall survival (RR=0.97, p=0.72) between HART and HYPO, with actuarial rates (for both arms) of 85% and 73% resp. Neither the rate of complicatons, nor type of surgery were influenced by duration of the interval RT-surgery (median 11, Std±18 days) Conclusions: The perioperative complication rate observed had the propensity to favor HART over HYPO, but the differences did not reach the level of statistical significance. Longer follow-up and the analysis encompassing all of the pts enrolled is required to fully address the study endpoints.