bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utilization rates and outcomes of short-course radiotherapy for nonmetastatic rectal adenocarcinoma for patients in the National Cancer Database.
Authors: Elhalawani Hesham , Allen Pamela , Abdel-Rahman Omar Mohammed , Holliday Emma Brey 
Published: January 2019

774 Background: Short-course radiation therapy (SCRT) has been studied in European trials but is not often utilized in the US. We aim to describe the utilization and outcomes of SCRT compared to the more widely used long-course (LCRT) neoadjuvant regimen. Methods: The National Cancer Database (NCDB) was queried for patients treated with preoperative RT followed by surgical resection for non-metastatic rectal adenocarcinoma from 2004-2014. Patient, tumor and treatment-related characteristics were compared between those treated with SCRT (defined as patients receiving < 26 Gray (Gy) in < 7 fractions) and those treated with LCRT. Survivals were compared using the Log-Rank test. Univariate and multivariate Cox regression analyses were used for univariate analysis of factors associated with overall survival (OS). Results: 48898 patients were included for analysis: 48396 patients (99.0%) treated with LCRT and 502 (1.0%) treated with SCRT. Patients treated with SCRT were older (median [range] age 67 [21-90] vs 60 [18-90]; p < .001), had more comorbidities (Charlson/Deyo score 1+ N = 155 (30.9%) vs N = 9795 (20.2%); p < .001), had earlier T-stage (T1-2 N = 141 (28.1%) vs N = 5774 (11.9%); p < .001) and were more likely to be clinically node-negative (N = 324 (64.5%) vs N = 22701 (46.9%); p < .001). Patients treated with SCRT were more likely to be treated after 2009 (N = 303 (60.4%) vs N = 24834 (51.3%); p < .001) and were more often treated at an academic center (N = 318 (63.3%) vs N = 20375 (42.1%); p < .001). Patients treated with SCRT had a 2- and 5-year OS of 85.8% and 65.7%, respectively, compared with 90.9% and 73.5% in patients treated with LCRT (log-rank p < .001). On univariate analysis, receipt of SCRT was associated with worse OS (HR 1.40 95% CI 1.18-1.65; p < .001). However, when entered into a multivariate model including other patient and tumor-related factors, SCRT was actually associated with improved OS (HR 0.77 95% CI 0.59-1.00; p = .048). Conclusions: SCRT is utilized for approximately 1% of patients treated with preoperative treatment of non-metastatic rectal cancer in the US. The results of recently completed randomized trials may further inform patterns of practice in the US and abroad.
Impact of pelvis irradiation on toxicity of further oxaliplatin-based chemotherapy in rectal cancer.
Authors: Spalek Mateusz , Michalski Wojciech , Bujko Krzysztof , Wyrwicz Lucjan 
Published: January 2019

777 Background: Radiotherapy is used in the neoadjuvant setting in majority of rectal cancer patients, while its effect on overall survival is limited mostly to patients with threatened resection margin. Preoperative pelvic irradiation might damage bone marrow. In consequence, relative dose intensity (RDI) and efficacy of further adjuvant or palliative CT might be reduced. The aim of the study was to assess whether radiation damage to the pelvic bone marrow influences the tolerance of further oxaliplatin-based CT. Methods: We have performed the cohort analysis of patients with adenocarcinoma of rectum or colon receiving FOLFOX-4 chemotherapy in adjuvant or palliative setting between 2011-2016. Oxaliplatin relative-dose intensity (RDI) within 8 weeks from the beginning of CT was calculated for each patient. The major factors, which can reduce oxaliplatin RDI, were analyzed independently (hemathological toxicity, neurological toxicity, occurrence of hypersensitivity reactions to oxaliplatin). The data regarding the first disruption of oxaliplatin dose within all planned courses of FOLFOX-4 was also collected. Results: 220 patients met eligibility criteria. 41 of them received neoadjuvant radio(chemo)therapy (study group), the remaining 179 patients were assigned to control group (n = 179). RDI did not differ significantly between irradiated and non-irradiated patients (p = 0.794). There were no statistically significant differences in observed oxaliplatin-related toxicities. The median time between the start of chemotherapy and the first disruption of oxaliplatin administration was also not statistically different between the two groups (p = 0.156). Conclusions: An impact of preoperative radio(chemo)therapy on RDI or tolerance of FOLFOX was not found in rectal cancer.
Clinicopathologic characteristics and impact of oophorectomy for ovarian metastases (ovmets) in colorectal cancer (CRC).
Authors: Ursem Carling Jade , Zhou Margaret , Paciorek Alan T , Atreya Chloe Evelyn , Ko Andrew H. , Zhang Li , Van Loon Katherine 
Published: January 2019

779 Background: As overall survival (OS) with metastatic colorectal cancer (mCRC) and imaging modalities improve, detection of ovmets may be increasing. The ovary is often a sanctuary site for mCRC; however, there is a paucity of data to guide decision-making regarding the role for oophorectomy. Methods: This is a single-institution retrospective review of patients (pts) who received care for mCRC (incl. appendiceal primaries) with ovmets from 2009-2017. Pts were identified through a hospital-based cancer registry, provider recall, and pathology and radiology databases. Clinicopathologic and treatment data were abstracted. Cox proportional hazards models were used to evaluate for associations with OS. Results: Of 108 pts, median age was 50 (range 19-106), 62 (57%) were Caucasian, and 69 (64%) had ovmets at initial CRC diagnosis. Primary tumor location was left-sided in 54 (50%), right-sided in 27 (25%), appendiceal in 18 (17%), and unknown in 9 (8%). Median OS from diagnosis of mCRC was 29.6 months (mo) with median follow-up of 21.9 mo (range 0.77-172.47). Younger age, absence of signet-ring or mucinous features, well/moderately differentiated grade, and resection of primary tumor were associated with improved OS (p < 0.05). Of 83 (76%) pts who underwent oophorectomy median OS was 36.7 mo vs. 25 mo in those who underwent non-operative management (HR 0.54, 95% CI 0.31-0.94, p = 0.03). Among 94 pts with extra-ovarian disease, 70 (74%) underwent oophorectomy; however, no significant difference in median OS was detected vs. those who did not (30.9 vs 25.0 mo, p = 0.07). In a multivariate model, oophorectomy was not associated with OS (HR 0.63, 95% CI 0.29-1.36, p = 0.24). Conclusions: While ovmets have been previously reported as associated with a poor prognosis, the median OS for this cohort was comparable to existing OS data for mCRC pts. Although oophorectomy for ovmets from mCRC was associated with improved OS in univariate analysis, this effect was not significant in the presence of extra-ovarian metastases. Ovmets from mCRC remain a difficult challenge in clinical care. Oophorectomy may improve OS in select cases; however, further evaluation of predictors of benefit is needed.
Regorafenib in antiangiogenic-naive, chemotherapy-refractory advanced colorectal cancer: A phase IIb trial.
Authors: Riechelmann Rachel Pimenta , Leite Luiz Antonio Senna , Glasberg Joao , Bariani Giovanni Mendonca , Rivelli Thomas Giollo , Nebuloni Daniela R. , Puty Fabiola , Kappeler Christian , Pereira Kaline M. C. , Queiroz Marcelo A , Hoff Paulo Marcelo 
Published: January 2019

782 Background: The oral multikinase inhibitor regorafenib improves overall survival in advanced colorectal cancer (CRC). The aim of this study was to investigate the safety and efficacy of regorafenib in antiangiogenic-naïve patients with chemotherapy-refractory CRC. Methods: In this single-center, single-arm, phase 2b study, patients received regorafenib 160 mg/day for 3 weeks on/1 week off. Tumor response assessed by RECIST 1.1 and tumor metabolic response by [18F] fluorodeoxyglucose positron emission tomography (PET/CT) according to the European Organization for Research and Treatment of Cancer (EORTC) criteria were evaluated at week 8 (W8). PFS rate was defined as the percentage of evaluable patients alive without progression at W8. Safety was assessed until the cut-off date (May 2, 2017). Results: Overall, 59 patients (59.3% male; median age 58.0 yrs) received regorafenib (median dose 148.8 mg/day). The W8 PFS rate was 46.6% (95% CI 33.3% - 60.1%) and median PFS and OS were 3.6 and 7.5 months, respectively. Overall disease control rate (DCR) was 50.8% by RECIST and 62.7% by EORTC criteria (Table). Most common regorafenib-related grade ≥3 AEs were hypertension (35.6%), hand-foot skin reaction (HFSR) (25.4%) and hypophosphatemia (22.0%). One patient discontinued treatment due to drug-related HFSR. Conclusions: The W8 PFS rate and overall DCR support the anti-tumor activity of regorafenib in antiangiogenic-naïve, chemotherapy-refractory advanced CRC. Compared with the previous phase 3 CORRECT and CONCUR trials, the median PFS suggests a better outcome in this population. These data provide the basis for further investigation of regorafenib’s role in earlier treatment lines in metastatic CRC and on the use of PET/CT in tumor response assessment. Clinical trial information: NCT02465502. [Table: see text]
Efficacy of adjuvant chemotherapy after resection of pulmonary metastasis from colorectal cancer: A propensity score matching analysis.
Authors: Imanishi Mamiko , Yamamoto Yoshiyuki , Hamano Yukako , Yamada Takeshi , Moriwaki Toshikazu , Gosho Masahiko , Sakao Yukinori , Okumura Takehiro , Boku Narikazu , Kondo Haruhiko , Hyodo Ichinosuke 
Published: January 2019

788 Background: A number of retrospective studies reported that 5-year survival rate was 30-60% in patients who underwent curative resection of pulmonary metastases (PM) from colorectal cancer (CRC), and PM-CRC resection was recommended in clinical practice. Efficacy of adjuvant chemotherapy after resection of PM remains unclear. Therefore, using a large-scale data obtained from patients who underwent R0 resection of PM in Japan, we investigated it with a propensity score-matching analysis. Methods: We retrospectively collected clinical data of 1237 patients who underwent metastasectomy of PM-CRC at 46 Japanese institutions from 2004 to 2008. Excluding non-curative resection, preoperative chemotherapies, extra-thoratic metastases, complications after surgery, and inadequate data, 530 patients’ data (surgery alone 269 and surgery with adjuvant chemotherapy 261) were used for the matching. Patient backgrounds affecting doctor’s recommendation of adjuvant chemotherapy and including commonly reported prognostic factors were adjusted, using a propensity score-matching method. Primary and secondary endpoints were overall survival (OS) and disease-free survival (DFS), respectively. Results: After the matching with propensity-score, 167 patients for each group were selected. Patient backgrounds were balanced between both groups. Adjuvant chemotherapies were fluorouracil alone (67%), oxaliplatine-containing regimen (24%), irinotecan-containing regimen (7%) and others (2%). There were no significant differences between both groups in OS (HR 0.97, 95%CI 0.64-1.46, p = 0.88) and DFS (HR 0.99, 95%CI 0.75-1.32, p = 0.96). Conclusions: A propensity score-matching analysis did not show a survival benefit of adjuvant chemotherapy after resection of PM in patients with CRC. A large prospective observational study with high quality or randomized clinical trial is needed.
Comparative analysis of different maintenance regimens after first-line induction in patients with metastatic colorectal cancer.
Authors: Mohamed AMR , Abdallah Nadine , Ismail Hibah , Chen Wei , Jang Hyejeong , Smith Daryn W. , Akhras Alaa , Tesfaye Anteneh A. , Philip Philip Agop , Shields Anthony Frank 
Published: January 2019

789 Background: Although, previous trials have demonstrated the benefits of maintenance chemotherapy for unresectable metastatic colorectal cancer (MCRC), the optimal maintenance regimen with acceptable safety profile is still undetermined. The primary objective of this meta-analysis was to compare the effectiveness of the most common clinically used maintenance regimens after first line therapy in MCRC. Methods: Among 52 prospective studies published 2009-2017, 14 were qualified for inclusion. Random-effect model was used for pooled effects within different categories include those with no maintenance treatment versus different maintenance regimens (Bevacizumab, capecitabine, bevacizumab plus capecitabine, bevacizumab plus erlotinib, and cetuximab). Primary endpoint was median progression free survival (PFS), and secondary endpoint was median overall survival (OS). All statistical tests were two-sided and p values < 0.05 were considered significant. Results: 14 studies with 3553 patients (57% males) were included in final analysis. Induction treatment was 5-FU or capecitabine - based chemotherapy with either oxaliplatin or irinotecan with or without bevacizumab. After stratifying for induction status, patients who did not receive treatment had worse PFS compared to maintenance treatment [pooled median PFS 3.52 months, 95% CI (2.97- 4.07) Vs 5.08 months, 95% CI (4.59- 5.57), z-test adjusted p-value 0.0005]. Among different maintenance regimens, capecitabine /bevacizumab combination showed better PFS [pooled median PFS 6.87 month, 95% CI (5.17- 8.57)], however the results were not significant (z test adjusted p-value 0.1383). No statistical significant difference in median OS between maintenance regimens. Conclusions: MCRC patients who did not receive maintenance treatment had shorter PFS. Although the superiority of bevacizumab plus capecitabine maintenance cannot be confirmed, there was a trend towards better PFS. This study suggests that bevacizumab plus capecitabine may be an appropriate maintenance option after first induction therapy depending on the tolerability and compliance with oral capecitabine.
Relations of carcinoembryonic antigen (CEA) staining of cancer tissue and serum CEA levels to histologic response in patients with locally advanced rectal cancer (LARC) who received neoadjuvant chemoradiotherapy (nCRT).
Authors: Saito Gota , Sadahiro Sotaro , Miyakita Hiroshi , Okada Kazutake , Tanaka Akira , Suzuki Toshiyuki 
Published: January 2019

790 Background: Neoadjuvant chemoradiotherapy (nCRT) is a standard of care for LARC. The serum CEA level is a predictor of the response to nCRT; however, the relation between CEA production immunohistochemically evaluated in cancer tissue and treatment response remains unclear. Methods: The study group comprised 145 patients with clinical Stage II/III rectal cancer who received nCRT followed by surgery from 2005 through 2013. The radiation dose was 40 to 45 Gy. UFT- or S-1-based chemotherapy was given concurrently. Surgery was performed 6 to 8 weeks after the completion of radiotherapy. Immunohistological CEA staining patterns in biopsy tissue obtained before nCRT were evaluated. Specimens in which the luminal cell membrane or the cytoplasm was strongly stained were defined as staining positive. The histologic response was evaluated on the basis of the pathological complete response (ypCR) rate, T downstaging, tumor regression grade (TRG), and tumor shrinkage rate on MRI. Results: CEA staining in biopsy specimens and serum CEA levels were both negative in 17 patients (11.7%) and both positive in 72 patients (49.7%). There was no relation between the groups (p = 0.174). In patients with negative CEA staining, the rates of ypCR, T downstaging, marked regression, and mean tumor shrinkage were 24.3%, 51.4%, 45.9%, and 72.3%, respectively. In patients with positive CEA staining, these rates were 11.1%, 48.1%, 37.0%, and 72.8%, respectively. CEA staining of cancer tissue was not significantly related to the ypCR rate, T downstaging, a marked regression rate, or the tumor shrinkage rate on MRI (p = 0.060, p = 0.849, p = 0.436, and p = 0.874, respectively). Patients with negative serum CEA levels before nCRT had significantly higher rates of ypCR, T downstaging, marked regression, and tumor shrinkage on MRI than did patients with positive serum CEA levels (p = 0.014, p = 0.006, p = 0.002, and p = 0.014, respectively). Conclusions: Serum CEA levels before nCRT were a significant predictor of the histologic response to nCRT; in contrast, tissue CEA staining before nCRT was unrelated to the histologic response to nCRT.
The effect of dose escalation for large squamous cell carcinomas of the anal canal: A National Cancer Database study.
Authors: Prasad Rahul Neal , Elson Joshua , Kharofa Jordan 
Published: January 2019

791 Background: Chemoradiation allows for organ preservation in patients with anal cancer, but patients with large tumors (T3/T4) continue to have high rates of locoregional recurrence. With conformal radiation techniques, there is interest in dose escalation to improve local control for large tumors. Methods: The National Cancer Database (NCDB) was used to identify patients with anal cancer from 2004-2013 with tumors > 5 cm in size. Adult patients with T3 or T4 squamous cell carcinoma who received definitive chemoradiation were included. Patients with prior resection were excluded. Higher dose was defined as > than or equal to 5940 Gy. Statistical analyses were performed using logistic regression, Kaplan-Meier, and Cox proportional hazards for overall survival (OS). Results: In total, 1349 patients were analyzed with 412 (30.5%) receiving higher dose radiation therapy (RT). Dose in the higher group ranged from 5940 – 7000 Gy. 5-year OS was 58% and 60% for higher and lower dose RT, respectively. On univariate analysis, higher dose RT (HR 0.998, CI 0.805 - 1.239, p = 0.9887) was not associated with a change in OS but older age (HR 1.484, CI 1.193 - 1.844, p = 0.0004), male sex (HR 1.660, CI 1.355 - 2.033, p < 0.0001), comorbidities (HR 1.496, CI 1.183 - 1.893, p = 0.0008), and long RT (HR 1.248, CI 1.016 - 1.533, p = 0.0347) were significantly associated with decreased OS. The results of multivariate analysis are shown in the Table. Conclusions: There was no observed difference in OS for dose escalation of anal cancers > 5 cm in this population-based analysis, but differences in local control cannot be assessed through the NCDB. Males, elderly, and comorbid patients were particularly high-risk populations with poor chemoradiation survival outcomes. Reducing treatment breaks is important for improving outcomes. Whether dose escalation of large tumors may improve local control and colostomy-free survival remains an important question and is the subject of ongoing trials. [Table: see text]
The impact of chronic kidney disease in locally advanced rectal cancer patients treated with neoadjuvant chemoradiation.
Authors: Dudani Shaan , Marginean Horia , Gotfrit Joanna , Tang Patricia A. , Monzon Jose Gerard , Dennis Kristopher , Kennecke Hagen F. , Powell Erin Diana , Babak Sam , Cheung Winson Y. , Vickers Michael M. ,   On Behalf of the CHORD Consortium
Published: January 2019

794 Background: Chronic kidney disease (CKD) and cancer are common with advancing age. CKD may influence drug tolerance/efficacy and is an independent prognostic factor in some cancers. The impact of CKD on outcomes in patients (pts) with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemoradiation (nCRT) has not been previously studied. Methods: We reviewed pts with LARC undergoing nCRT prior to surgery with curative intent from 2005-2013 across 4 Canadian provinces. Data regarding demographics, staging, baseline renal function, treatments and outcome were collected. CKD was defined as having an estimated glomerular filtration rate (eGFR) (Cockroft-Gault) < 60 ml/min. Primary endpoints were neoadjuvant treatment completion rate, disease-free survival (DFS), and overall survival (OS). Logistic regression and Cox proportional hazard models were used to assess for an association between renal function and outcomes. Results: 1122 (71%) of 1580 pts were included for analysis. Median age was 61 (IQR 54-69), 70% male, 84% performance status 0-1. 28% and 68% had clinical stage II and III disease, respectively. Median eGFR was 93 ml/min (IQR 74-114), with 11% < 60 ml/min (n = 120). 97% of all pts received ≥ 44 Gy (median 50 Gy [range 20-80]). 53% received 5-fluorouracil and 44% received capecitabine as neoadjuvant chemotherapy (nCT). 84% completed nCT, 95% completed neoadjuvant radiotherapy (nRT), and 76% received adjuvant chemotherapy (aCT). Pts with CKD were less likely to receive aCT (62% vs 78%; p < 0.01). There was no significant difference in completion rate of nCT (80% vs 85%; p = 0.15) or nRT (93% vs 95%; p = 0.20) based on renal function. After a median follow up time of 62 months, 8% developed local recurrence, 21% developed distant recurrence and 21% have died. 5-year OS and DFS were 78% and 73%, respectively. Pts with CKD had decreased OS on univariate analysis (HR 1.59, 95% CI 1.11-2.28; p = 0.01), but not on multivariate analysis. DFS was not significantly different based on renal function (HR 1.27, 95% CI 0.89-1.81; p = 0.18). Conclusions: In LARC pts undergoing nCRT, CKD was associated with less use of aCT but did not have any independent association with nCT and nRT completion rate, DFS or OS.
Effect of adjuvant chemotherapy on stage II colon cancer: Analysis of Korean national data.
Authors: KIM Minki , Won Daeyoun , Oh Seong Taek , Lee In Kyu 
Published: January 2019

798 Background: Debates exist regarding the effectiveness of adjuvant chemotherapy for stage II colon cancer. This study aimed to investigate the current status of adjuvant chemotherapy and its impact on survival for Korean stage II colon cancer patients by analyzing the National Quality Assessment data. Methods: A total of 7880 patients who underwent curative resection for stage II colon adenocarcinoma between Jan 2011 and Dec 2014 in Korea were selected randomly as evaluation subjects for the quality assessment. The factors that influenced overall survival were identified. The high-risk group was defined as having at least one of the following: perforation/obstruction, lymph node harvest less than 12, lymphovascular/perineural invasion, positive resection margin, poor differentiation, or pathologic T4 stage. Results: The median follow-up period was 38 (1-63) months. Chemotherapy was a favorable prognostic factor for either the high- (HR 0.50 [0.40-0.62], p < 0.001) or low-risk group (HR 0.74 [0.61-0.89], p = 0.002) in multivariate analysis. This was also the case in patients over 70 years of age. The hazard ratio was significantly increased as the number of involved risk factors was increased in patients who didn’t receive chemotherapy. However, there was no survival difference between low-risk group patients and patients who only had 1 risk factor among patients who received adjuvant chemotherapy (HR 1.19 [0.93-1.52], p = 0.165). Adding oxaliplatin showed no difference in survival (HR 1.36 [0.91-2.03], p = 0.132). Conclusions: Adjuvant chemotherapy can be recommended for stage II colon cancer patients, but the addition of oxaliplatin to the regimen must be selective.