bluuebunny/crossref_metadata_2025_split huggingface dataset:
A preoperative clinical staging and metabolic imaging model to predict prognosis in early-stage esophageal adenocarcinoma.
Authors: Turkington Richard Calvin , Blayney Jaine K. , Jalil Awais , Goody Rebecca Barbara , Papafili Anastasia , Henderson Chloe , McManus Damian , Johnston Patrick , Kennedy Richard D. , Eatock Martin McKinlay 
Published: February 2017

63 Background: Accurate prediction of outcome for neo-adjuvant therapy in early stage esophageal adenocarcinoma (EAC) is essential for clinical trial design, patient counseling and treatment decisions. The use of 18F-fluorodeoxyglucose positron emission tomography (PET) has improved the staging of EAC and can predict pathological response and survival. Our aim was to develop a pre-operative prognostic model based on metabolic imaging and clinical parameters. Methods: Between April 2004 and December 2010, 118 patients with early stage adenocarcinoma of the distal esophagus or gastro-esophageal junction were treated with platinum and fluorouracil-based combination chemotherapy prior to surgical resection. Patients were staged by endoscopic ultrasound and PET/CT was performed prior to, and upon completion of, chemotherapy. A metabolic response was defined as a >35% reduction in the maximum standard uptake variable (SUVmax). The final prognostic model was selected by multivariate Cox regression analyses and the concordance-index (c-index) was used to assess the fit of the final multivariate model. Results: In both the univariate and multivariate analysis of patient prognosis post-surgery, five pre-surgery factors were included: clinical T and N staging, PET response, neutrophil-lymphocyte ratio and albumin levels. The majority of the patients were T3 (82.1%) and N1 (73.7%) and 69.8% of patients demonstrated a PET response. In the univariate analysis PET response was the only significant prognostic factor with a median overall survival (OS) of 60.4 months for responders compared to 23.3 months for non-responders (p=0.0241). The final multivariate model of T staging and PET response had a c-index of 0.624 with T3/PET non-response resulting in a poorer prognosis compared to T3/PET response and T2/PET responder or non-responder (median OS 11.5 vs 44.5 vs undefined months; p=0.0284). We seek to validate our model in an independent patient dataset to assess its predictive capability. Conclusions: Metabolic imaging and clinical staging can be combined in a prognostic model in early stage EAC. Our model can inform patient counseling and the development of clinical trial strategies.
Effect of intensity-modulated radiation therapy with SIB technique on local control and toxicity for neoadjuvant pelvic radiation with concurrent 5-fluorouracil based chemotherapy for rectal cancer compared with three-dimensional conformal radiation therapies.
Authors: Thawani Nitika , Shilpa Vyas , Hasan Shaakir , Axelrud Gabriel , Niloyjyoti Deb , Mutyala Subhakar 
Published: February 2017

632 Background: To compare the areas of residual disease after neoadjuvant pelvic radiation with 5-FU based chemotherapy for rectal cancer using Intensity Modulated Radiation Therapy (IMRT) with simultaneous integrated boost (SIB) technique compared to 3D Conformal Radiation Therapy (3DCRT) Methods: Fourty nine (49) consecutive rectal cancer patients treated with pelvic radiation and concurrent 5-FU based chemotherapy were analyzed. We compared twenty-eight (28) patients treated on an institutional IMRT protocol versus twenty-one (21) patients treated with 3DCRT. All patients received 45-50.4 Gy to the pelvis in 3DCRT group. All patients with IMRT received 45 Gy in 25 fractions to the pelvic no des. The primary rectal tumor recieved a simultaneous integrated boost to a dose of 50 Gy in 25 fractions. IMRT planning was done with dose constraints for bladder, rectum, and small bowel and bone marrow. All patients in both groups received 5-FU based chemotherapy during radiation. Evaluation of toxicity was based on RTOG criteria. 2 patients in the 3DCRT group and 2 in IMRT group received either growth factors or blood-products transfusion and needed hospitalization during treatment secondary to acute toxicities. Results: All patients completed their prescribed course of radiation. CR rates were 5/21(23%) in 3DCRT and 4/28(25%) in the IMRT-SIB (p-value 0.74). 9/21(42%) in 3D and 19/29(65%) in the IMRT group underwent Low anterior resection according to the location of the tumor. There was no grade 4 toxicity in the IMRT-SIB group. Overall grade 2 toxicity in 3D Vs IMRT-SIB group was - GI -52% Vs 19%, GU- 8% Vs 8%, skin 42 Vs 4%, hematologic 33 Vs 47%. Overall Grade 1 toxicity in 3DCRT Vs IMRT group was- GI- 33% Vs 52%, GU 23% vs 28%, Skin 52% Vs 38%, hematologic 4% Vs 33%. Conclusions: Neoadjuvant pelvic radiation with 5 FU for rectal cancer has similar local control rates. There is less GI, skin and hematologic toxicity when delivered via IMRT-SIB versus 3DCRT. IMRT is safe and may allow dose escalation with potential probability of increased tumor response.
The correlation of neutrophil/lymphocyte ratio and tumor reduction ratio in preoperative chermoradiotherapy for advanced rectal cancer.
Authors: Yasuda Koji 
Published: February 2017

633 Background: Preoperative chemoradiotherapy (CRT) is widely used for the treatment of advanced lower rectal cancer and is considered to reduce the local recurrence rate and improve the anus preservation rate. However, the tumor reduction effect varies among patients, and thus far, no factor has yet been found to be effective in the prediction of therapeutic efficacy. Recent studies have shown tumor immunity in the tumor microenvironment to be involved in the anti-tumor effect of radiation and anti-cancer drugs. Among these studies, some show that the neutrophil/lymphocyte (NL) ratio in blood test results correlates with the therapeutic efficacy. We examined the correlation between the NL ratio based on blood test results and tumor-reducing effect of preoperative CRT on advanced lower rectal cancers. Methods: We included 30 advanced lower rectal cancer patients who underwent preoperative CRT during the period ranging from January 2008 to June 2013.For advanced lower rectal cancers classified as cT3orT4NXM0, preoperative CRT was conducted according to the following regimen: 50.4 Gy (1.8 Gy × 28 fr) + UFT (300 mg/day, LV [75 mg/day]) × 28 days. The neutrophil count and lymphocyte count were determined based on the blood tests conducted before and after CRT; the NL ratio was calculated, and the correlation between the value of the ratio and tumor reduction rate was examined. Results: Radical surgery was performed on 28 of the 30 patients who underwent preoperative CRT. One of the 28 patients showed local recurrence (rate, 3.6%). In addition, down stage tumors were found in 16 of the 28 patients, and the down stage rate was 57.1%. Significant differences (p < 0.0001) were found between the tumor reduction effect and NL ratio from blood tests before CRT, as well as between the tumor reduction effect and the ratio from blood tests after CRT. Conclusions: The above findings suggest anti-tumor immunity in the tumor microenvironment, particularly that lymphocytes might be involved in the antitumor effectiveness of preoperative CRT in advanced lower rectal cancers. In addition, NL ratio from blood tests could be a predictive factor of the tumor reduction effect.
Analysis of Kohne's prognostic index in KRAS wild-type patients with metastatic colorectal cancer (mCRC) treated with salvage-line cetuximab-based regimen: HGCSG0901.
Authors: Doi Ayako , Yuki Satoshi , Tsuji Yasushi , Sasaki Takahide , Fukushima Hiraku , Hatanaka Kazuteru , Naruse Hirohito , Okuda Hiroyuki , Kusumi Takaya , Fujikawa Koshi , Takahashi Yasuo , Saitoh Soh , Kajiura Shinya , Hosokawa Ayumu , Watanabe Yutaka , Yamamoto Fumiyasu , Kudo Mineo , Akakura Nobuaki , Sakata Yuh , Komatsu Yoshito 
Published: February 2017

634 Background: In the treatment for mCRC, it is essential for understanding the prognosis of each individual patient. Köhne’s index (KI) based on performance status, white blood cell count, alkaline phosphatase and number of metastatic sites has been previously proposed. However, in the salvage setting, the validity of KI has not been reported in patients treated by cetuximab-based chemotherapy. Methods: 269 patients with mCRC treated by cetuximab contained chemotherapy were retrospectively registered from 27 centers in Japan. This analysis was included in the KRAS wild-type patients who were refractory to or intolerant for 5-FU/irinotecan/oxaliplatin and were never administered anti-EGFR-antibody. Univariate and multivariate analysis for overall survival were performed using patient characteristics. Survival analyses were performed with Kaplan-Meier method, log-rank test and Cox proportional hazards model. The analysis was also designed to determine whether the Köhne’s classification could be extended to other endpoints such as progression-free survival. Results: All data were available for prognostic categorization in 127 patients. Median overall and progression-free survival was 9.8 and 4.2 months. The distribution and median survival / progression-free survival for KI were as follows: low risk (L) (n = 40; 13.1/5.1 months), intermediate risk (I) (n = 17; 9.6/3.5 months), and high risk (H) (n = 70; 7.6/4.1 months). For overall survival, there was significant difference between L and H (p = 0.004), but not between L and I (p = 0.213), and between I and H (p = 0.321). For progression-free survival, there was tended to difference between L and H (p = 0.083), but not between L and I (p = 0.392), and between I and H (p = 0.630). In Cox multivariate analysis, KI showed an independent prognostic impact (HR 1.370, p = 0.010), but not predictive impact (HR 1.147, p = 0.212). Conclusions: In this analysis, KI might be a prognostic factor in salvage treatment with cetuximab-based regimen, but no effect predicted impact. Moreover, the prospective evaluation is needed for the further validation.
Timing of adjuvant chemotherapy in stage III colon cancer as a measure of quality: Reasons for noncompliance.
Authors: Rashid Omar M. , Coyne Karen A. , Ross Thomas W. , Shibata David 
Published: February 2017

640 Background: The Institute of Medicine's report on improving cancer care, along with the evolution of ASCO's Quality Oncology Practice Initiative, has helped to develop process measures into critical quality of cancer care indicators. One such measure relates to "receipt of chemotherapy for stage III colon cancer (CC) within 120 days of diagnosis" and is now being incorporated into processes including hospital accreditation (American College of Surgeons; ACS), managed care contracts and Center for Medicare and Medicaid Services (CMS) quality monitoring. To better understand potential pitfalls related to the strict guidelines of this measure, we sought to evaluate institutional adherence at a tertiary care cancer center and to examine the reasons for non-compliance. Methods: A retrospective review was performed of all cases of stage III colon cancer reported at a single institution from 2008 – 2012. Coding for compliance was performed using standard ACS guidelines. Results: A total of 122 eligible cases were identified and consisted of 49 (40.2%) women and 73 (59.8%) men with a median age of 58 (range 32 - 77). Overall, 15 (12.3%) cases were non-compliant with 2 (1.6%) lost to follow up. Of the non-compliant cases, 14 (93.3%) cases did go on to receive chemotherapy while 1 (6.7%) never received adjuvant treatment. Of those receiving delayed treatment, 7 were due to patient-centered factors [e.g. patient timing preference (n=4), request for chemotherapy closer to home (n=2) and lost to follow up (n=1)]. Other reasons included delays at outside facilities (n=4), postoperative complications (n=1) and insurance approval (n=1). In 2 cases, designation of date of diagnosis based on suspicion rather than definitive biopsy contributed to non-compliant status. Conclusions: Our center averaged an annual compliance with the CC adjuvant therapy measure of approximately 90%. Larger scale studies are indicated to determine whether refinements in coding guides that account for patient preferences, clear diagnosis dates and cross-facility care could better reflect quality of care, and also promote improved patient-centered multidisciplinary management.
Panitumumab or cetuximab combined with irinotecan in patients with KRAS wild-type metastatic colorectal cancer previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based regimens.
Authors: Ikezawa Nobuaki , Iwasa Satoru , Shoji Hirokazu , Honma Yoshitaka , Takashima Atsuo , Okita Natsuko T. , Kato Ken , Shimada Yasuhiro 
Published: February 2017

642 Background: Panitumumab and cetuximab are known to be effective in KRAS wild-type metastatic colorectal cancer (mCRC). However, it is not clear whether panitumumab and irinotecan confers benefit that are comparable to those of cetuximab and irinotecan in patients with KRAS wild-type mCRC previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based regimes. Methods: We analyzed 139 patients who had received panitumumab or cetuximabu combined with irinotecan for KRAS wild-type mCRC previously treated with fluor opyrimidine-, oxaliplatin-, and irinotecan-based regimes.We evaluated and compared efficacy and safety of panitumumab plus irinotecan and cetuximab plus irinotecan. Results: Baseline characteristics were similar for the two groups receving cetuximab pulus irinotecan (n = 97) and panitumumab plus irinotecan (n = 42),respectively.In patients with measurable lesions,the response rate (unconfirmed complete or partial response) were 20% (18/92) in the group receving cetuximab plus irintecan and 34% (14/41) in that receving panitumumab plus irinotecan. Median progression-free survival was 5.7 months in the cetuximab plus irinotecan group versus 4.3 months in the panitumumab plus irinotecan group. Median overall survival was 11.2 months in the cetuximab plus irinotecan group versus 13.6 months in the panitumumab plus irinotecan group. The most common adverse events in the cetuximab plus irinotecan versus panitumumab plus irinotecan groups were all-grade rash acneiform (82% versus 90%), paronychia (61% versus 52%), and grade 3-4 neutropenia (26% versus 19%). Conclusions: Panitumumab or cetuximab plus irinotecan were well tolerated and produced similar response rate and survivals compared to those previous clinical traials.These combinations are cosidered as standard treatment in patients with KRAS wild-type mCRC previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based regimes.
Efficacy and safety of FOLFOX biweekly cetuximab as first-line therapy for patients with nonresectable metastatic colorectal cancer (CELINE trial): Multicenter phase II trial.
Authors: Kondo Ken , Kotake Masanori , Doden Kenji , Munemoto Yoshinori , Kobayashi Kenji , Nishimura Genichi , Omote Kazuhiko , Sakamoto Junichi 
Published: February 2017

645 Background: Efficacy and safety of FOLFOX{Bi-weekly cetuximab as first-line therapy for patients with nonresectable metastatic colorectal cancer (mCRC) were examined. Methods: The multicentre phase II trial had began from September 2011. Inclusion criteria were an age of 20 years or older, adenocarcinoma of the colon or rectum, first occurrence of metastatic disease with KRAS wild type tumor that could not be resected, performance status score (ECOG) of 1 or less, and adequate hematologic, hepatic, and renal function. Patients received mFOLFOX6/Cetuximab 500 mg/‡u/biweekly 120min until PD, unacceptable adverse effects, or withdrawal of consent occurred. In the event of grade 2 adverse effects, suspension of Oxaliplatin only was permitted. Primary endpoint was Response Rate, secondary endpoint was anti-tumor effect at week 8, PFS, OS, safety, and efficacy of 5-FU{LV{Cetuximab therapy. Results: 60 patients were screened and 59 underwent the treatment by March 2013. Age 64.5 (38-82), male/female: 47/13, PS 0/1: 51/9, rectal/colon: 31/29 and metastasis in liver/lung/ lymph node/ the other: 51/15/19/7. Data had been analyzed to date showed high response rate, 64% with disese control in 96% -PR 38pts (64%), SD 19 pts (32%). Incident rate of grade 3 or 4 adverse events were neuropenia 19%, peripheral sensory neuropathy 4.8% and rash 8.1%. Conclusions: FOLFOX{Bi-weekly cetuximab therapy benefited in safety administration with high response rate. Therefore it can be considered as a beneficial treatment. Clinical trial information: UMIN000006402.
A retrospective analysis of the demographic profile and clinical outcomes of stage III colon cancer patients treated with adjuvant chemotherapy in a real-world perspective.
Authors: Ramakrishnan Geethakumari Praveen , Pomerantz Sherry , Leighton John Charles 
Published: February 2017

648 Background: It is standard to use results of randomized controlled trials (RCT’s) for therapeutic decisions in community oncology. However participant selection in trial environments may not reflect real-world scenario. We aim to perform a retrospective analysis of patient profile and treatment outcomes in a community cancer center. Methods: Patients with stage III colon cancer offered adjuvant chemotherapy after curative resection from 2003-2010 (N=177) were reviewed. Eighty-seven patients with complete medical records were analyzed. Patient eligibility was assessed on criteria from the MOSAIC and NSABP C-07 trials. Eligible and ineligible patients were compared using Fisher’s exact test, Student’s t-test and Kaplan-Meier survival analysis. Results: The study group (females: 53%) with mean age of 65 years, was predominantly African American (60%). ECOG performance status was ≥ 2 in 13% patients. Only 29% satisfied all standard eligibility criteria. Ineligibility characteristics included age > 75 years (21%), non-malignant severe systemic disease (10%) and > 42 days from surgery to chemotherapy (39%). Seventy-five patients (86%) received chemotherapy. Chemotherapy regimens included FOLFOX (51%), FLOX (10%), FL (29%) and Capecitabine (8%). Total planned dose had to be modified in 64% patients with mean doses of 89% 5-fluorouracil and 79% oxaliplatin employed. The 3-year disease free survival (DFS) was 53% and 5-year overall survival (OS) was 56%. Age ≥ 69 years was significantly associated with poor 3-year DFS (P=0.013). On Kaplan-Meier survival analysis, the ineligible patient group had significantly reduced overall survival (hazard ratio, 2.88; 95% CI, 1.05-4.82; P= 0.037). Conclusions: This pilot venture studied adjuvant management of Stage III colon cancer in a real-world setting. Our results reveal that over 70% patients did not meet standard eligibility criteria and show decreased 5-year OS among these patients that needs to be addressed in future prospective RCT’s.
Survivin expression in circulating tumor cells of patients with gastric cancer.
Authors: Terashima Masanori , Hatakeyama Keiichi , Yamakawa Yushi , Sugisawa Norihiko , Miki Yuichiro , Makuuchi Rie , Goto Hironobu , Tokunaga Masanori , Tanizawa Yutaka , Bando Etsuro , Kawamura Taiichi , Oshima Keiichi , Mochizuki Toru 
Published: February 2017

65 Background: Detection of circulating tumor cells (CTC) in peripheral blood is thought to be a promising method to evaluate the extent of minimal residual disease that may be useful for predicting recurrence and for monitoring treatment efficacy. However, unlike breast or lung cancer, little information is available in patients with gastric cancer. Among them, evaluation of survivin, a member of the inhibitor of apoptosis (IAP) family, mRNA expression in peripheral blood appears to be a promising procedure with relative good performance for predicting recurrence after curative resection. In order to evaluate the clinical significance of surviving expression in peripheral blood, we performed real-time RT-PCR analysis using whole blood obtained from patients with gastric cancer. Methods: A total of 95 patients with gastric cancer treated at our cancer center between Nov. 2009 and Aug. 2012 were enrolled in this study. Peripheral blood samples were collected using PAX gene and RNA was isolated using Boom method. After cDNA synthesis, quantitative real-time PCR targeting survivin gene was performed. The relative expression level of survivin mRNA was calculated with actin beta as an internal standard. Correlation between survivin expression and clinicopathologic factors was investigated. Results: Survivin mRNA expression level in peripheral blood ranged from 34.8 to 1889.6, and the median level was 370.3. Survivin mRNA level tended to be higher in patients with T4, N3b, CY1, and Stage IV. There was no significant correlation with histological type, lympho-vascular invasion, or macroscopic type. If we set a cut-off value at 540, survivin was positive in 27 patients (28%). Disease-free survival was significantly worse in survivin positive patients than in negative patients (p=0.0216). Conclusions: Survivin expression in CTC was higher in advanced stage and appears to be a good prognostic marker in patients with gastric cancer. Validation with large sample size should be performed to confirm the significance of survivin in CTC.
Advantage of adjuvant radiation therapy in octogenarians undergoing surgical resection of rectal cancer.
Authors: Chauhan Dhaval , Burnett Atuhani S. , Rajab Taufiek Konrad , Cevasco Marisa , Ernst Philip , McCain Donald A. , Mokashi Suyog A. 
Published: February 2017

650 Background: Radiation in patients with rectal cancer is an important adjuvant therapy. It can be given either pre-operative or post-operative phase or both. However the optimum timing of the radiation in terms of pre-operative or post-op phase remains a question of debate in octogenarian patients as there is lack of enough evidence. Methods: In this study we aim to find the optimum time of radiation therapy in octogenarians with rectal cancer undergoing surgical resection. Octogenarians with rectal cancer were selected from surveillance, Epidemiology and End Results (SEER) database collected between 1998 and 2009. The data set contained 4,026 patients with rectal cancer who underwent surgical resection and radiation therapy. They were divided into 3 groups. 1,586 (39%) patients had radiation before the surgery. 66 (2%) patients had radiation before and after the surgery, also called the combination group. 2,347(59%) patients had radiation after the surgery. Taking in the consideration of unequal sample sizes, Tukey-Kramer multiple comparison tests was used to compare the mean survival of the patients in each group. Results: The mean survival in pre-operative radiation group was 37.7 months, in combination group was 48.41 months and post-operative radiation group was 44.3 months. There was no statistically significant difference in survival time between the combination group and the radiation after surgery group (p-value=0.64). There was marginal statistical significance in survival time between the combination group and the before surgery group (p-value=.05). There was a statistically significant difference in survival time between the radiation after surgery group and the radiation before surgery group (p-value<0.0001). Conclusions: Octogenarian patients with rectal cancer undergoing adjuvant radiation therapy, with or without neoadjuvant radiation, have greater survival than compared to neoadjuvant only radiation. There appears to be survival advantage of postoperative radiation therapy in octogenarian patients with rectal cancer.