bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between volume of bone irradiated during pelvic radiation therapy (RT) for rectal cancer and complete blood counts (CBC).
Authors: Marina Ovidiu , Ionascu Dan , McAree Daniel P , Schulze Derek , Dekhne Aamod , Wallace Michelle , Grills Inga S. , Ye Hong , Robertson John M. 
Published: February 2017

551 Background: CBCs decrease during standard 3D-conformal pelvic RT for rectal cancer. We evaluated RT plans and CBCs to determine if this decrease is due to RT or only concurrent chemotherapy. Methods: Pelvic bones were contoured for 69 patients who had CT-based treatment plans and CBCs 3 months pre and during RT. CBCs included white blood cells (WBC), hemoglobin (Hgb) and platelets (PLT). The pelvic bones included the bilateral femoral heads and innominate bones, sacrum and L5. Dose volume histograms (DVH) for the pelvic bones were encoded as volumes (Vol) receiving 10 (V10) to 50 Gy (V50) in cc, and percent (Perc) (P10 to P50). The paired t-test was used to compare CBCs pre and during RT. CBCs were analyzed with a repeated measures general linear model for uneven time intervals (R 2.15.1). Results: Median age was 60 y, with 40 men (58%) and preoperative RT in 32 (46%). The median RT dose was 50.4 Gy (range 25.2-60.4 Gy), with all but 2 patients receiving ≥45 Gy. Among 677 CBCs, there were 675 WBC, 677 Hgb, and 672 PLT. The average WBC pre and during RT were 7.7 vs 5.4 bil/L (p<0.001), Hgb 12.9 vs 12.5 g/dL (p=0.005), and PLT 271 vs 227 bil/L (p<0.001). A statistical model with variables for time, the 3-week chemotherapy cycle, the pre-RT average CBC, and 1st and 2nd-order interactions of time with Vol and Perc was constructed. All Vol and Perc for all bones as one structure were significant predictors of the PLT timecourse during RT, with the first-order time-dose interaction encoding a decrease over time, and the second-order time-dose interaction a recovery towards the end of RT. For WBC, V40 and P40 were most predictive (p<0.001), with P40 more so. There were no time-dependent interactions for Hgb. All models had a significant effect of pre RT average CBC and the 3-week chemo cycle. Conclusions: Whereas chemotherapy acts systemically, RT affects a circumscribed area. As such, bone marrow outside the RT field can compensate for lost hematopoiesis over time. Pelvic bone RT dose correlates with PLT and WBC (circulation half-life 1-3 d) but not Hgb (half-life 120 d) supporting an effect of RT in decreased CBC during treatment. Research of approaches that minimize bone marrow dose during pelvic radiotherapy is warranted.
Safety and efficacy during first line with cetuximab in KRAS wild-type metastatic colorectal cancer (mCRC): Results of a large prospective multicenter cohort carried out by the premium French observational study.
Authors: Mineur Laurent , Seni Gilles , Miglianico Laurent , Dourthe louis-Marie , Bonichon Nathalie , Moreau Lionel , Guimbaud Rosine , Smith Denis , Achille Emmanuel , Herve Robert , Bons Jean Michel , Remy Stephane , Daures jean Pierre 
Published: February 2017

555 Background: Cetuximab improves benefit in patients with kras wild type when added to CT for mCRC (Crystal, opus, celim trials). In order to assess the safety and efficacy of cetuximab in daily-practices a national prospective observational multicenter study was performed. Methods: Physicians (n=94), in health institutions (44 public and 46 private hospitals, 4 cancer centers) enrolled prospectively 502 patients. The eligibility criteria were kras wild type mCRC treated with cetuximab in combination with CT as first-line regimen and at least one measurable lesion. Data are available at 3 months, for 496 patients enrolled between september 2009 to march 2012. Results: Mean age 65,7 years old, 62.9% male, ECOG score 0-1 88.1%, 2-3 11.9%, metastases site were liver 70%, lung 26% and others unlimited 39%. Resectable mCCR 10.6%, potentially resectable metastases 33.9% and unresectable 55.5%. Primary tumor location colon: right 20.9%, transverse 6%, left 35.3%, rectum 30.5%, others 7.3%. Primary cancer was resected in 66 % (n=332), 25% (n=125) received adjuvant CT. Cetuximab was administrated respectively every week(20.2%) or two weeks (79.8% of patients). CT regimens were folfiri 51.8%, folfox 4 36.5%, others 11.7%. At 3 months response rate was complete in 4.6%, partial 44.9%, stable 34%, progression disease 16.5%. Reasons for specific cetuximab treatment discontinuation (n=207) were progressive disease 35.3%, therapeutic break 23.2%, all grade cutaneous toxicity and allergic reaction 15.9%, patient request 2.9%, surgery recruitment 20% radiotherapy, radiofrequency and others 2.7%. Adverse events in grade 2 and 3-4 were respectively neutropenia (9.4%;7.9%), anemia (8.5%;1.4%), thrombocytopenia (2.6%;1%), diarrhea (10.8%;5.3%) vomiting (5.3%;2.2%), folliculitis (17.9%;3%), xerosis (13.3%;2%), paronychia (5%;0.9%), allergy 3.4%. Conclusions: Values reported are consistent with those previously identified trials and can better understand the reasons of drug stopping. The study continues to evaluate prognostic factors influencing response, toxicity and drug discontinuation.
Intratumoral gene expression profile of genes involved in 5-FU metabolism and angiogenesis, comparison with tumor invasion depth in patients with advanced gastric cancer.
Authors: Azuma Mizutomo , Naruke Akira , Kim Myungchul , Ishido Kenji , Katada Chikatoshi , Higuchi Katsuhiko , Sasaki Tohru , Tanabe Satoshi , Koizumi Wasaburo 
Published: February 2017

56 Background: The biopsy specimen by endoscopy can only show the surface of its gene profiles. We hypothesis whether the biopsy specimen can reflect all part of gene profile or not. We tested how 5-FU related genes and angiogenesis gene expressed in the invasion depth in the primary tumor of the Stage II or III advanced gastric cancer. Methods: Twenty-five patients with stage II or III advanced gastric cancer who underwent gastrectomy were analyzed.Formalin-fixed, paraffin-embedded tumor tissues were dissected from the surface section (mainly mucosa), the middle section (mainly submucossa) and the deep section (the part invaded most deeply) of the primary tumor and the normal gastric mucosa tissue by the laser-captured microdissection technique and were analyzed for target gene expressions using a quantitative real-time polymerase chain reaction.We analyzed for target genes as TS, TP, DPD, ERCC1, EGFR, VEGF and HIF1α. Results: In the primary tumor, TP and HIF1α gene expression in the surface section was significantly higher than in the deep section (p=0.021, p=0.012). These gene expression and the depth of the primary tumor had a correlation coefficient (TP; r=0.29, HIF1α; r=0.33). There was no significantly difference between surface and deep section in the primary tumor in TS, DPD, ERCC1, VEGF, EGFR except TP and HIF1α. There was no significantly difference between surface and middle section in the primary tumor in all gene expression. There was no significantly difference between middle and deep section in the primary tumor in all gene expression. Conclusions: Only TP and HIF1α had tendency that these gene expression became higher as invaded from the surface section to the deep section of primary tumor. These data suggested that biopsy specimens could be predicted gene expression profile from the surface of gastric cancer. But as you know, gastric cancer has a heterogeneity gene profile. We need at least few samples to say whole gene expression of its tumors. This is preliminary data, it will need further study to proof these result.
Relationship of oral acetaldehyde concentration and oral microflora with the development of superficial pharyngeal or esophageal squamous cell carcinoma.
Authors: Iizuka Toshiro , Kikuchi Daisuke , Hoteya Shu , Tanaka Mamoru , Kaise Mitsuru 
Published: February 2017

57 Background: Acetaldehyde in alcoholic beverages is evidently carcinogenic to the pharynx and esophagus. The relationship between microflora in the gastrointestinal tract and carcinogenesis, such as that between Helicobacter pyloriand gastric cancer, has attracted attention; however, there are few reports of oral microflora influencing the developing the squamous cell carcinoma of the pharynx or esophagus. Therefore, we investigated factors that might influence the development of cancer in the pharynx and esophagus. Methods: A total of 82 patients participated in this study and consisted of 50 with pharyngeal or esophageal cancer treated by endoscopic submucosal dissection and 32 with no cancer. Chromosomal DNA was extracted from bacteria in the oral mucosa, and terminal restriction fragment length polymorphism analysis was carried out. The concentration of acetaldehyde in saliva was measured, and clinical factors were assessed by multivariable analysis. Results: The average values of clinical parameters in patients with pharyngeal or esophageal cancer were as follows: age, 68 years; acetaldehyde, 2.5 μmol/l; GOT, 30.5 IU/l; GPT, 23.5 IU/l; γGTP, 79.4 IU/l; Hb, 14.1 g/dl; MCV, 97.6 fl; alcohol consumption, 6.1 g/day; and Brinkman index, 764. In patients with no cancer, the same parameters were as follows: age, 69 years; acetaldehyde, 4.8 μmol/l; GOT, 23 IU/l; GPT, 21.9 IU/l; γGTP, 36.9 IU/l; Hb, 14.2 g/dl; MCV, 93.7 fl; alcohol consumption, 1.9 g/day, and Brinkman index, 350. Multivariable analysis showed that acetaldehyde concentration (odds ratio: 0.63; 95% CI: 0.47–0.85) and alcohol consumption (odds ratio: 1.64; 95% CI: 1.19–2.25) were significantly different between the two groups. Cluster analysis extracted 16 small clusters from the dendrogram. In 3 clusters among them, the percentage of patients with cancer was more than 80%. Conclusions: Cluster analysis revealed three clusters with a high incidence of cancer patients. Therefore, acetaldehyde concentration and alcohol consumption may be related with carcinogenesis of the pharynx and esophagus. We intend to identify the microbial flora of each cluster in a future study.
Effectiveness of capecitabine plus oxaliplatin for advanced colon cancer: A public hospital experience.
Authors: Luu Carrie , Velasquez Johnathan , Kaji Amy , Stabile Bruce E. , Petrie Beverley A , Kumar Ravin , Caton Amy , Kim Joseph , Chen Steven L. , Lee Byrne 
Published: February 2017

570 Background: Adjuvant chemotherapy has been shown to improve disease-free survival (DFS) and overall survival (OS) in advanced colon cancer (CC). 5-fluorouracil (5-FU)/leucovorin and oxaliplatin is the first line therapy for stage II and III CC. Due to systematic and financial constraints imposed by administering infusional 5-FU, this agent is not available at our institution. Capecitabine plus oxaliplatin (CAPOX) has been studied by others as a possible alternative. We report our experience with CAPOX in the adjuvant treatment of CC patients in a large, public hospital. Methods: A retrospective study of 142 patients with CC who received CAPOX from 2005 to 2011 was performed. Data on patient demographics, treatment, disease recurrence, and survival were analyzed. Survival was assessed by the Kaplan-Meier method. The Cox regression model was used for multivariate analysis. Results: There were 60 female and 82 male patients with a mean age of 54 years (range 21-80). 57 patients were diagnosed with stage II CC and 85 with stage III CC. All patients with stage II and stage III disease underwent curative-intent surgical resection, except for one patient, who refused surgery. 14/141 operations (10%) were performed emergently. Mean follow-up was 36 months (range 2-85 months). The 3-year OS rates were 91% and 81% for stages II and III, respectively. The 3-year DFS rate was 74% for stage II and 66% for stage III. By multivariate analysis, only cancer stage was predictive of overall survival. Conclusions: CAPOX is an effective treatment for stage II and III CC in the adjuvant setting. Our study supports recent evidence demonstrating the efficacy of CAPOX in CC. Ease of administration and improved utilization of resources make it an ideal regimen for public hospital facilities.
Oxaliplatin and capecitabine initially concomitant to radiotherapy then administered in the resting period in high-risk locally advanced rectal cancer.
Authors: Ding Pei-Rong , Gao Yuan-Hong , An Xin , Chen Gong , Wang Feng-Hua , Cai Mu-Yan , Zeng Zhi-Fan , Kong Ling-Heng , Lin Jun-Zhong , Wu Xiaojun , Lu Zhen-Hai , Li Li-Ren , Wan De-Sen , Pan Zhi-Zhong 
Published: February 2017

581 Background: Although neoadjuvant chemoradiotherapy (CRT) has dramatically reduced the risk of local recurrence in locally advanced rectal cancer (LARC), it fails to reduce the risk of systemic failure. To enhance systemic control, we develop an alternative approach, combining intense chemotherapy using Oxaliplatin and Capecitabine (XELOX regimen) concomitant to radiation and extending the chemotherapy regimen to the resting period (consolidation chemotherapy) for high risk LARC. The aim of the present study was to evaluate the efficacy and toxicities of this strategy. Methods: Patients with high risk LARC were treated with CRT. Two cycles of XELOX regimen was administered concomitant to radiation. Then an additional cycle of the same regimen was extended to the resting period one week after completion of chemoradiation. Tumor response, toxicities associated with CRT and consolidation chemotherapy, and surgical complications were recorded. Results: Thirty-six patients with high risk LARC were identified treated with the strategy from 2010 to 2012. All patents completed the planned dose of radiation and concurrent chemotherapy, and two patient was unable to complete the consolidation chemotherapy because of grade 3 toxicities. Grade 3 acute toxicities were 2.8% leucopenia, 2.8% diarrhea, and 2.8% radiation dermatitis. All patients underwent optimal surgery with TME, among whom sphincter-saving procedure was performed in 27 patients (75%). There was no peri-operative mortality in this cohort. Seven patients (19.4%) developed postoperative complications. Complete regression (pCR), major regression (nearly pCR), and moderate or minimal regression were achieved in 13 (36.1%), 16 patients (44.4%), and 7 patients (19.5%), respectively. Conclusions: The preliminary results suggest that XELOX regimen concomitant to radiation and extended to the “resting period” after radiation completion are well tolerated. This strategy is associated with high pCR and nearly pCR rates. The promising results warrant further investigation of the impact of consolidation chemotherapy following CRT for LARC in future clinical trials.
How do first-line treatment and other factors affect the receipt of second-line treatment for elderly metastatic colon cancer patients?
Authors: Zheng Zhiyuan , Onukwugha Ebere , Hanna Nader , Reese Emily S , Seal Brian S. , Mullins C. Daniel 
Published: February 2017

592 Background: Metastatic colon cancer (mCC) patients might receive multiple lines of chemotherapy to improve survival or quality of life. However, factors associated with receipt of 1st and 2nd line treatment (TX) haven’t been fully investigated. Methods: Elderly (65+) SEER-Medicare patients diagnosed with mCC in 2003-2007 were followed until death or 12/31/2009 to examine factors for receipt of 1st and 2nd line TX. A Cox regression framework and inverse probability weighting (IPW) method were used to adjust for patients’ informative (death) and non-informative (dropout or end-of-study) censoring histories. Additionally, we controlled for patients’ 1st line TX in the IPW to determine factors for receipt of 2nd line TX. Results: Of 7,951 mCC patients, 3,266 patients received at least 1 line TX, and 1,440 went on to 2nd line TX. For 1st line TX, significant clinical factors were CCI = 2 (HR = 0.86; p = 0.02), oxygen use (HR = 0.74; p = 0.04), walking aid use (HR = 0.58; p = 0.02), and wheel chair use (HR = 0.50; p < 0.01); significant demographic characteristics were age groups 95+ (HR = 0.11; p < 0.01), 85-94 (HR = 0.24; p < 0.01), 75-84 (HR = 0.70; p < 0.01), as compared to 65+-74, female (HR = 1.12; p < 0.01), married (HR = 1.43; p < 0.01), and African American (AA) (HR = 0.80; p < 0.01); significant factors for socio-economics status were state buy-in status (SBI) (HR = 0.97; p < 0.01), and zip code level household median income (HR = 1.03; p < 0.01). For 2nd line TX, significant factors were hospital bed use (HR = 2.82; p = 0.05), oxygen use (HR = 0.68; p = 0.02), age group 85-94 (HR = 0.718; p = 0.02) as compared to 65+-74, and days delayed for 1stline TX (HR = 0.998; p < 0.01). Conclusions: Various factors were associated with receipt of 1st line TX. Conditional on the receipt of 1st line TX, many factors became insignificant for receipt of 2nd line TX, such as age, female, marriage status, AA, SBI, and zip code level household income. Hospital bed use reduced the probability of receipt of 1st line TX, but increased the probability of receipt of 2nd line TX.
Randomized phase III study of S-1 plus oxaliplatin versus S-1 plus cisplatin for first-line treatment of advanced gastric cancer.
Authors: Higuchi Katsuhiko , Koizumi Wasaburo , Yamada Yasuhide , Nishikawa Kazuhiro , Gotoh Masahiro , Fuse Nozomu , Sugimoto Naotoshi , Nishina Tomohiro , Amagai Kenji , Chin Keisho , Niwa Yasumasa , Negoro Yuji , Imamura Hiroshi , Tsuda Masahiro , Yasui Hirofumi , Fujii Hirofumi , Yamaguchi Kensei , Yasui Hisateru , Hamada Chikuma , Hyodo Ichinosuke 
Published: February 2017

60 Background: S-1 plus cisplatin (SP) is the standard first-line treatment regimen for advanced gastric cancer (AGC) in Japan. S-1 plus oxaliplatin (SOX) for AGC showed promising efficacy and safety outcomes in the previous phase II study. We aimed to evaluate the non-inferiority of SOX to SP for AGC. Methods: Patients (Pts) with unresectable advanced or recurrent gastric cancer were randomly assigned to SOX (oral S-1 40 mg/m2 b.i.d. for 14 days plus oxaliplatin 100 mg/m2 iv on day 1, q3w) or SP (oral S-1 40 mg/m2 b.i.d. for 21 days plus cisplatin 60 mg/m2iv on day 8, q5w). Eligibility criteria included PS 0-2, age 20 years or older, adequate major organ functions. Primary endpoints were non-inferiority in progression-free survival (PFS) as compared with SP and relative efficacy in overall survival among the groups. Main secondary endpoints included response rate (RR), safety, and length of hospital stay (LOS) per cycle. The primary analysis for PFS was planned after 456 PFS events occurred. Results: Six hundred eighty five pts enrolled were randomly assigned to SOX (n=342) or SP (n=343) between Jan. 2010 and Oct. 2011. The evaluable pts for safety and efficacy were 673 (SOX/SP, 335/338) and 642 (SOX/SP, 318/324), respectively. The median PFS was 5.5 months for SOX vs. 5.4 months for SP (hazard ratio [HR] =1.004; 95% confidence interval [CI], 0.840-1.199). The upper limit of the 95% CI for HR was not above the margin of 1.30 and met the predefined criterion for non-inferiority. RR was 55.7% for SOX and 52.2% for SP (P=0.374). Grade 3 or 4 toxicities in SOX v. SP were neutropenia 19.5% v. 41.5%, thrombocytopenia 9.5% v. 10.4%, febrile neutropenia 0.9% v. 6.9%, hyponatremia 7.1% v. 15.2%, sensory neuropathy 4.4% v. 0%, respectively. Serious adverse events were occurred in 29.3 % for SOX and 37.9% for SP. Eight treatment-related deaths were reported in SP (2.4%) and four in SOX (1.2%). The median LOS per cycle was 0.85 day for SOX and 6.00 days for SP (P<0.0001). Conclusions: SOX showed non-inferiority to SP in PFS and the treatment was well tolerated, with benefit in terms of outpatient-based treatment in pts with AGC. SOX is considered as a new standard regimen for the first-line treatment of AGC on an outpatient basis. Clinical trial information: JapicCTI 101021.
Efficacy and safety of trastuzumab (T-mab) and paclitaxel for T-mab naïve patients with HER2 positive previously treated metastatic gastric cancer (JFMC45-1102).
Authors: Miki Akira , Nishikawa Kazuhiro , Noshiro Hirokazu , Tsuburaya Akira , Nishida Yasunori , Yamada Yasuhide , Miwa Hiroto , Sakai Yoshinori , Yoshida Kazuhiro , Kodera Yasuhiro , Boku Narikazu , Morita Satoshi , Sakamoto Junichi , Saji Shigetoyo , Kitagawa Yuko 
Published: February 2017

63 Background: The global, randomized, Phase III ToGA study showed that the first-line treatment of trastuzumab (T-mab) combined with capecitabine and cisplatin a survival (OS) benefit for patients (pts) with HER2-positive metastatic gastric cancer (mGC). However, there is no report concerning about the efficacy and safety of T-mab containing second-line treatment for T-mab naïve patients with HER2-positive mGC. Therefore, we planned a phase II study of paclitaxel plus trastuzumab in this setting. Methods: JFMC45-1102 is multicentre Phase II study. Patient (pts) with HER2 positive (IHC3+ or IHC2+/FISH+), histologically confirmed gastric adenocarcinoma, age≥20, received one or more prior chemotherapy but no prior therapy with T-mab, normal left ventricular ejection fraction (LVEF ≥ 50%) were eligible. Pts received paclitaxel (80 mg/m2on days 1, 8, and, 15 q4w) plus T-mab (8 mg/kg for the initial dose, followed by 6 mg/kg q3w) until disease progression, unacceptable toxicity or patient’s refusal. The primary endpoint was overall response rate evaluated according to RECIST ver1.0 (ORR; Threshold and expected ORR would be 15% and 30%), and the secondary endpoints include progression free survival (PFS), time to treatment failure (TTF), overall survival (OS) and safety. A LVEF assessment was repeated every three months. Results: Between November 2011 to March 2012, 45 pts were enrolled. Pts characteristics were: gender (M/F); 36/9, median age; 69, ECOG PS0/1/2; 34/10/1, advanced/recurrence; 25/20, number of prior treatment (1/2): 40/5. At 16 weeks, 43 pts were ORR and disease control rate (CR+PR+SD) were 37.2% (95% CI; 23.0%-53.3%) and 83.7%(95% CI; 69.3%-93.2%), respectively. The LVEF assessment was performed in 31 patients. More than 10% decrease in LVEF was observed in only one patient, although total incidence of decrease in LVEF was 56% (17/31 pts). Conclusions: Combination chemotherapy of paclitaxel plus trastuzumab is generally well tolerated and showed promising activity for T-mab native patients with HER2-positive previously treated advanced or recurrent gastric cancer. Clinical trial information: UMIN000006223.