bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical significance of genetic variations in the PI3K/PTEN/AKT/mTOR pathway in Korean patients with colorectal cancer.
Authors: Lee S. J. , Kim J. G. , Chae Y. S. , Kang B. W. , Jeon S. W. , Park J. S. , Park J. Y. , Choi G. S. , Lee Y. J. 
Published: February 2017

628 Background: Signaling through the PI3K/PTEN/AKT/mTOR pathway is responsible for balancing cell survival and apoptosis. Accordingly, the present study analyzed 14 SNPs of the PI3K/PTEN/AKT/mTOR pathway genes and their impact on the prognosis for patients with colorectal cancer. Methods: Four hundred and forty-four consecutive patients with surgically resected colorectal adenocarcinoma were enrolled in the present study. The genomic DNA was extracted from fresh colorectal tissue and 14 polymorphisms of the PI3K/PTEN/AKT/mTOR pathway genes determined using a real-time PCR genotyping assay. Results: Pathologic stages after surgery were as follows: stage 0/I (n=85, 19.1%), stage II (n=149, 33.6%), stage III (n=147, 33.1%), and stage IV (n=63, 14.2%). Univariate and multivariate survival analysis including stage, age, site of disease, adjuvant chemotherapy, and CEA level showed that these polymorphisms were not associated with progression-free or overall survival. For the clinicopathologic parameters, CEA level and TNM stage were significant prognostic factors in a Cox model for survival. Conclusions: None of the 14 SNPs of the PI3K/PTEN/AKT/mTOR pathway genes investigated in this study was found to be an independent prognostic marker for Korean patients with surgically resected colorectal cancer. No significant financial relationships to disclose.
The role of the KRAS G13D mutation in patients with metastatic colorectal cancer (mCRC) treated with first-line chemotherapy plus cetuximab.
Authors: Tejpar S. , Bokemeyer C. , Celik I. , Schlichting M. , Van Cutsem E. 
Published: February 2017

630 Background: The CRYSTAL and OPUS studies showed that adding cetuximab (cet) to first-line chemotherapy (CT) significantly improved clinical benefit in patients (pts) with KRAS wild-type (wt) mCRC. Pts with KRAS codon 12 or 13 mutations are excluded from cet treatment. Studies suggest that not all KRAS mutations are equivalent in their biologic effects. Occasional responses and prolonged disease stabilization have been recorded following cet treatment of tumors with mainly KRAS codon 13 mutations. We investigated the influence of the most common KRAS codon 13 mutation (G13D) on clinical outcome compared with pts with other KRAS mutations or wt tumors in the CRYSTAL and OPUS trials. Methods: KRAS mutations were detected in tumor DNA from archival material using a PCR clamping and melting curve technique. Treatment arms were compared by KRAS mutation status for progression-free (PFS) and overall survival (OS). Results: In the CRYSTAL study of 1,063 evaluable pts 63% were KRAS wt, 6% were G13D mutant (mt) and 32% had other mutations. In the OPUS study of 315 evaluable pts, 57% were KRAS wt, 7% were G13D mt, and 36% had other mutations. Compared with KRAS wt pts those with G13D mutations did not benefit from the addition of cet to CT (Table). Data of comparisons of the G13D mutation with other KRAS mutations in these studies will be presented. Conclusions: Patients with KRAS G13D mt tumors did not appear to benefit from the addition of cet to first-line CT for mCRC. This analysis confirms the current practice of KRAS mutation testing as the standard diagnostic tool for determining first-line treatment of mCRC pts. [Table: see text] [Table: see text]
Long-term outcome of almost 3,000 patients with carcinoma of the esophagus: Evaluation of the new UICC/AJCC staging system.
Authors: Gertler R. , Schuster T. , Feith M. 
Published: February 2017

64 Background: In the new 7th edition of the TNM classification for cancers of the esophagus, the UICC stage groups are still based on the anatomic extent of the tumor alone. In contrast, the AJCC prognostic groupings is the first staging system for esophageal cancer to add histologic tumor type, tumor site and grade. Methods: Data of a single center cohort of 2,920 patients operated for cancers of the esophagus were analyzed. Statistical methods to evaluate survival of the patients and the prognostic performance of the new staging systems included Kaplan-Meier analyzes and time dependent ROC-analysis. Results: UICC stage, R-status, histologic tumor type and age were identified as independent prognostic factors for cancers of the esophagus. Grade and tumor site, additional parameters in the new AJCC prognostic groupings, were not significantly correlated with survival. Patients with esophageal adenocarcinoma had a significantly better long-term prognosis after resection than patients with squamous cell carcinoma (p < 0.0001). The new number-dependent N- classification proved superior to the former site-dependent classification with significantly decreasing prognosis with increasing number of lymph node metastases (p < 0.001). The new subclassification of T1 tumors also revealed significant differences in prognosis between pT1a and pT1b patients (p < 0.001). However, the multiple new UICC and AJCC subgroupings did not prove distinctive for survival between stages IIA and IIB, IIIA and IIIB, and between IIIC and IV. Conclusions: The new 7th edition of the TNM classification improved the predictive ability for cancers of the esophagus, however, stage groups could be condensed to a clinically relevant number. Differences in patient characteristics, pathogenesis and especially survival clearly identify adenocarcinomas and squamous cell carcinoma of the esophagus as two separate tumor entities requiring differentiated therapeutic concepts. No significant financial relationships to disclose.
Evaluation of the seventh TNM classification system in patients with esophageal cancer receiving chemoradiotherapy.
Authors: Nomura M. , Kodaira T. , Mizota A. , Kondoh C. , Shitara K. , Yokota T. , Takahari D. , Ura T. , Hatooka S. , Muro K. 
Published: February 2017

83 Background: The new 7th edition of the TNM classification system is based on pathologic data of esophageal cancer underwent surgery alone. No report is available on the prognostic evaluation of the new staging system in patients treated with chemoradiotherapy (CRT). The objective of this study was to evaluate the prognostic impact of the 7th edition of the TNM staging system in esophageal cancer patients treated with CRT. Methods: A retrospective review was performed of 301 consecutive patients who met the following inclusion criteria: (1) squamous cell carcinoma of thoracic esophagus; (2) total radiation dose ≥ 50 Gy; (3) concomitant chemotherapy consisting of 5-fluolouracil and platinum; (4) no previous thoracic radiotherapy or surgery. We compared the prognostic impact of the 6th and 7th editions of the TNM staging systems. Also, we compared the prognostic impact of stage group and prognostic group, which was newly defined in the 7th edition. Survival analysis was performed by using log-rank and Cox regression testing. Results: Patients with stage I/II/III/IV were 52/42/54/153 and 57/46/128/70 according to 6th and 7th edition, respectively. Eighty-four patients were shifted to a lower stage in 7th edition compared with 6th edition, and most of these were from stage IV to III (n = 74). There were significant differences among stages I to III (p < 0.01, respectively) according to each edition. However, 7th edition poorly distinguishes between stages III and IV (p = 0.43). The survival curve of stage IV (lymph) almost completely overlapped with stage III (p = 0.69), although there were significant differences between stages IV (lymph) and IV (organ) (p = 0.04). Among the factors included in prognostic group in 7th edition, the histological grade and cancer site had no significant influence on patient survival, and T factor was only independent prognostic factors in multivariate analysis (p < 0.01). Conclusions: Our study suggested several pitfalls in 7th TNM classification as prognostic factor in patients who received CRT. No significant financial relationships to disclose.
Phase II study of weekly low-dose everolimus plus weekly 24-hour infusions of cisplatin and high-dose 5-fluorouracil and leucovorin for first-line treatment in patients with advanced gastric cancers.
Authors: Yeh K. , Shen Y. , Li C. , Yen C. , Hsu C. , Lin Z. , Chen L. , Su W. , Chao Y. , Cheng A. 
Published: February 2017

86 Background: Cisplatin-HDFL, consisting of weekly 24-hour infusions of cisplatin and high-dose 5-fluorouracil (5-FU) and leucovorin (LV), is an effective and low-toxicity regimen for patients with advanced gastric cancer (GC) in Taiwan (J Clin Oncol. 1994;12(4):875; J Clin Oncol. 2006;24(18S):A14063). Everolimus (RAD001), a derivative of rapamycin, is an orally bioavailable mTOR inhibitor. We have demonstrated that low-dose everolimus (0.5-5.0 nM) sensitizes cytotoxic effects of cisplatin and 5-FU in GC cells (Proc Am Assoc Cancer Res. 2007;48:A4043). Methods: Patients who had pathologically confirmed chemonaive advanced GC, at least 1 measurable lesion, a fasting serum triglyceride level > 70 mg/dl, ECOG PS 0-2, and adequate organ functions were treated with everolimus 10 mg po on days 1, 8, and 15 concurrently with the initiation of chemotherapy; cisplatin 35 mg/m2 iv 24h infusion on days 1 and 8; 5-FU 2,000 mg/m2 and LV 300 mg/m2 (HDFL) iv 24h infusion on days 1, 8, and 15, in a every 28-day cycle. Response assessment was performed every 2 cycles. The primary endpoint was confirmed objective response rate (RR) by RECIST. Results: Between March 2008 and July 2010, 24 patients (M:11, F:13) with a median age of 53 (range: 33-69) were evaluable for response. The overall RR was 50% (95% CI: 29-71%) with 12 partial responders. Among a total of 162 cycles (median: 7, range: 1-13) given, grade (Gr) 3/4 toxicities included neutropenia (4.3%), infection (2.5%), nausea (3.1%) and vomiting (3.1%). Gr 1/2 nausea, vomiting, stomatitis, and diarrhea developed in 19.2%, 15.4%, 14.8%, and 5.5% of cycles, respectively. Skin rash and hand-foot syndrome were mild. One patient developed reversible HDFL-related hyperammonemic encephalopathy. Median progression-free survival was 8.4 months (range: 1.3-15.4+) and median overall survival was 14.8 months (range: 4.0-21.6+). Conclusions: Weekly low-dose everolimus plus weekly cisplatin-HDFL is an effective first-line regimen for patients with advanced GC. Addition of weekly low-dose everolimus to infusional cisplatin-HDFL did not add gastrointestinal toxicities. No significant financial relationships to disclose.
A phase II, open-label, multicenter, prospective study of paclitaxel plus capecitabine with subsequent capecitabine maintenance therapy as first-line treatment for metastatic or recurrent gastric cancer.
Authors: Shen L. , Gong J. , Zhang X. , Hu B. , Zhang F. , Zhang J. , Xu N. , Fan Q. , Bai Y. , Jiao S. 
Published: February 2017

98 Background: Paclitaxel has been shown to be effective in AGC. We assess the efficacy and safety of PX-X therapy as first-line treatment for metastatic or recurrent GC in a phase II, multicenter, prospective study. Methods: Patients with previously untreated gastric adenocarcinoma, signed informed consent, target lesion(s), KPS ≥ 70 and adequate organ functions are eligible. Paclitaxel was given as 80 mg/m2 by 3-hour infusion day 1,8, capecitabine 1,000 mg/m2, BID, D1-14, Q3W. Cycles were repeated until progression or maximum 6 or AEs. Then the patients without progression began the second stage treatment as X with same dose/schedule until progression or AEs. PFS, RR, DCR, OS and AEs are the end points evaluated in this study. Results: From 12/2006 to 4/2010, 195 patients (ITT) were enrolled in 21 centers, 1 patient was withdraw due to allergy to paclitaxel, 194 cases were PP. After median follow up of 16.2 months, 16 cases lost. In ITT, 119 pts progressed, 104 pts died. Mean cycles the patients completed was 5. CR and PR were achieved in 1.0% (2 pts) and 32.3% (63 pts) of pts (RR 33.3%), 75 pts had SD (38.5%), 25 pts (12.8%) progressed. PFS of ITT is 208 d (95% CI: 169.1-246.8) and estimated OS is 456 d (95%CI: 286.9-624.2). 45 pts continued to X after PX with good tolerance, median cycles accepted was 4, and OS was longer than 590 d. 23 patients accepted surgery after chemotherapy; the survival data have not been reached. After disease progression, 61 cases accepted second-line treatment, including oxaplatin/irinotecan-based chemotherapy, target therapy, and local therapy. AEs were mild and the grade 3/4 toxicities were leucopenia (13.8%), alopecia(13.3%), neutropenia (8.2%), fatigue (6.7%), nausea/vomiting (5.1%), HFS (5.1%), diarrhea(3.6%), neurotoxicity (3.1%), hepatic dysfuction (2.6%), and anaphylactic shock (0.5%). No treatment- related deaths were recorded in all patients. Conclusions: PX-X as first-line treatment was promising in advanced gastric cancer. Further evaluation of this combination therapy is being carried on phase III clinical trial of ML22697. No significant financial relationships to disclose.
PSA response and early PSA progression evaluated in patients randomized in a phase III trial comparing androgen-deprivation therapy (ADT) plus docetaxel versus ADT alone in hormone-naive metastatic prostate cancer (GETUG-AFU 15/0403).
Authors: Gravis G. , Fizazi K. , Joly F. , Oudard S. , Priou F. , Latorzeff I. , Delva R. , Esterni B. , Habibian M. , Soulie M. 
Published: February 2017

10 Background: Androgen deprivation therapy (ADT) is the standard treatment of hormone naïve metastatic prostate cancer (HNMPC). We initiated a phase III multicentre trial comparing ADT with or without docetaxel (D) in HNMPC (GETUG 15) and the primary endpoint is overall survival. PSA progression defined as an increase of 25% over baseline or nadirin the first 7 months was recently shown to be a strong predictor of death in HNMPC (Hussain M et al J Clin Oncol 27: 2009). Methods: Patients (pts) with HNMPC were randomly assigned to either arm A (ADT plus D: 75mg/m2 q3w, 9 cycles) or arm B (ADT). From 10/2004 to 12/2008, 385 pts were accrued. The median baseline PSA values were 29.4 ng/mL (0.05-2,170) in arm A and 25.3 ng/mL (0.1-11,900) in arm B. Data on PSA response are available in 171/192 pts (arm A) pts and 181/193 pts (arm B) at 3 months and 156 pts (arm A) and 148 pts (arm B) at 6 months. Results: A PSA response (> 30%) was achieved at 3 months in 93.6% (arm A) and 85.1% (arm B; p=0.02). A PSA response (> 50%) was achieved at 3 months in 90.6% (arm A) versus 80.1% (arm B; p=0.01). When assessed at 6 months, a PSA response (> 30%) was obtained in 94.9% (arm A) versus 86.5% (arm B; p=0.02). A PSA response (> 50%) was achieved in 94.9% (arm A) versus 85.8% (arm B; p=0.01) A PSA progression (25% increase) was observed in 1.3% in arm A and 10.1% in arm B (p=0.002). Conclusions: The addition of 3-weekly docetaxel to ADT significantly improves PSA response and significantly reduces PSA progression at 6 months in patients with HNMPC. No significant financial relationships to disclose.
Intensity-modulated radiation therapy (IMRT) for prostate cancer: Toxicity and biochemical control in 183 Chinese patients from a single institution in Hong Kong.
Authors: Poon D. M. 
Published: February 2017

101 Background: To report the biochemical outcome and the acute and late toxicities in 183 Chinese patients with clinically localized prostate cancer treated with IMRT. Methods: Between May 2001 and November 2009, 183 patients with clinically localized prostate cancer were treated with IMRT at the Prince of Wales Hospital. Median follow-up was 44 months (range 8.5 to 112 months).Treatment was planned using an inverse-planning approach, and the beams were delivered by dynamic multileaf collimation. Four-field box technique was used for pelvic irradiation (pelvic RT) if indicated in phase I and IMRT was used for prostate boost in phase II. The median age of the patients was 71.4 (range 45 to 82). According to the NCCN risk classification, 18 (9.8%), 47 (25.7%) and 118 (64.5%) patients belong to favorable, intermediate, and unfavorable risk group respectively. The median prescription dose of the planning target volume of the prostate gland (PTV-G) is 72Gy (range from 66 to 76Gy). 77 patients (42.1%) received pelvic RT. 129 patients (70%) received neoadjuvant hormone and 106 patients (57.9%) received adjuvant hormone. Acute and late toxicities were scored according to the Common Terminology Criteria for Adverse Events Version 4.02. Biochemical failure was defined according to the Houston definition (absolute PSA nadir plus 2ng/ml dated at the call). Results: The 5-year actuarial biochemical-failure free survival for patients in favorable, intermediate and unfavorable risk groups were 95%, 80%, and 83% respectively. 3 patients (1.6%) experienced grade 3 acute gastrointestinal (GI) toxicity. There were no grade 3 acute genitourinary (GU) toxicity. There was no grade 4 acute GI or GU toxicity. 14 patients (7.7%) developed grade 2 late GI toxicity and 8 patients (4.4%) developed grade 3 late GI toxicity. 5 patients (2.7%) developed grade 2 late GU toxicity and 5 patients (2.7%) developed grade 3 late GU toxicity. There was no grade 4 late GI or GU toxicity. Conclusions: These data demonstrate that IMRT for prostate cancer is feasible and safe in Chinese population. The early biochemical outcome is encouraging and the grade 3 late GI and GU complications were below 5%. No significant financial relationships to disclose.
High-grade prostate cancer with favorable results in the modern era.
Authors: Ramahi E. , Swanson G. P. , Du F. , Basler J. 
Published: February 2017

107 Background: Historically, patients with high-grade prostate cancer have the worst outcomes. With the advent of prostate- specific antigen (PSA) screening, diagnosing prostate cancer no longer depends on palpation of a bulky mass on digital rectal exam and prostate cancers are found at an earlier stage. Our aim is to determine the outcome of a modern cohort of high grade patients with the available treatment options. Methods: We reviewed the STVHS Tumor Registry and identified those patients diagnosed with prostate cancer between 2002 and 2008 capturing those patients with Gleason score >7 on biopsy. Details including all recorded PSA values, biopsy and surgical pathology results, primary, neoadjuvant and adjuvant treatment, as well as response to treatment were recorded and analyzed using Kaplan-Meier estimates, log-rank test, and multivariate analysis using Cox proportional hazards models. Results: We identified 297 patients with Gleason 8–10 cancer with a median follow up of 35 months. Initial treatment was surgery in 136, radiation in 52, and androgen ablation in 110; one patient has both surgery and androgen ablation. Five and 10 year biochemical-free survival (BFS), metastasis-free survival, and overall survival are shown in the Table . Overall, 5 year biochemical failure-free survival was 50% and metastasis free survival was 89%, resulting in an overall survival of 77%. Conclusions: Historically, patients with a Gleason score of 8–10 have done very poorly. However, in the modern era, regardless of the initial treatment, the outcome is not as dire. Possible reasons are less bulky tumors or other facets of stage migration. While there is room for improvement, we should not have a nihilistic impression of how these patients will respond to treatment. [Table: see text] No significant financial relationships to disclose.
Long-term results of salvage cryotherapy for prostate cancer.
Authors: Williams A. , Martinez C. , Chalasani V. , Lu C. , Ng C. , Pautler S. E. , Chin J. 
Published: February 2017

108 Background: The optimum treatment of Prostate cancer recurrence following external bean radiation therapy (EBRT) remains a controversial topic. The primary problem with comparing salvage techniques following EBRT is the lack of long term data. We reviewed the long- term overall survival, disease-specific survival and disease free survival of patients who have undergone salvage cryotherapy to the prostate gland. Methods: A retrospective analysis was performed on all patients undergoing salvage cryotherapy for locally recurrent prostate cancer after EBRT by a single surgeon at a single institution from 1995-2004. Patients preoperative, perioperative and postoperative data was reviewed and recorded. Should a patient no longer be followed by the urology service the Patients and the patient's primary care physician or urologist were contacted. Mortality data, PSA results, bone scan results and any details of hormone therapy were recorded for this study. Results: 187 patients were included in the current study from which 176 patients had records available for follow up giving a follow up rate of 94%. Mean follow up was 7.46 years (1-14 years). 52 patients were followed for greater than 10 years. Average time to prostate cancer recurrence in patients who developed recurred was 2.3 years and average time to hormone therapy in these patients was 2.8 years. Overall survival at 10 years was high at 87%. Risk factors for recurrence of tumour identified were presalvage PSA, preradiation and presalvage gleason score. Preradiation gleason score had little impact on survival. PSA nadir of >1.0ng/mL was highly predictive of early recurrence. Disease-free survival rates of between 39 and 64% depending on risk factors. Conclusions: Cryotherapy has a definite role in the management of prostate cancer, representing a minimally invasive salvage treatment with acceptable 10 year disease free survival (DFS) of upwards of 39% and specific groups attaining 10 year DFS of 64%. Presalvage PSA and Gleason score are the best predictors of disease recurrence, whilst preradiation gleason score did not correlate with risk of disease recurrence. A PSA Nadir greater than 1 ng/mL indicates a poor prognosis in which early ADT should be strongly considered. No significant financial relationships to disclose.
A novel repeat biopsy nomogram based on three-dimensional extended biopsy.
Authors: Sakura M. , Kawakami S. , Ishioka J. , Fujii Y. , Numao N. , Saito K. , Koga F. , Masuda H. , Fukui I. , Kihara K. 
Published: February 2017

111 Background: There is no perfect cohort in which nomograms are developed because no biopsy method can detect all cancers. To minimize this inherent verification bias, having a cohort with fewer false negative cases is advantageous. Based on a cohort examined with three-dimensional (3D) extended biopsy protocol, we developed a novel nomogram for diagnosis of prostate cancer on repeat biopsy. Methods: Of 4,074 consecutive male patients undergoing prostate biopsy at our institutions between 2000 and 2009, 775 men with at least one previous negative biopsy underwent repeat biopsy with 3D protocol. Men with previous atypical glands or atypical small acinar proliferation and/or without available prostate-specific antigen (PSA) kinetics information were excluded. The remaining 515 men constituted the study cohort. We developed a logistic regression-based nomogram with 70% of the cohort selected randomly; we validated it with the remaining 30%. Predictive accuracy and performance characteristics were assessed using the area under the receiver operating characteristic curve (AUC) and calibration plots, respectively. The threshold probability was evaluated with decision curve analysis. Results: We developed a novel repeat biopsy nomogram incorporating age, free to total PSA ratio, prostate volume, history of previous extended biopsy, and PSA doubling time. Validation confirmed predictive accuracy with an AUC value of 0.791. Calibration plots showed good agreement. The decision curve of the nomogram was superior to the decision curve of biopsying all men in a range of threshold probability over 0.15. At the threshold of 0.2, the number of unnecessary biopsies could be reduced by 10 per 100, without missing PCa. Conclusions: We developed a novel repeat biopsy nomogram based on a cohort examined with 3D extended biopsy. This repeat biopsy nomogram is clinically beneficial, saving a substantial number of unnecessary biopsies. No significant financial relationships to disclose.