bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel staging system for disease-specific survival in patients with breast cancer treated with surgery as the first intervention.
Authors: Yi M. , Mittendorf E. A. , Buchholz T. A. , Sahin A. A. , Kuerer H. M. , Luo S. , Bilimoria K. Y. , Crow J. , Cormier J. N. , Gonzalez-Angulo A. M. , Buzdar A. , Hortobagyi G. N. , Hunt K. 
Published: February 2017

92 Background: American Joint Committee on Cancer (AJCC) staging of breast cancer is used to determine prognosis, yet survival of patients within each stage shows wide variation and remains unpredictable. We hypothesized that differences in underlying biology might influence some of this variation and that the addition of biologic markers to current AJCC staging parameters would improve predictions of prognosis. Methods: We identified an initial cohort of 3,728 patients at our center who underwent surgery as the first intervention between 1997 and 2006. We used a Cox proportional hazards model, with backward stepwise exclusion of factors and stratified on pathologic stage (PS), to test the added significance of modified Black’s nuclear grade (G), the presence of lymphovascular invasion (L), estrogen receptor status (E), progesterone receptor status (P), or combined ER and PR status (EP), or combined receptor subtype (ER+PR+HER2 [M]). We assigned values 0-2 to these disease-specific survival (DSS)–associated factors and then used different combinations to assess different staging systems. Surveillance Epidemiology and End Results (SEER) data was used as the external cohort (n=26,711) to validate the scoring system. Results: Median follow-up time for the initial cohort was 6.5 years, and the 5-year DSS rate was 97.4%. Six different staging systems were used to predict 5-year patient outcomes: PS, PS+G, PS+GL, PS+EG, PS+GEP, and PS+GM. We compared 5-year DSS rates, Akaike’s information criterion (AIC) and Harrell’s concordance index (C-index) for each staging system. We found that the PS+GEP staging system was most precise with lowest AIC (1927.3) and had the highest C-index (0.80). The ability of the PS+GEP system to stratify outcomes was confirmed in the internal bootstrapping samples and the external validation cohort. Conclusions: Our results validate a new staging system that incorporates tumor grade, ER and PR status into current AJCC staging for breast cancer. We recommend that biologic markers be incorporated into revised versions of the AJCC staging system for patients undergoing surgery as their first intervention.
Treatment of ductal carcinoma in situ (DCIS) with lumpectomy and accelerated whole breast radiation therapy with concomitant boost (ARTB).
Authors: Chadha M. , Portenoy J. , Boolbol S. K. , Kierstin L. , Baoch-Abaje K. , Harrison L. B. 
Published: February 2017

93 Background: The efficacy of accelerated radiation therapy (RT) for treating early stage invasive breast cancer has been established (Whelan T et al: NEJM, February 2010). But the role of accelerated schedules in treating patients with DCIS still needs to be defined. We have previously described the feasibility and low toxicity when using ARTB after lumpectomy (Chadha M et al: Int J Radiat Oncol Biol Phys 2007; 69). The objective of this study is to evaluate early outcomes in patients with DCIS treated with lumpectomy and ARTB, and to compare local recurrence rates of ARTB and conventional fraction (fr) RT with sequential boost (CRT). Methods: This study includes patients diagnosed to have primary DCIS treated with lumpectomy and RT. Patients with DCIS who had history of contralateral synchronous or metachronous invasive cancer were excluded. We identified 215 patients from our breast cancer database as having met this selection criteria; 54 patients received ARTB on an IRB approved protocol, and 161 patients matched by prognostic factors constituted the comparative CRT group. ARTB delivered 40.5Gy in 15fr to the breast, and with concomitant boost 45Gy in15fr was delivered to the lumpectomy boost volume. CRT delivered 46.8Gy in 26fr with sequential boost of 14Gy in 7fr. The patients were well matched with no significant difference in the distribution of known prognostic factors including age, nuclear grade, margin status, receptor status, and Body Mass Index between the groups. Results: The overall median follow up was 3.5 years (0.5 years–11.4 years). Actuarial 5-year local relapse-free survival was 95%. The actuarial 3-year local relapse rate was 2% and 0% for CRT and ARTB groups, respectively (p = 0.22). Local recurrence was observed in 9 patients with a median time to failure of 4.3 years (0.5 years to 8.6 years); 4/9 had grade 3 DCIS; 1 patient with grade 3 had close final margin (<1 mm); 5/9 patients received hormone therapy. Conclusions: With the follow up to date, we observed excellent outcomes in patients with DCIS treated by lumpectomy and RT. These preliminary results suggest comparable local control between ARTB and CRT. Additional studies and longer follow-up are needed.
Cosmetic outcome 1, 2, 3, and 4 years after intraoperative radiotherapy or external beam radiotherapy for early breast cancer: An objective assessment of patients from a randomized controlled trial.
Authors: Keshtgar M. R. , Williams N. R. , Corica T. , Saunders C. , Bulsara M. , Joseph D. J. ,   on behalf of the TARGIT Trialists' Group
Published: February 2017

94 Background: The randomized controlled TARGIT Trial was designed to determine noninferiority between the novel technique of TARGIT [intra-operative radiotherapy with Intrabeam (Carl Zeiss, Germany)] and conventional external beam radiotherapy (EBRT) in women with early breast cancer. The main outcome objective is risk of local relapse within the treated breast. We report here data from a subprotocol assessing cosmesis in 114 women over 50 years old participating in the TARGIT Trial from one center (Perth, Australia). Methods: Frontal view digital photographs from were assessed, blind to treatment, using specialist software (BCCT.core 2.0, INESC Porto, Portugal) that produces an objective composite score based on symmetry, color, and scar. Data on patient and tumor characteristics were obtained from hospital notes. Statistical analysis was by generalized estimating equations (GEE) on all data, and logistic regression analysis at year 1 only. Results: Photographs were taken at baseline (before surgery) and 1, 2, 3, and 4 years after initial breast-conserving surgery; none of the 114 patients had subsequent breast surgery. Median age at randomization was 62 years (IQR 56 to 68). The composite scores were dichotomized into Excellent and Good (EG), and Fair and Poor (FP). There was a nonsignificant 45% increase in the odds of having an outcome of EG for patients in the TARGIT group relative to the EBRT group (OR=1.45, 95%CI 0.78 – 2.69, p=0.245) after adjusting for tumour size. The results were similar when adjusted for tumor grade and age of the patient. For year 1 there was a statistically significant 2.35 fold increase in the odds of having an outcome of EG for patients in the TARGIT group relative to the EBRT group (OR=2.35, 95%CI 1.02 – 5.45, p=0.047) after adjusting for age of the patient, tumor size, and grade. Conclusions: These results confirm a significantly better cosmetic outcome with TARGIT compared to EBRT in the first year after surgery.
The impact of breast reconstruction on the decision to undergo contralateral prophylactic mastectomy.
Authors: McGhan L. J. , Pockaj B. A. , Gray R. J. , Bagaria S. P. , McLaughlin S. A. , Casey W. J. , Rebecca A. M. , Wasif N. 
Published: February 2017

96 Background: In the last decade there has been an increase in the incidence of contralateral prophylactic mastectomy (CPM) for unilateral breast cancer. Although many factors have been proposed to explain this trend, the impact of breast reconstruction on the decision to undergo CPM has not been extensively studied. Methods: A retrospective review of breast cancer patients from Surveillance, Epidemiology and End Results (SEER) registry data (2004-2008) was conducted. Characteristics of patients undergoing CPM were evaluated. Results: 71,176 patients with a diagnosis of stage I-III infiltrating ductal or lobular breast cancer underwent mastectomy for their primary lesion. Among these, 10,558 patients (15%) underwent a CPM. A significantly higher proportion of women undergoing CPM had reconstruction performed (44%) than those patients not undergoing CPM (13%), p<0.001. On multivariate analysis (Table), significant variables predicting CPM included age <50 years (OR 10.12), breast reconstruction (OR 3.58), and lobular histology (OR 1.41), all p<0.001. Of the 12,466 patients (18%) who underwent reconstruction, 4,636 (37%) had implant reconstruction, 4,498 (36%) had tissue reconstruction, and 1,122 (9%) had combined tissue/implant reconstruction (no data for 18%). On multivariate analysis, predictors of reconstruction included age <50 years (OR 20.5; CI 18.5-22.7), year of surgery (2008 vs. 2004; OR 1.60; CI 1.49-1.71), low tumor grade (OR 1.19; CI 1.13-1.25) and ER+ status (OR 1.16; 95% CI 1.10-1.23). The use of radiation therapy was associated with a lower likelihood of pursuing reconstruction (OR 0.61; CI 0.58-0.65). Conclusions: Apart from age, the factor most strongly associated with CPM is the decision to have reconstructive surgery performed. This suggests that CPM may not be purely associated with risk-reduction but also with treatment factors such as cosmesis. [Table: see text]
The use of trastuzumab in Japanese patients with HER2-positive advanced or metastatic gastric cancer.
Authors: Sawaki A. , Ohashi Y. , Omuro Y. , Satoh T. , Hamamoto Y. , Boku N. , Miyata Y. , Takiuchi H. , Ohtsu A. ,   the ToGA Trial Japanese Investigators
Published: February 2017

102 Background: The Trastuzumab for Gastric Cancer (ToGA) study showed the efficacy of trastuzumab for HER2-positive gastric cancer (HGA). The aim of this study is to evaluate the benefit of trastuzumab for Japanese HGA patients. Methods: ToGA was an open-label, international, phase III, randomized controlled trial undertaken in 122 centers in 24 countries. Median overall survival (OS) was 13.8 months in those assigned to trastuzumab plus chemotherapy (C+T) compared with 11.1 months in those assigned to chemotherapy alone (C) with hazard (HR) ratio of 0.74. Subgroup analyses of patients enrolled from Japan were undertaken to estimate the hazard ratio (HR) for OS in the Japanese population. Based upon the prescribed protocol for Japan, we calculated HR using multiple Cox regression model with prespecified covariates in the ToGA study in order to make up for the small number of Japanese patients and reduce the bias in the baseline characteristics between two groups. Results: Sixteen institutes participated and 102 patients were enrolled, of which 101 patients were evaluable for this research. The median OS was 15.9 months in C+T arm versus 17.7 months in C arm. The HR for OS was 1.00 [95% CI: 0.59-1.69]. However, the HR for OS adjusted for the above covariates was estimated to be 0.68 [95% CI: 0.36-1.27]. There were differences between C+T arm and C arm in some baseline characteristics. Higher frequencies were seen in C arm as follow: intestinal type, prior gastrectomy, and smaller number of metastatic sites. For HER2 status, the percentage of patients with IHC0/FISH+ was lower in C+T arm (5.9%) than in C arm (18.0%), while that of patients with HER2 status IHC2+/FISH+ was higher in C+T arm (35.3%) than in C arm (26.0%). Conclusions: Although ToGA's overall OS HR = 0.74 (p = 0.0046), in the Japan patient subgroup, the unadjusted hazard ratio was 1.00. However, there was an imbalance of the baseline characteristics between the treatment arms in Japanese population. When adjusted for these characteristics, the HR was 0.68 which is similar to those in the ToGA study. Adding trastuzumab to chemotherapy in Japanese population appears to confer a similar magnitude of benefit compared to the whole population enrolled in the ToGA study. [Table: see text]
Progression-free survival and time to progression as surrogate markers of overall survival in patients with advanced gastric cancer: Literature-based analysis of 36 randomized trials.
Authors: Shitara K. , Ikeda J. , Mizota A. , Kondo C. , Nomura M. , Yokota T. , Takahari D. , Ura T. , Muro K. , Matsuo K. 
Published: February 2017

103 Background: We evaluated the potential of progression-free survival (PFS) and time to progression (TTP) to act as surrogates of overall survival (OS) in clinical trial settings by a comprehensive literature-based analysis. Methods: Randomized trials of systemic chemotherapy for advanced gastric cancer were identified by comprehensive electronic and manual search. Correlations between PFS/TTP and OS were evaluated. Results: Thirty-six trials with a total of 83 treatment arms and 10,484 patients were selected for analysis. The nonparametric Spearman rank correlation coefficient (p) between median PFS/TTP and OS was 0.70 (95% CI, 0.59 to 0.82) and the correlation coefficient between hazard ratios in PFS/TTP and OS was 0.80 (95% CI, 0.68 to 0.92). Correlation tended to be higher in non-Asian (p = 0.80; 0.61-0.98) than Asian trials (p = 0.67; 0.39-0.94), higher in trials reporting PFS (p = 0.85; 0.72-0.97) than in those reporting TTP (p = 0.60; 0.24-0.97), and higher in trials in patients with measurable lesions only (p = 0.91; 0.77-1.00) than in those including non-measurable lesions (p = 0.71; 0.50-0.93), albeit that none of these differences was significant. Conclusions: Our results indicate that improvements in PFS/TTP in advanced gastric cancer strongly correlate with improvements in OS. PFS/TTP may be an appropriate surrogate for OS in clinical trials for advanced gastric cancer. No significant financial relationships to disclose.
Phase I study of cediranib in combination with cisplatin plus fluoropyrimidine (S-1 or capecitabine) in Japanese patients (pts) with untreated advanced gastric cancer (AGC).
Authors: Nakajima T. E. , Satoh T. , Muro K. , Yamada Y. , Shimada Y. , Takahari D. , Hayashi H. , Taku K. , Shi X. , Boku N. 
Published: February 2017

111 Background: Cediranib (AZD2171) is an oral, highly potent inhibitor of VEGF signalling with activity versus all three VEGFRs and c-Kit. Combination therapy with cisplatin + oral fluoropyrimidine is commonly used as first-line treatment for AGC. This phase I study assessed cediranib in combination with cisplatin/S-1 or cisplatin/capecitabine in Japanese pts with previously untreated AGC. Methods: Eligible pts received cediranib 20 mg/day and either cisplatin 60 mg/m2 iv, day 1 + S-1 40–60 mg bd, days 1–21, q5w (Arm A) or cisplatin 80 mg/m2 iv, day 1 + capecitabine 1000 mg/m2 bd, days 1–14, q3w (Arm B). The primary endpoint was safety and tolerability. Secondary endpoints included assessment of steady-state pharmacokinetics (PK) of cediranib and chemotherapy alone and in combination. Preliminary efficacy was an exploratory objective. Adverse events (AEs) were evaluated according to CTCAE v3.0. Results: Between Aug–Dec 2009, 14 pts (median age, 60.5 [27–72] years; male, n = 9; PS 0/1, n = 7/7) were recruited to Arm A (n = 6) or Arm B (n = 8). The safety profile in both arms was consistent with that of the individual agents. There were no unexpected toxicities. All pts experienced ≥1 AE. Dose-limiting toxicities were reported in 1 pt in Arm A (decreased appetite) and 1 pt in Arm B (decreased appetite, fatigue, hyponatremia). The most common AEs in Arm A were decreased appetite, fatigue, nausea, diarrhoea, decreased weight and neutropenia (all n = 5; 83%), and decreased appetite, fatigue, nausea (all n = 8; 100%) and constipation (n = 7; 88%) in Arm B. Five (83%) pts in Arm A and 6 (75%) in Arm B experienced grade ≥ 3 AEs. Grade 3 AEs in > 1 pt were neutropenia (n = 3) in Arm A and hypokalaemia (n = 3), neutropenia, hyponatraemia and fatigue (all n = 2) in Arm B. Grade 4 syncope was reported in 1 pt in Arm A; this resolved on the same day it was observed. Preliminary efficacy and PK data will be presented. Conclusions: Cediranib 20 mg plus cisplatin/S-1 or cisplatin/capecitabine was generally well tolerated and considered suitable for further evaluation in pts with AGC. The safety profile of each regimen was comparable with the individual agents. No new toxicities were identified. [Table: see text]
Adjuvant chemotherapy for gastric cancer: Less drug, same efficacy.
Authors: Liu T. , Li W. , Sun Y. , Shen K. 
Published: February 2017

114 Background: Adjuvant chemotherapy is proved to improve survival in gastric cancer by meta-analyses. However, no evidence showed the best regimen. We conducted a retrospective analysis to compare triplets with doublets in the adjuvant setting. Methods: We collected data from January 2004 to December 2008 from patients performed radical surgery and adjuvant chemotherapy. Doublets were defined as 5-FU 750 mg/m2 (d1- 5) or capecitabine 1,000 mg/m2 (d1-14) plus cisplatin 60 mg/m2 (d1) or oxaliplatin 130 mg/m2 (d1), while triplets had epirubicin 50 mg/m2 (d1) added. Chemotherapy was initiated within 6 weeks after surgery, repeated every three weeks and planned for 6 cycles. Patients were followed up in the outpatient clinic until death or April 30, 2010. Cox proportional-hazard model and chi-square test were used to test statistical difference. Results: A total of 316 patients (210 in doublets, 106 in triplets) had a median follow-up time of 47 months. 77 patients died at the end of follow-up (3-year survival of 67.4%).Two groups were well balanced except age (median age of 57 in doublets, 51 in triplets, p < 0.001). All the patients tolerated well, with few grade 3/4 side effects (21.9% in doublets, 30.2% in triplets, p = 0.107). Two groups had similar disease-free survival (median DFS, 16 months vs. 23 months, p = 0.656) and overall survival (3-year survival rate, 59.6% vs. 64.8%, p = 0.293). Subgroup analysis showed the same benefit on survival between the two groups. Conclusions: Our study suggested doublets and triplets had the same efficacy as the adjuvant chemotherapy. Furthermore, doublets seem more cost-effective. [Table: see text] No significant financial relationships to disclose.
Comparison of the 6th and 7th editions of the UICC TNM staging system for gastric cancer: Results of a Chinese single-institution study of 1,503 patients.
Authors: Wang W. 
Published: February 2017

117 Background: To evaluate the prognostic efficacy of the 7th edition TNM classification compared to the 6th edition in gastric cancer patients. Methods: A total of 1,503 gastric cancer patients undergoing surgical resection were staged using the 6th and 7th edition staging systems. Homogeneity, discriminatory ability, and monotonicity of gradients of the two systems were compared using linear trend X2, likelihood ratio X2 statistics, and Akaike information criterion (AIC) calculations. Results: Significant differences in five-year survival rates were observed for the “T,” “N,” and “M” subgroups using the 7th edition system, except for stage N2 and N3 patients in the 6th edition system. There were no significant differences in survival between IB and IIA in the 7th edition system. Patients with stage IV disease due to T4/N3 in the 6th edition system who were downstaged to stage III in the 7th edition system had significantly better survival than those who remained at stage IV. The 7th edition system had higher linear trend and likelihood ratio X2 scores, and smaller AIC values compared with those for the 6th edition, which represented the optimum prognostic stratification. Conclusions: Our study suggested that the 7th edition system performs superior to the 6th edition in several aspects. No significant financial relationships to disclose.
Impact of c-kit mutations, including codons 557 and/or 558, on the recurrence-free survival after curative surgery in patients with GIST.
Authors: Watanabe T. , Cho H. , Yoshikawa T. , Tsuburaya A. , Kobayashi O. 
Published: February 2017

12 Background: Recently, c-kit exon 11 deletions, including codons 557 and/or 558, have been reported to predict a worse prognosis in GIST patients. However, it is difficult to prove the correlation between genotype and tumor aggressiveness in the imatinib- adjuvant era because exon 11 mutations respond well to imatinib. In this study, we evaluated the impact of c-kit mutational status on recurrence-free survival (RFS) after resection of primary GIST. Methods: Clinical and pathological characteristics of 89 GIST patients in our single institution study were retrospectively analyzed. Tumors were categorized into 4 subgroups based on their mutational locations; A1: mutated codons including neither 557 nor 558, A2: either 557 or 558, B1: only 557 and 558, B2: both 557 and 558. All of the patients underwent curative surgery, and none received adjuvant imatinib. The median duration of follow-up was 49 months. Results: Tumors originated from the stomach (n=75/89, 84%), small intestine (n=10), and colorectum (n=4). Mutation subgroup B was associated with both Fletcher and Miettinen high-risk categories. The 2-year recurrence free survival rate for A1, A2, B1, B2, was 84.9%, 85.7%, 50%, 57%, respectively. Group B2 had a significantly worse RFS than groups A1 (p=0.0004) and A2 (p=0.0014). Multivariate analysis for RFS indicated that only the mutational subgroup was a significant prognostic factor (p=0.03, HR=2.42). Conclusions: C-kit mutations, including both 557 and 558, affected the RFS of GIST patients after curative surgery, but those including either 557 or 558 did not. Our results indicate that the locations of c-kit mutations are associated with PFS, and they may therefore affect the selection of candidates with GIST for adjuvant imatinib. No significant financial relationships to disclose.
Nationwide trends in diagnosis and outcomes of gastrointestinal stromal tumors in the era of targeted therapy.
Authors: Witkowski E. R. , Smith J. K. , Ng S. , McDade T. P. , Shah S. A. , Al-Refaie W. B. , Tseng J. F. 
Published: February 2017

121 Background: Gastrointestinal stromal tumors (GISTs) have historically been inconsistently categorized in tumor registries. Discovery of c-kit expression in 1998 allowed for more precise diagnosis, and use of tyrosine kinase inhibitors for GIST in 2000 marked a new era in management. We examined nationwide trends in the diagnosis, management, and outcomes of GIST in this post-imatinib era. Methods: Patients ≥ 18 years old with GIST were identified in the SEER database 1998-2007, using the GIST-specific ICD-O-3 code. After a period of steady increase, incidence stabilized after 2001. Trends from 2002 to 2007 were examined. Univariate and multivariate analyses were performed. This cohort was further divided into 2002-2004 and 2005-2007 for survival analysis by Kaplan-Meier methods and Cox proportional-hazard ratios. Results: 3,604 patients were identified. There was a dramatic increase in diagnoses from 1998 to 2001 (109 to 376 cases, p < 0.0001), but no significant change from 2002 to 2007 (p = 0.572). During this period of stable incidence (2002-2007), the proportion of patients recommended for surgery continued to decrease (85.2% to 80.1%, p = 0.0006), while utilization of radiation (which dropped to 1.1% by 2001) remained relatively constant (p = 0.101). Anatomic distribution remained stable (p = 0.529), with stomach (52.9%) and small bowel (29.3%) predominating. There was also no change in stage distribution (p = 0.811). Late stage, black race, and advanced age were predictive of not receiving resection. Female sex, younger age, local disease, later year of diagnosis, and resection were associated with lower risk of death. Survival for patients diagnosed in 2005-2007 improved over 2002-2004 for both unresected (p = 0.027) and resected (p = 0.0998) groups. Resection was an independent predictor of survival in both periods (p < 0.0001). Conclusions: Incidence of GIST as identified in the SEER database has stabilized 2002-2007, likely reflecting more accurate diagnosis. Survival for both resected and unresected patients has improved since the introduction of imatinib, and continues upward. These population-level findings confirm the significant benefit of surgical therapy beyond clinical trials. No significant financial relationships to disclose.