tbuckley/cabot-search huggingface dataset:
The influence of treatment response on the impact of resection margin status after preoperative chemoradiotherapy in rectal cancer.
Authors: Eui Kyu Chie, Jooho Lee, Kyubo Kim, Seung-Yong Jeong, Kyu Joo Park, Jae-Gahb Park, Gyeong Hoon Kang, Sae-Won Han, Do-Youn Oh, Tae-You Kim, Yung-Jue Bang, Sung W. Ha
Journal: Journal of Clinical Oncology (2013)

505 Background: Circumferential resection margin (CRM) and distal resection margin (DRM) have different impact on clinical outcomes after preoperative chemoradiotherapy (CRT) followed by surgery. Effect and adequate length of resection margin as well as impact of treatment response after preoperative CRT was evaluated. Methods: Total of 403 patients with locally advanced rectal cancer underwent preoperative CRT followed by total mesorectal excision between January 2004 and December 2010. After applying the criterion of margin less than 0.5 cm for CRM and/or less than 1 cm for DRM, 158 cases were included as a study cohort. All patients underwent conventionally fractionated radiation with dose over 50 Gy and concurrent chemotherapy with 5-FU or capecitabine. Median follow-up duration was 44.9 months. Results: The 5-year overall survival (OS), disease-free survival (DFS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were 83.3%, 75.6%, 86.3%, and 77.4% respectively. CRM of 1.5 mm and DRM of 7 mm were cutting points showing maximal difference using maximal chi-square method. In univariate analysis, the shorter CRM was significantly related with worse clinical outcomes, whereas DRM was not. In multivariate analysis, CRM of 1.5mm, ypN, and perineural invasion were prognosticators for OS, DFS, LRFS, and DMFS. CRM was not a significant prognostic factor for good responders, defined as patients with near total regression or T down-staging. However, poor responders demonstrated a significant difference according to the CRM status. Conclusions: Close CRM, defined as 1.5 mm, was a significant prognosticator, but the impact was different for treatment response. Postoperative treatment strategy may be individualized based on this finding. However, findings from this study needs to be validated with larger independent cohort. [Table: see text]
Combined modality therapy (transurethral surgery, induction chemotherapy, followed by concurrent chemoradiotherapy) for bladder preservation for patients with muscle invasive bladder cancer: Preliminary report
Authors: C.-H. Hsu, C.-C. Lin, J. C. Chen, A.-L. Cheng, C.-Y. Huang, J. Chen, Y.-S. Pu
Journal: Journal of Clinical Oncology (2005)

4792 Background: Muscle-invasive urinary bladder urothelial carcinoma (UC) is traditionally treated with radical cystectomy. The combination of transurethral resection of the tumor (TURB), systemic chemo, & XRT may be as effective as radical cystectomy & thus allow the bladder to be preserved. We sought to incorporate our previously reported P-HDFL (Proc ASCO 20:344b, 2001; abstr 3128) or TP-HDFL (Proc ASCO 22:407b, 2003; abstr 1637) regimen into this multi-modality treatment approach. Methods: Between Sept 2002 & March 2004, we enrolled 20 patients (M:F = 15:5, median age 66, range 45 - 80) with muscle-invasive bladder cancer (stage T2–4NXM0, bladder:urethra = 18:2) in a trial of TURB, combination chemo & XRT (64.8 cGy using shrinkage-field technique) w/ concurrent chemo (CCRT). 11 patients underwent protocol A: Chemo w/ P-HDFL regimen (cisplatin 35 mg/m2, IV 24hr D 1, 8; 5FU 2,000 mg/m2 + leucovorin 300 mg/m2 IV 24hr D 1, 8, 15; q28d) for 3 cycles & concurrent PF regimen (cisplatin 25 mg/m2 IV 1hr; 5FU 425 mg/m2 IV 1hr weekly). 9 patients underwent protocol B: Chemo w/ TP-HDFL regimen (paclitaxel 70 mg/m2, IV 1hr D 1, 8; cisplatin 35 mg/m2 IV 24hr D 2, 9; 5-FU 2,000 mg/m2 + leucovorin 300 mg/m2 IV 24hr D 2, 9; q21d) for 3 cycles & concurrent TP regimen (paclitaxel 60 mg/m2 IV 1hr; cisplatin 25 mg/m2, IV 1hr weekly). Interval cystoscopy was employed after completion of combination chemo & when XRT achieved 40 cGy. Patients with < CR were referred for salvage cystectomy. Results: Up to April 2004, 14 patients had completed & 6 were still under the protocol treatment. All 6 patients who had CR after protocol treatment had functioning tumor-free bladder, 1 patient died of neutropenic sepsis during CCRT. Of the 7 patients did not have CR after protocol treatment, 5 underwent salvage cystectomy, & 2 who declined cystectomy subsequently died of distant mets 4 & 12 mo later. Conclusions: Sequential use of TURB, cisplatin/5FU-based combination chemotherapy, & cisplatin-based CCRT is feasible & may be considered a reasonable alternative in patients who are medically unfit for cystectomy or seeking an alternative to radical cystectomy. No significant financial relationships to disclose.
Effect of altering fibroblast integrin associated protein expression on the growth and protein expression of pancreas cancer cells.
Authors: Jill E. Shea, Kelly C. Hewitt, Courtney L. Scaife
Journal: Journal of Clinical Oncology (2013)

251 Background: The lack of success of current treatments for pancreatic ductal adenocarcinoma (PDA) may be due in part to the presence of the dense surrounding stromal response and the interactions between the stroma and cancer cells. We have shown that integrin associated proteins, in particular PINCH, are expressed to a higher degree in the stroma adjacent to the tumor cells and PINCH expression is positively correlated with poorer PDA patient outcomes. We hypothesize that decreasing PINCH protein expression in the tumor associated stroma will decrease the growth and expression of growth promoting proteins in PDA cells. Methods: Red fluorescent protein (RFP) stably expressing MiaPaCa-2 cells were co-cultured with WI38 fibroblasts, or WI38 fibroblasts with shRNA knockdown of PINCH protein (PINCH KD). Cell growth of the PDA cells alone and upon exposure to WI38 and PINCH KD fibroblasts was determined using RFP at 48 hours. PINCH, Akt, and pAKt protein expression in cultured PDA cells, exposed to media, WI38, or WI38 PINCH KD cells via a transwell system, were determined by western blot with values normalized to GAPDH protein expression at 48 hours. Results: MiaPaCa-2 cells grown in co-culture with WI38 cells had a 70%±5% increase in RFP, while those grown in co-culture with WI38 PINCH KD cells had a 40%±3% increase relative to MiaPaCa2 cells grown alone. In terms of relative PINCH protein expression there was an increase in MiaPaCa-2 (20%±5%) cells grown in co-culture with WI38 cells compared to alone but not when grown with PINCH KD (6%±3%). MiaPaCa-2 cells had a greater increase in AKT (47%±6% compared with 19%±4%) and pAKT (36%±5 and 22%±4%) in the cells grown with WI38 cells compared to PDA cells grown with WI38 PINCH KD. Conclusions: Reductions in fibroblast PINCH protein expression are associated with reductions in the growth of adjacent PDA cells, as well as the expression of growth enhancing proteins (PINCH, AKT, and pAKT). Since greater PINCH expression within PDA stromal cells is associated with poorer patient outcomes, understanding the mechanisms associated with this tumor-stromal interaction may provide intervention opportunities.
Survival outcome in resectable esophageal cancer: Single-center experience.
Authors: T. Tashi, Z. H. Torgersen, B. Willer, W. Gonsalves, I. Al-Howaidi, P. T. Silberstein, P. Townley, S. Subbiah, T. H. Lee, S. K. Mittal
Journal: Journal of Clinical Oncology (2010)

e14665 Background: We describe survival outcomes of patients undergoing resection for esophageal cancer at our institution. Methods: Patients undergoing esophagectomy are entered in a prospectively maintained database. After IRB approval the database was queried to identify patients who underwent esophagectomy for malignant disease from 2003-2009. Descriptive analysis was done for age, sex, histology and nodal status and preoperative treatment modality. Results: A total of 114 patients underwent esophagectomy for resectable malignancy from 2003-2009 by a single surgeon (SKM). The median age was 62 (34-84) with 96 (84.2%) males. Adenocarcinoma accounted for 96 (84.2%), squamous for 14 (12.3%) and high-grade dysplasia for 4 (3.5%) patients. Pretreatment clinical stage at diagnosis/postop pathological stages were as: stage 0 = 8 (7.0%)/17 (14.9%); I = 15 (13.2%)/26 (22.8%), IIA = 51 (44.7%)/23 (20.2%); IIB = 2 (1.8%)/21 (18.4%); III = 37 (32.5%)/24 (20.1%) and IV = 1 (0.9%)/3 (2.6%). Out of 114 patients, 71 (62.3%) patients received neoadjuvant therapy and of these 59 (51.8%) received chemoradiotherapy (CXRT) and 12 (10.5%) received only chemotherapy (CT) while 43 (37.7%) did not receive any preoperative treatment. Pathological down-staging was seen in 29 (49.2%) patients in CXRT group as compared to 4 (33%) in CT alone group (p = 0.31). Of these, complete pathological response (cPR) was seen in 13(22%) and 1(8.3%) (p = 0.28) respectively. 50 (43.8%) were node-positive while 64 (56.1%) where node negative and recurrence rate was 25 (50%) in node-positive group as compared to 14 (21.9%) in the node-negative group (p = 0.001). The overall recurrence rate was 39 (34.2%). In the neoadjuvant therapy group, median, 1- and 3-year survivals were 31.9 months, 75.4% and 40.6% respectively. The overall median, 1- and 3-year survivals were 40.8 months, 82.2% and 55.5% respectively. Conclusions: The survival outcomes from our data for patients undergoing neoadjuvant therapy followed by surgical resection compares favorably with published data. There was no statistical difference in cPR and down-staging of tumor between the CXRT group and CT alone group. Lymph node positivity is associated with higher recurrence rate when compared to node-negative patients. No significant financial relationships to disclose.
Hand–foot skin reaction, an anticipated dermatologic toxicity to pazopanib, with an unexpected low incidence: A systematic review of literature and meta-analysis.
Authors: Y. Balagula, S. Wu, X. Su, M. E. Lacouture
Journal: Journal of Clinical Oncology (2011)

365 Background: Pazopanib is a novel multikinase inhibitor that has been approved for the treatment of advanced renal cell carcinoma (RCC). It shares a similar spectrum of target receptors with sorafenib and sunitinib, including VEGFR, PDGFR, and c-kit tyrosine kinases. We have performed a systematic analysis to investigate the risk of HFSR to pazopanib. Exploring the differences in the incidence of HFSR between sorafenib, sunitinib, and pazopanib may offer additional insights into underlying mechanisms of this toxicity. Methods: Relevant studies were identified from PubMed (1998-2010) and abstracts presented at the American Society of Clinical Oncology Conferences between 2004 and 2010. Eligible studies were limited to prospective phase II-III clinical trials in which cancer patients were treated with pazopanib 800 mg orally once daily. Incidence, relative risk (RR), and 95% confidence intervals were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies. Results: A total of 942 patients from 10 prospective clinical trials were included in the analysis. The overall incidence of all-grade and high-grade HFSR was 4.5% (95% CI: 2.5-7.9%) and 1.5% (95% CI: 0.7-3.1 %), respectively. The relative risks of all-grade and high-grade HFSR to pazopanib monotherapy in comparison with controls were increased, reaching statistical significance for all-grade (RR=6.05, 95% CI: 1.11-33.12, p=0.038), but not for high-grade (RR=2.51, 95% CI: 0.12-51.9, p=0.55). The incidence of all-grade HFSR was significantly higher in patients with RCC as compared to patients with non-RCC malignancies (7.8% vs. 2.4%, p value=0.015). Conclusions: Despite sharing the same spectrum of target receptors with sorafenib and sunitinib, pazopanib is associated with an unexpectedly low risk of HFSR. Further investigations are needed to elucidate HFSR pathogenesis. [Table: see text]
PET-CT compared to no PET-CT in the management of potentially resectable colorectal cancer liver metastases: The costs implications of a randomized controlled trial.
Authors: Pablo Emilio Serrano Aybar, Amiram Gafni, Chu-Shu Gu, Jim A. Julian, Carol-anne Moulton, Steven Gallinger, Mark Norman Levine
Journal: Journal of Clinical Oncology (2016)

296 Background: PETCAM was a randomized trial evaluating the effect of PET-CT compared to conventional imaging (control) on the surgical management of patients with resectable colorectal cancer liver metastases (CRLM). It concluded that PET-CT did not result in frequent change in surgical management (8·0%, 21/263) with only 2·7% (7/263) avoidance of liver resections. In this study we conducted a cost analysis of these two arms up to one year following randomization. Methods: Health care utilization was collected for all study participants. Unit costs for hospitalization, physician services, chemotherapy and outpatient radiological and endoscopic procedures were obtained from administrative databases. Cost analysis was undertaken from the perspective of a third-party payer (i.e., Ministry of Health). Mean cost with its 95% credible interval was estimated using a Bayesian approach. Results: The estimated mean cost per patient in the PET-CT arm was CAN $45,454 (min-max: 1,340-181,420) and in the control arm, CAN $40,859 (min-max: 279-293,558), with a net difference of CAN $4,327, 95% credible interval -2,207 to 10,614. The primary cost driver was cost of hospitalization for liver surgery (+ $2,997 CAN for the PET-CT arm), mainly due to a longer length of hospital stay for the PET-CT arm compared to control (median 7 days vs. 6 days, P= 0·034) and a higher rate of postoperative complications (52/255, 20% vs. 13/128, 10%, P = 0·014). Baseline characteristics were similar between groups, including a similar number of liver segments involved with cancer, number of segments resected and type of liver resection performed. Conclusions: PET-CT does not appear to provide a significant clinical benefit in the surgical management of patients with resectable CRLM and it is not cost saving compared to control.
Analytic morphometrics: Assessing the role of sarcopenia and abdominal fat measurements in predicting survival for mRCC patients undergoing cytoreductive nephrectomy.
Authors: Nikhil Waingankar, Robert G. Uzzo, Elizabeth Handorf, Mohammed Haseebuddin, Anthony Corcoran, Zack Piotrowski, Marc C. Smaldone, Alexander Kutikov
Journal: Journal of Clinical Oncology (2016)

603 Background: Analytic morphomics have emerged as promising biomarkers of post-surgical outcomes. Decision-making in patients with mRCC is nuanced, as benefits of cytoreductive nephrectomy (CN) must be balanced against risks of delaying or forgoing systemic therapy. We sought to identify if pre-operative morphometrics predict survival in patients undergoing CN. Methods: We reviewed clinical, histopathologic, and radiographic data for patients who underwent CN at our institution from 2006-2012. Pre-operative cross-sectional images of T12 to L4 were assessed. Subcutaneous fat content (average distance from skin to fascia in midline); visceral fat (average distance from fascia to anterior vertebral body); and total body fat (visceral + subcutaneous fat) were quantitated. Psoas muscle area and density at L4 were indexed. Primary outcomes were OS and DSS. Results: 62 patients had complete data for review. Median age at surgery was 60 years (range 40-77), Charlson score was 1 (0-5), and ECOG PS was 0 (0-2). There were 42 patients with lung , 26 with bone, 8 with liver, and 5 with brain metastases (average metastatic sites per patient = 1.8). 46 patients (75.4%) received adjuvant systemic therapy. At 16 months follow-up, 23 patients (37.1%) died from disease, while 17 (27.4%) died of other causes. Median survival following surgery was 13 months (range 1-75). Morphomic metrics did not correlate with survival (Table). Conclusions: Pre-operative morphometrics did not correlate with survival outcomes in a cohort of patients undergoing cytoreductive nephrectomy. Perhaps acuity of mRCC onset and speed of progression reduce prognostic value of morphometrics in this population. [Table: see text]
Gastric epithelial dysplasia: Characteristics and long-term follow-up results after endoscopic resection according to morphological categorization.
Authors: Bong Eun Lee, Gwang Ha Kim, Dong Hoon Baek
Journal: Journal of Clinical Oncology (2015)

190 Background: Gastric epithelial dysplasia (GED) can be morphologically categorized into adenomatous and foveolar types. To date, there have been few studies on the clinical characteristics of GEDs according to the morphologic types. Therefore, we here aimed to elucidate the clinicopathologic characteristics of patients with GED and the long-term follow-up results after endoscopic resection according to the morphologic characteristics of GEDs. Methods: A total of 357 patients who underwent endoscopic resection for GEDs at Pusan National University Hospital between January 2008 and December 2009 were included in the study. Results: Patients with GED were divided into 3 groups: adenomatous (n = 167, 46.8%), foveolar (n = 103, 28.9%), and hybrid (n = 87, 24.3%) types. Compared to the adenomatous type, foveolar type lesions were more frequently located in the antrum/pylorus, flat/depressed lesions, and normal/reddish in color; and showed more frequent high-grade dysplasia. During the follow–up period (median, 37.3 months), the overall incidence of synchronous and metachronous lesions was 20.8% and 20.1%, respectively; of these, the incidence of synchronous and metachronous gastric cancer was 8.7% and 5.4%, respectively. There were no significant differences in the incidence of synchronous and metachronous lesions according to morphologic types. Conclusions: GEDs appear to have different clinicopathologic characteristics according to morphologic types. Irrespective of the morphology, synchronous and metachronous gastric cancers are commonly found after endoscopic resection of GEDs. Therefore, close follow-up surveillance after endoscopic resection of GEDs should be performed for all patients.
Racial differences in survival outcomes among men with localized prostate cancer.
Authors: Grace L. Lu-Yao, Dirk Moore, Yong Lin, Kitaw Demissie, Weichung Shih, Peter C. Albertsen, Robert S. DiPaola, Siu-Long Yao
Journal: Journal of Clinical Oncology (2013)

98 Background: This study addresses whether the recent favorable survival trends observed among contemporary prostate cancer patients can be extended to African American men who have historically suffered excess prostate cancer mortality. Methods: The study cohort consisted of men over age 65, who resided in the SEER catchment area and were diagnosed with T1-T2 prostate cancer (ICD-O-3 code C61.9) during the period 1992-2005. In order to quantify race-specific prostate cancer mortality, separate competing risk models were fit separately for Whites and Blacks. Results: This study includes 35,509 white men and 5,256 black men who received conservative management for localized prostate cancer. The median age of the patients is 76 years at diagnosis and the median follow-up is 106 months. Overall, African Americans have slightly higher adjusted prostate cancer mortality than Whites (hazard ratio [HR] =1.16; 95% confidence interval [C.I.] 1.03 – 1.29). The racial difference was more pronounced in men with moderately differentiated cancer (HR=1.24, 95% CI 1.05 – 1.45), compared to poorly differentiated cancer (HR=1.00, 95% C.I. 0.85 – 1.18). Further analyses by comorbidity status and income level revealed that African Americans and Whites have similar excellent prostate cancer survival if they lived in areas with incomes above the median. Conclusions: African Americans diagnosed in the contemporary PSA era have similarly excellent survival outcomes as their white counterparts if they lived in areas with incomes above the median. Further studies should be conducted to confirm these findings and assess care and health habits that may improve cancer control and outcomes among African Americans.
Prognostic implications of lymphangiogenic markers in early-stage NSCLC.
Authors: E. Sanmartin, S. Gallach, R. Sirera, C. Hernando, A. Honguero, R. Guijarro, M. Martorell, C. Camps, E. Jantus-Lewintre
Journal: Journal of Clinical Oncology (2011)

e21108 Background: The lymphatic system constitutes one of the most important pathways for tumor cell dissemination. The process of lymphangiogenesis is mainly regulated by VEGF family members. Specifically, the activation of VEGFR-3 by the binding of VEGF-C and VEGF-D is the initial signal stimulating the proliferation and migration of lymphatic endothelial cells. The aim of the present study was to analyze the expression of these genes in a cohort of resectable NSCLC patients and to correlate them with clinico-pathological variables and prognosis. Methods: RNA was obtained from tumor and normal lung specimens from 150 resectable NSCLC patients. RT-PCR was performed to assess the expression of VEGF-C, VEGF-D and VEGFR-3. Relative expression was normalized by an endogenous gene (GUS) using the Pfaffl formulae. Differences were considered statistically significant at p<0.05. Results: We found that tumor samples had a significant lower expression of VEGF-D compared to normal tissue (0.030X). In regard to the smoking status, the group of active smoking patients showed higher expressions levels of VEGF-C and VEGFR-3 genes (p=0.012 and p=0.014, respectively). There was s trend correlating lower expression of VEGF-D with lymph node metastasis. The survival analysis revealed that the group of patients with values of VEGF-D below the median had a significantly reduced OS rate (p=0.002). Conclusions: VEGF-D is a master control gene of the lymphangiogenic process and may have a crucial role in the development of metastasis, therefore the lower expression of this gene found in tumor samples compared with normal lung tissue needs to be further investigated. Moreover, the expression of VEGF-D below the median is a poor prognostic marker for OS in our cohort of early-stage NSCLC patients. Supported by grants PS09-01149 and RD06/0020/1024 from ISCIII.