tbuckley/cabot-search huggingface dataset:
Surgical margins and biochemical recurrence risk at 2 years for robotic prostatectomy: Comprehensive evaluation and CUSUM analysis of oncological outcomes.
Authors: Arjun Sivaraman, Rafael Sanchez-Salas, Dominic Prapotnich, Kaixin Yu, Fabien Olivier, Christian Doudeau, Stephane David, Eric Barret, Fernando P. Secin, Alexandre Ingels, Francois Rozet, Marc Galiano, Annick Mombet, Nathalia Cathala, Xavier Cathelineau
Journal: Journal of Clinical Oncology (2015)

80 Background: To evaluate the learning curve of Minimally Invasive Radical Prostatectomy (MIRP) in our institution and apply the cumulative summation (CUSUM) analytical technique to identify salient learning curve transition points in terms of oncological outcomes. Methods: Clinical, pathologic, and oncological outcome data were collected from our prospectively collected MIRP database to estimate Positive Surgical margin (PSM) and Biochemical Recurrence (BCR) trends during a 15 year period from 1998 to 2013. All the RPs (laparoscopic (LRP) / Robotic Assisted [RARP]) were performed by 9 surgeons. PSM was defined as presence of cancer cells at inked margins. BCR was defined as serum Prostate Specific Antigen (PSA) &gt;0.2 ng/ml and rising or start of secondary therapy. Surgical learning curve was assessed with the application of Kaplan-Meier curves, Cox regression model, CUSUM and logistic model in order to define the “transition point” of surgical improvement. Results: We identified 5,547 patients with localized prostate cancer treated with MIRP (3,846 - LRP and 1,701 – RARP). Patient characteristics of LRP and RARP were similar. The overall risk of PSM in LRP was 25%, 20% and 17% for the first 50, 50 to 350 and &gt;350 cases, respectively. For the same population, the 5-year BCR rate decreased from 21.5% to 16.7%. RARP started 3 years after the LRP program (after approximately 250 LRP). The PSM rate for RARP decreased from 21.8% to 20.4% and the corresponding 5-year BCR rate decreased from 17.6% to 7.9%. The CUSUM analysis showed significantly lower PSM and BCR at 2 years occurred at the transition point of 350 cases for LRP and 100 cases for RARP. In multivariable analysis, predictors of BCR were PSA, Gleason score, extra prostatic disease, seminal vesicle invasion and number of operations (p &lt; 0.05). Patients harboring PSM showed higher BCR risk (23% vs. 8%, p &lt; 0.05). Conclusions: Learning curve trends of MIRP in our large, single center experience showed significant reduction in PSM and BCR risk at 2 years are noted after the initial 350 cases and 100 cases of LRP and RARP, respectively.
GAIN-(C): Efficacy and safety analysis of imgatuzumab (GA201), a novel dual-acting monoclonal antibody (mAb) designed to enhance antibody-dependent cellular cytotoxicity (ADCC), in combination with FOLFIRI compared to cetuximab plus FOLFIRI in second-line KRAS exon 2 wild type (e2WT) or with FOLFIRI alone in mutated (e2MT) metastatic colorectal cancer (mCRC).
Authors: John A. Bridgewater, Andres Cervantes, Ben Markman, Salvatore Siena, Antonio Cubillo, Rocio Garcia Carbonero, Darren Sigal, Giuseppe Aprile, David Cunningham, Cristina Nadal, Carles Pericay, Leslie M. Samuel, Daniel Hochhauser, Jose Alejandro Perez-Fidalgo, Andrew Strickland, Cecile Guizani, Sophie Golding, Vanesa Lopez Valverde, Marion Gabriele Ott, Josep Tabernero
Journal: Journal of Clinical Oncology (2015)

669 Background: Imgatuzumab, a humanized engineered IgG1 anti-Epidermal Growth Factor Receptor (EGFR) mAb designed to enhance ADCC, showed promising clinical activity in a phase I trial including KRAS MT mCRC. This multicenter phase II study (NCT01326000) aimed to compare the combination of imgatuzumab with FOLFIRI to cetuximab plus FOLFIRI or FOLFIRI alone as second-line treatment in patients with both KRAS e2WT or e2MT mCRC. Methods: Patients underwent a mandatory fresh tumor biopsy at screening to assess KRAS exon 2 status. KRAS e2WT patients were randomized (1:1) to treatment groups 1 or 2 to receive imgatuzumab (1,400 mg IV on day 1 and 8 then q2-weekly) or cetuximab (400 mg/m 2 IV on day 1 followed by 250 mg/m 2 IV q-weekly) respectively plus FOLFIRI (standard IV chemotherapy). KRAS e2MT patients were randomized to groups 3 and 4 to receive imgatuzumab plus FOLFIRI or FOLFIRI alone respectively. Patients were stratified by EGFR expression, time to disease progression on first line treatment and prior treatment with bevacizumab. A run-in phase (n=6/group) was performed to confirm tolerability before recruitment proceeded. Results: 169 patients with an evaluable fresh tumor biopsy were randomized. Median PFS (Investigator reported) was 7.3 months in group 1 versus 6.1 in group 2 (HR, 1.13; 95% CI 0.69-1.86) and 5.2 months in group 3 versus 4.3 in group 4 (HR, 0.94; 95% CI 0.57-1.54). Adverse events of ≥ grade 3 included rash (42.5%, 9.8%, 31.8%, 0% in groups 1, 2, 3 and 4 respectively), hypomagnesemia (30.0%, 4.9%, 22.7%, 0% respectively) and neutropenia (20.0%, 29.3%, 25.0%, 21.4% respectively). Conclusions: The outcome was negative with respect to the primary efficacy endpoint (PFS) with no benefit seen for the addition of imgatuzumab to FOLFIRI in second-line in both KRAS e2WT and e2MT populations. We demonstrated that collection of fresh tumor biopsy is feasible in pretreated CRC. Clinical trial information: NCT01326000.
Combination Biologic Therapy as Initial Treatment for Follicular Lymphoma: Initial Results From CALGB 50701 - a Phase II Trial of Extended Induction Epratuzumab (anti-CD22) and Rituximab (anti-CD20)
Authors: Barbara Grant, John P. Leonard, Jeffrey L Johnson, Lale Kostakoglu, Eric Hsi, John C. Byrd, Jeffrey A. Jones, Sin-Ho Jung, Bruce D. Cheson
Journal: Blood (2010)
Prognostic indicators of aggressive disease in patients with locally advanced or metastatic prostate cancer: A focus on neutrophil to lymphocyte and platelet to lymphocyte ratios.
Authors: A. Dabaja, M. Menon, P. Agarwal
Journal: Journal of Clinical Oncology (2011)

62 Background: Prostate specific antigen (PSA) and Gleason Score (GS) are helpful in predicting aggressive disease. Recently, the neutrophil:lymphocyte ratio (NLR) and platlet:lymphocyte ratio (PLR) were identified as prognostic indicators in gastric cancer which has an inflammatory pathogenesis. We hypothesized that these indicators may be prognostic in prostate cancer which is also postulated to have an inflammatory mechanism of carcinogenesis. Our goal was to assess if NLR and PLR is predictive of aggressive prostate cancer, which will be measured by metastasis and overall survival in patients on hormonal therapy as treatment. Methods: We performed a retrospective analysis of 246 patients that were being treated with hormone therapy for either locally advanced or metastatic disease, or who were not surgical candidates or refused surgery. A logistic regression model was used to analyze various prognostic factors including total GS, pre-biopsy PSA, perineural invasion, % of core biopsies positive, NLR, and PLR. Endpoints studied were overall survival and metastasis. Results: The logistic regression showed only pre biopsy PSA as a predictor of metastasis (n=82). The increased risk when measured continuously was 0.6% increase in odds ratio (p&lt;0.015). When PSA was measured categorically the % biopsy cores positive were predictive of increased risk of metastatic disease with a 2.9% increase in odds ratio (p&lt;0.002). The % biopsy cores positive were predictive of a 3.7% increased odds ratio in cancer-specific mortality (p&lt;0.002). These results were controlled for age, which gave a 7% increase in odds ratio of overall survival (p&lt;0.049). Conclusions: Despite the thought that prostate cancer has an inflammatory pathogenesis, no correlation was found between N:L and P:L ratios and overall survival or bone metastasis in patients on hormone therapy for locally advanced disease. There was a negative correlation between increased % positive biopsy cores a decreased risk of survival. Further investigation is necessary to investigate the role of NLR and PLR as prognostic indicators in organ confined prostate cancer. No significant financial relationships to disclose.
Prognostic value of chronic inflammatory cell infiltrates in Duke's stage B and C colorectal cancer.
Authors: M. Christie, S. Prakash, R. N. Jorissen, A. Sakthianandeswaren, P. Gibbs, L. R. Lipton, J. Desai, J. Tie, D. J. Kerr, O. Sieber
Journal: Journal of Clinical Oncology (2010)

e14003 Background: Clinicopathologic staging provides limited predictive value for the prognosis of Dukes stage B and C colorectal cancer (CRC) patients, and there is an urgent need for new prognostic markers in this group. We have previously constructed a gene expression-based prognosis predictor which successfully classified both stage B and stage C patients into poor prognosis and good prognosis groups. This prognosis signature was enriched for down-regulated immune response genes, perhaps reflecting the anti-tumor effect of mononuclear chronic inflammatory cells (MCICs) comprising lymphocytes, plasma cells and macrophages, which commonly infiltrate CRCs. Here, we investigated whether scoring of MCICs in CRC provides useful prognostic information for stage B and C patients. Methods: H&E stained tissue sections from archival CRC specimens were retrieved for 155 stage B and 166 stage C patients enrolled in the VICTOR clinical trial. The average density of MCICs within tumour areas composed of > 60% neoplastic cells was scored independently by two anatomical pathologists. Areas of adenoma, ulceration, and necrosis were excluded from analysis. MCIC density was assessed at ×40 magnification and classified into low or moderate/high by each observer. Automated scoring of MCIC density using image analysis software was evaluated. Results: Scores of MCIC density were concordant between the two independent observers for 77% of cases (κ statistical, 0.53; 95% CI, 0.33-0.63). Excluding samples where scores were discordant, low density of MCICs was significantly associated with poor recurrence-free survival (hazard ratio, 2.00; 95% CI, 1.17-3.41; p = 0.011; Wald test) over a 6-year follow-up period when adjusted for patient age at diagnosis, tumor stage, adjuvant therapy, and rofecoxib treatment. Computer-based scoring of MCICs was achieved using image analysis software. Conclusions: The density of MCICs as assessed by light microscopy on H&E stained sections provides useful prognostic information for Dukes stage B and C CRCs, with a low density of MCICs associated with poorer recurrence-free survival. The application of image analysis software for scoring of MCICs in CRCs holds the potential for automation. No significant financial relationships to disclose.
Treatment outcome of enzalutamide against castration resistant prostate cancer in Japanese cohort.
Authors: Tatsuya Shimomura
Journal: Journal of Clinical Oncology (2016)

318 Background: Enzalutamide (ENZ) is next generation anti androgen agent and prolonged survival both of before chemotherapy and after chemotherapy setting. In japan, it was approved to use against castration resistant prostate cancer (CRPC) from June 2014 and there is few report of treatment outcome of this agent in Asian countries. Prostate cancer is well known with the racial difference and then we investigated the outcome of enzalutamide in Japanese cohort. Methods: Total of 120 CRPC cases were introduced enzalutamide from June 2014 to July 2015 in our department and were investigated (before chemotherapy in 57 cases (group 1) and after chemotherapy in 62 cases (group 2) (One case was unknown)). We compared treatment outcome of these two groups and compared with AFFIRM and PREVAIL. Results: Comparing group 1, group 2 was younger in age, higher PSA, lower hemoglobin, higher ALP, higher LDH and higher CRP at starting ENZ. In terms of survival, OS of group 1 was better than group 2 (12 month survival rate were 0.95 and 0.58, respectively. p = 0.0088). However there was no significant difference in PSA response between Group 1 and 2 (Mean PSA decline was 51.7% and 50.1%, respectively. p = 7764). PSA response rate (PSARR) ≥ a50% was 57.8 % (group 1) and 58.1% (group 2)( p = 0.985). And PSARR ≥ a50% did not affect survival in both groups. (p = 0.1152 and 0.1288, respectively). When comparing group 1 with PREVAIL trial, survival rate was similar but PSA response was poorer. And when comparing group 2 with AFFIRM trial, survival rate was worse but PSA response was similar. Conclusions: Although this study was retrospective and follow up period was not long, we concluded that docetaxel treatment before enzalutamide affected survival rate, however that did not affect PSA response. And there were differences in outcome between this Japanese study and major randomized clinical trials (PREVAIL and AFFIRM).
Emerging transcriptional landscape and putative therapeutic targets in young patients with metastatic colorectal cancer (CRC).
Authors: Christopher Hanyoung Lieu, Todd M. Pitts, Jihye Kim, Aik-Choon Tan, Wells A. Messersmith, Y. Nancy You, Cathy Eng, S. Gail Eckhardt
Journal: Journal of Clinical Oncology (2016)

605 Background: Patients younger than 50 yrs of age comprise roughly 10% of the total incidence of CRC, but the incidence in the younger population is increasing. Recent data suggest that younger patients are at higher risk of progression of disease and death from CRC. The purpose of this pilot study was to investigate genomic differences between younger and older CRC tumors to generate hypotheses regarding potential differences in tumor biology that may explain worse outcome in young patients. Methods: To determine genomic differences in tumors from younger and older patients with CRC, a cohort of metastatic microsatellite stable CRC tumors was selected using tumors from 9 younger patients (&lt; 35 yrs) and 7 older patients (&gt; 70 yrs). Total RNA was extracted from tumor tissues and sequenced with Illumina HiSeq 2000. On average, 45 million reads were obtained from individual tumor samples. Sequencing reads were mapped to the reference genome using Bowtie; exon junctions were mapped using TopHat and transcript assembly was performed using Cufflinks. Results: The median ages for the younger and older cohorts were 31 and 73, respectively. From the RNA-seq analysis, gene expression profiles from younger patients were enriched for pathways involved in cell proliferation. Specifically ERBB2, NOTCH3, CAV1 were upregulated in multiple pathways in young patients (p &lt; 0.00001). The expression pattern was noted to be different in older patients with enrichment for CDX2, HMGB3, and EPHB2 within pathways involved in regulation of cell differentiation (p = 0.07). In total 77 genes were noted to be enriched in younger patients compared with older patients and 23 genes were enriched in older patients compared with young patients (FDR &lt; 0.05). These data, although preliminary, may provide support to explore ERBB2, NOTCH, and downstream signaling pathways as therapeutic targets for younger patients. Conclusions: In this pilot study, patients &lt; 35 yrs with metastatic CRC exhibited gene sets enriched for several cellular proliferation pathways, including significant upregulation of ERRB2, NOTCH3, and CAV1. These results are hypothesis generating and are being investigated further in a larger validation cohort.
Clinical specialist radiation therapists (CSRT): Creating capacity while improving quality of care.
Authors: Elizabeth Lockhart, Michelle Ang, Laura Zychla, Kate Bak, Lynne Nagata, Hasmik Beglaryan, Jillian Ross, Asad Husain, Carina Simniceanu, Eric Gutierrez, Padraig Richard Warde, Nicole Harnett
Journal: Journal of Clinical Oncology (2016)

124 Background: Ontario’s cancer system faces many challenges, including a rising incidence of cancer, aging population, increasingly complex cancer treatment, and health human resource (HHR) constraints. In response, Cancer Care Ontario and the Ontario Ministry of Health and Long Term Care collaborated on a project to assess whether a new advanced practice radiation therapist role – the ‘Clinical Specialist Radiation Therapist’ (CSRT) – could enhance access to high quality, innovative care by optimizing the use of HHR. Methods: This innovative model of care aims to enable radiation therapists with advanced training and accreditation (CSRTs) to assume responsibility for certain activities traditionally performed by radiation oncologists (ROs) while maintaining and improving the quality, accessibility and efficiency of radiotherapy (RT) for patients. To assess CSRTs’ impacts standardized metrics, including efficiency (access, wait times (WTs), team function) and quality (new/enhanced services, patient experience) measures, were used. Results: Currently there are 24 CSRTs in 9 of 14 regional cancer centres. 2014/15 data demonstrated that CSRTs can improve the efficiency of referral processes and clinic operations, decrease WTs, and increase capacity (2-28 additional patients seen in clinic/month). Optimized team function and time savings (5-66 RO hours/month) have been achieved through CSRTs’ assumption of certain patient assessment and treatment planning activities. Efficiencies have improved patient experience by facilitating quicker, more coordinated flow through the RT process, and greater continuity of care. Further, CSRTs have enhanced access to high quality RT, through &gt; 75 innovative initiatives (rapid access clinics, telemedicine consults). Conclusions: The CSRT role demonstrates how innovative models of care can improve patient access to high quality cancer care. With 24 CSRTs implemented, opportunities for analysis of factors which facilitate achievement of maximal impact and position sustainability exist. Such investigations could inform the refinement and further implementation of CSRTs in Ontario and other jurisdictions, improving patients’ access to RT more broadly.
Initial analytic validation of automated bone scan measures for treatment response assessment in patients with metastatic castration-resistant prostate cancer (CRPC).
Authors: G. H. Chu, M. S. Brown, H. J. Kim, M. Auerbach, C. Poon, B. Ramakrishna, A. Vidovic, D. W. Gjertson, M. J. Morris, S. M. Larson, J. G. Goldin, H. I. Scher
Journal: Journal of Clinical Oncology (2011)

e15174 Background: Evaluation of novel therapies for patients with CRPC has been limited by the lack of validated quantitative measures of bone tumor burden. Tools including visual assessment for determining progression based on lesion count and semi quantitative measures including the Bone Scan Index for predicting survival have been proposed. To date, a validated quantitative measure that can be used to assess either progression or response has not been available. We have developed a computer-aided (CAD) system for measurement of bone scan tumor burden including lesion count (LC), mean intensity (MI) and total area (TA). This study is to assess the range of normal variation and potential clinically meaningful cut points for changes in bone scan tumor burden. Methods: From an anonymized image data set, 20 CRPC patients were selected with a pair of bone scans acquired 6 to 24 weeks apart. All patients had failed at least 2nd line drug therapy; 10 were on no therapy, 10 received drug therapy between the two scans. Scans were acquired at 12 sites using a standard of care protocol including 20-25 mCi of Tc MDP, injected 2-4 hours before whole body scintigraphy. An automated CAD system was run for each patient on bone scans. Degenerative joint disease was removed manually by one of two board certified Nuclear Medicine Physicians. A two-sample Wilcoxon rank sum (Mann-Whitney) test was used to test for differences between the two groups in the ratio of LC (visit 2 / visit 1), change in MI and % change in tumor TA. Results: Table shows the median (IQR) for ratio of LC, change in MI and % change in TA. Differences between groups were significant for all measures. Conclusions: This preliminary data suggests total bone scan tumor area may be useful as an early surrogate outcome for CRPC patients with 30% change from baseline as a potential cut point to distinguish responders from non-responders. This work lays a foundation for validation of these measures against other clinically relevant outcome measures in a larger cohort. Ratio of LC Change in MI % change in TA No therapy 1.24 (0.56) -1.40 (14.80) 7.13 (27.61) Drug therapy 0.54 (0.68) -17.60 (16.30) -73.76 (45.38) P value 0.0012 0.0019 0.0003
Disparities and trends in prostate cancer staging over time
Authors: C. D. Mullins, V. D. Hsu, E. Onukwugha, I. H. Zuckerman, A. Hussain
Journal: Journal of Clinical Oncology (2008)

5160 Background: Appropriate staging is critical for the successful management of prostate cancer patients. Differences in tumor extent and the likelihood of being appropriately staged exist across racial/ethnic and age groups. This study examined patterns of prostate cancer staging from a nationally representative dataset. Methods: Prostate cancer staging data from the Surveillance, Epidemiology and End Results (SEER) Medicare files were categorized by SEER historic stage, defined as in-situ, localized/regional, distant or unstaged. Differences in staging across age and racial/ethnic categories and trends over time were examined to determine whether disparities persisted from earlier years, starting in 1997, to the most recently available data in 2002. Prostate cancer patients were stratified into 3 age categories (under 65; 65 to 79, and 80 or older) and 4 racial/ethnic groups: Non-Hispanic White [WNH], White Hispanic [HW], African American [AA], and Other. Results: Based on annual samples of 20,301 to 39,626 prostate cancer patients, the overall proportion who were unstaged decreased from more than 7% in 1997–1998 to less than 5% in 2001 and 2002. Significantly more patients were unstaged in the older age groups. Over time, a larger percentage of patients were staged across all racial/ethnic and age groups; however, the proportion of unstaged patients age 80 or older in the most recent year, 2002, remained high for WNH (13%), HW (20%) and AA (12%), compared to the groups under age 65 (2%) and ages 65–79 (3–4%). Of the staged patients, the proportion with localized/regional disease ranged from 94.2% to 95.5% across the six years, with a slight shift from distant to localized/regional staging. Conclusions: Disparities in tumor staging across racial/ethnic and age groups persist but these disparities have decreased somewhat over time. The highest proportion of unstaged patients occurred among AA ages 80+ in 1997 and among HW ages 80+ in 2002. Proportion of Unstaged Prostate Cancer Patients by Race/Ethnicity 1997 <65 65 - 79 80+ WNH 2.08% 5.19% 18.53% HW 4.30% 7.91% 18.18% AA 3.45% 7.39% 22.93% 2002 WNH 1.81% 3.20% 12.82% HW 1.92% 3.37% 20.38% AA 2.09% 3.68% 12.12% WNH=Non-White Hispanic; HW=White Hispanic; AA=African American Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis sanofi-aventis