tbuckley/cabot-search huggingface dataset:
Epigenetic inactivation of RUNX3 in preneoplastic lesions of colorectum
Authors: Manish Subramaniam, Jason Chan, Richie Soong, Kosei Ito, Yeoh Khay Guan, Reuben Wong, Thomas Guenther, Olivia Will, Chee Leong Chen, Marian Kumarasinghe, Yoshiaki Ito, Manuel Salto-Tellez
Journal: Clinical Cancer Research (2007)

B6  Background:  Based on widely prevalent epigenetic silencing of RUNX3 gene in invasive malignancies and precancerous gastric lesions, we hypothesized that RUNX3 inactivation by promoter methylation in colorectal polyps is an early molecular event in colorectal carcinogenesis.  Design and settings:  We examined RUNX3 protein expression by immunohistochemical analysis and promoter hypermethylation by methylation-specfic PCR (MSP) in 50 sporadic colorectal polyps, including 17 hyperplastic polyps (HPs), 14 serrated adenomas (SAs) and 19 sporadic traditional adenomas (sTAs), as well as 19 familial adenomatous polyposis (FAP) samples of 10 patients showing aberrant crypt foci (ACF) (n=91), small adenomas (SAds) (n=40) and large adenomas (LAds) (n=13).  Results:  Compared to normal colon (2/12, 16%) and sTAs (3/17, 18%), HPs (15/19, 79%) and SAs (8/14, 57%) displayed significant inactivation of RUNX3 (p
Graded prognostic assessment index for renal cell carcinoma with brain metastases.
Authors: Rohan Garje, Saurabh Dahiya, Vyshak Alva Venur, Lingling Du, Kwabena Osei-Boateng, Paul Elson, John H. Suh, Samuel T. Chao, Manmeet Singh Ahluwalia
Journal: Journal of Clinical Oncology (2013)

e15537 Background: The GPA is a commonly used prognostic index based on RTOG protocols in patients with brain metastases (BM). The purpose of this study was to evaluate the utility of GPA index in a contemporary cohort of renal cell carcinoma with brain metastases (RCCBM) at a larger tertiary care center to predict overall survival. Methods: IRB approval was obtained and the Cleveland Clinic Brain Tumor and Neuro-Oncology Center’s database was used to identify RCCBM patients (pts) treated in the recent era (2000-12). A proportional hazards model was used to assess OS, which was measured from the date of diagnosis of brain metastases to death or last follow-up. Results: 136 RCCBM (100 males), median age 60 years (range 32-79), were evaluated. Pts had a median of 2 (range 1-15) BM; Karnofsky Performance Scale (KPS) was 90-100 in 57%, 70-80 in 38% and &lt;70 in 5%. Extracranial metastasis was present in 93% of pts. OS was 15.0 months (95% C.I. 10.9-17.5). GPA for RCC consists of KPS (90-100, 70-80, &lt;70) and the number of BM present (1, 2-3, &gt;3).GPA was not prognostic for survival (p=.40), and neither GPA coding of KPS nor BM (1, 2-3, &gt;3) was associated with outcome (p=.90 and .26, respectively). In contrast, diagnosis of RCC to BM &gt;5 years, p=.004, brain as an initial site of metastasis, p=.005, normal hemoglobin, p=.01, a single BM, p=.02, controlled primary, p=.02, and age≤65 were found to be independently prognostic for improved OS. Using these factors, an alternative index can be formed. Conclusions: RCCBM specific GPA was notprognostic for OS in this study (p=.40), however a new index was developed based on a revised set of independent prognostic factors that was significant (p&lt;.0001). [Table: see text]
Defining predictors of early, intermediate, and late biochemical recurrence in men with clinically localized prostate cancer treated with minimally invasive radical prostatectomy.
Authors: Silvia Garcia Barreras, Igor Nunes-Silva, Rafael Sanchez-Salas, Fernando P. Secin, Victor Srougi, Mohammed Baghdadi, Eric Barret, Francois Rozet, Marc Galiano, Xavier Cathelineau
Journal: Journal of Clinical Oncology (2017)

113 Background: Follow up after radical prostatectomy should be tailored to clinical and pathologic characteristics. To determine predictive factors for early, intermediate and late biochemical recurrence (BCR) after minimally invasive radical prostatectomy (MIRP: lap and robot) in patients with localized prostate cancer (PCa). Methods: Prospective clinical, pathologic, and outcome data were collected for 6195 patients with cT1-3N0M0 PCa treated with MIRP at our institution from 2000 to 2016. None of them received neoadjuvant therapy. BCR was defined as PSA level greater than 0.2 ng/ml. Time to BCR was divided in terciles to identify variables associated with early ( &lt; 12 months), intermediate (12-36 months) and late BCR ( &gt; 36 months). Comparisons among groups were performed using ANOVA or Chi square test. Logistic regression models were built to determine risk factors associated with BCR at each time interval. Results: We identified 1148 (19%) patients with BCR. Median time to BCR was 24 months. Statistically significant differences were found between the groups concerning PSA preoperative, D’Amico risk, type of surgery, pT stage, pathological Gleason, positive margins and extracapsular extension. Multivariable logistic regression analysis showed preoperative PSA, positive nodes, positive surgical margins and laparoscopic surgery were associated with early BCR. Laparoscopic surgery was the only risk factor associated with intermediate term BCR. Significant predictors of late BCR included Gleason ≥ 7, ≥ pT3, positive surgical margins, lymph node dissection performance and laparoscopic surgery. Conclusions: Patients with high risk features like Gleason ≥ 7, ≥ pT3 and or positive surgical margins may develop late recurrence and deserve long term follow up. Identify patients with higher PSA and lymph node invasion has an important predictive role due to the risk of BCR within the first year. The association between laparoscopic technique and late BCR deserves further evaluation.
Charlson Score as prognostic factor in patients with castration-resistant prostate cancer.
Authors: Gustavo Jankilevich, Luciana Gennari, Matias Salazar, Claudio Graziano, Eduardo Saravia, Javier Belinky, Horacio Rey, Daniel Chirino
Journal: Journal of Clinical Oncology (2017)

242 Background: Tumor stage, Gleason score, PSA, Performance Status have been identified as important predictors of survival in prostate cancer. The Charlson Comorbidity Index (CCI) is a validated score used to stratify patients according to comorbidities. To evaluate the prognostic role of CCI in patients with CPRC. Methods: A retrospective study based on an analysis of medical records of 212 patients with CRPC treated at Durand Hospital between 2010-2015. The CCI was calculated for each patient and a correlation with overall survival was performed. Statistical analysis included univariate analysis and multivariate analysis (Cox regression). Patients were stratified according CCI ≤ 7.6 or ≥ 7.6. Survival analysis was performed using the Kaplan-Meier curve. Results: We analyzed records of 212 patients with prostate cancer, of which 59 were resistant to castration. Median age 69 years, the PFS with androgen blockade was 32.4 months. Patients with CPRC 54% perform chemotherapy as first-line treatment of castration resistance and 46% performed treatment of hormonal manipulation (Enzalutamide or Abiraterone Acetate). Median overall survival of patients with CCI &lt; 7.6 was 75 months versus 62 months for those with CCI &gt; 7.6 HR: 1.19 (1.03 to 1.36) p: 0.01. In multivariate analysis the ICC was an independent predictor of mortality in these patients HR: 1.23 (1.03 to 1.48) p: 0.02. (Table 1) CCI ≤ 7,6 was predictor to subsequent lines in CPRC setting. Gleason score, PS were independent predictors of survival. Conclusions: Based on our results we can consider the CCI as an independent predictor of survival in CPRC patients. CCI could be an useful tool useful to select patients in clinical trial and community settings. [Table: see text]
Overuse of sentinel lymph node biopsy with breast conserving surgery for clinical DCIS.
Authors: Natalie Beckman Jones, Rebecca A Ottesen, Joyce C. Niland, Tara M. Breslin, Jane C. Weeks, Melissa E Hughes, Doreen Marie Agnese, Stephen B. Edge
Journal: Journal of Clinical Oncology (2012)

1125 Background: The National Comprehensive Cancer Network (NCCN) guidelines recommend against sentinel lymph node biopsy (SLNB) for ductal carcinoma in-situ (DCIS) treated with breast conservation surgery (BCS). SLNB is appropriate with mastectomy because it precludes subsequent SLNB if invasive cancer is identified. However, SLNB is commonly performed with BCS for DCIS. We hypothesize SLNB use in the setting of BCS for DCIS varies and may be over used in some cancer centers. Methods: We examined 6,070 cases with initial biopsy showing DCIS presenting to 13 institutions participating in the NCCN Breast Outcomes Database from 1998-2009. Receipt of SLNB was defined as SLNB performed at any point in primary treatment for those with a final diagnosis of DCIS or at the first surgical procedure for those upstaged to invasive cancer. Characteristics of patients who did and did not have SLNB were compared using Chi-square tests. Logistic models adjusting for clinical and pathologic variables were performed to assess factors associated with use of SLNB. Results: Of 3,725 treated with BCS, 778 (20.9%) had SLNB. Among 2,345 treated with mastectomy, 1,484 (63.3%) had SLNB. Within BCS, patients presenting with clinical symptoms (vs. screening detected) were more likely to have SLNB (p=0.0006, OR: 1.76; 95% CI 1.31-2.36). For both groups, presence of comedo necrosis, year of diagnosis, and treating institution were predictors of SLNB (p&lt;0.0001). 1,171 (19.3%) were upstaged from DCIS at initial biopsy to invasive cancer on final pathology. 212 (18.1% invasive cancer group) had positive nodes. Use of SLNB increased over time from 1998-2009 in mastectomy group. Among BCS group, SNLB use decreased over the first half of the study period and then remained stable at approximately 15% across all centers. Conclusions: Although use of SNLB has decreased over time, a substantial percentage of patients undergoing BCS for DCIS receive SNLB. Practices vary considerably across centers. SLNB can be performed as a second procedure for those treated with BCS and identified with invasive cancer, thereby avoiding unnecessary risk of significant morbidity. Breast programs should review their practices to curtail the use of unnecessary surgery for women with DCIS.
Phase II trial of imatinib mesylate (I) in combination with docetaxel (D) in the treatment of patients (pts) with recurrent or persistent epithelial ovarian carcinoma (EOC)
Authors: L. Usha, M. L. Larson, N. Kazmi, T. O'Brien, L. A. Winkelman, J. Rotmensch
Journal: Journal of Clinical Oncology (2009)

e16552 Background: D has a known single-agent activity in advanced EOC with the response rate of at least 10%. I is a multi-targeted tyrosine kinase inhibitor shown in preclinical studies to decrease interstitial pressure in the tumor and facilitate influx of chemotherapeutic agents into the tumor. Methods: A single-institution trial was conducted in pts with advanced EOC in 2005–2007. The primary endpoint of the study was to determine a tumor response to the study combination. Pts were required to have received 1 or 2 prior chemotherapeutic regimens including a platinum compound and have performance status 0–2. Pts were to receive D 60 mg/m2 IV every 3 weeks and I 400 mg/day by mouth continuously. Planned target accrual for the first stage of the study was 15 pts with the preset minimum of 3 responses to proceed to the second stage. Tumor response was evaluated by RECIST criteria after every 3 cycles of D. Treatment was continued until disease progression or unacceptable toxicity. Results: Study was terminated early due to lack of response and significant toxicities. A total of 10 pts were enrolled. The age range of the pts was 55–79 with the mean age = 64. Five pts were evaluable for response and in all of them, cancer progression was observed after 3 cycles of combination therapy (0 responses). Five pts were taken off the study after 1 cycle of treatment either due to serious adverse events (SAEs) or disease progression. Among grade 3 and 4 SAE's observed in the study were 4 cases of hematological toxicity, 1 case of rash, 1 case of dizziness, and 1 case of deep venous thrombosis. The median progression-free survival for pts on the study was 7.5 weeks. Conclusions: Although the sample size of this study was small, the combination of I and D at the above doses appears ineffective in the population of moderately-pretreated women with advanced EOC. The majority of grade 3 and 4 SAE's were due to myelosuppression likely caused by D rather than I. No significant financial relationships to disclose.
Surgical center for ambulatory extended recovery: 30-day follow-up report of minimally invasive radical prostatectomy.
Authors: Arjun Sivaraman, Behfar Ehdaie, James Andrew Eastham, Jonathan Coleman, Karim A. Touijer, Matthew O'Shaughnessy, Daniel Stein, Robert Durany, Vincent Paul Laudone
Journal: Journal of Clinical Oncology (2017)

83 Background: In January 2016, we opened a novel, multidisciplinary ambulatory surgical center dedicated to perform complex cancer surgeries on an Ambulatory Extended Recovery (AXR) pathway specifically aimed at a 1-night or less hospital stay. This is a standalone facility separate from the inpatient hospital. The aim of this study is to evaluate the 30-day post-operative follow-up of Minimally Invasive Radical Prostatectomy (MIRP) performed in an ambulatory care setting. Methods: Between January 2016 – September 2016, we performed 424 MIRP in the AXR dedicated surgical center. The baseline demographics, cancer characteristics, surgical information and follow-up data were prospectively collected. We evaluated the 30-day complications, rate of falling-off the AXR pathway, rate of transfer to our inpatient hospital, number urgent care visits and need for re-admission. Results: MIRP was performed as robot assisted (85%) and laparoscopic (15%) procedures. The median (range) overall length of hospital stay was 27.1 (11.4 – 35.2) hours with a total operative time of 4.8 (3.1 – 9.3) hours with an estimated blood loss of 175 (20 - 800) ml. Nine patients (2.1%) fell off the AXR pathway and were transferred to the main hospital for further care. In the 30-day post-surgery period, complications were noted in 6.4% patients (Grade 1 -38%, 2 - 34% 3 – 27%), while urgent care visits and re-admission rates were 10.7% and 2.6% respectively. The median (range) time from surgery to re-admission was 16 (2 - 43) days. Conclusions: A multidisciplinary ambulatory surgical center with a dedicated AXR pathway represents a significant advancement in MIRP surgical care, providing a 1-night hospital stay in an ambulatory setting with acceptably low rates of complications, urgency care visits and re-admissions.
Can routine cavity shave margins (CSM) improve local control in breast cancer? Initial results of the SHAVE trial, a prospective randomized controlled trial of routine CSM vs. standard partial mastectomy (SPM).
Authors: Anees B. Chagpar, Brigid K. Killelea, Theodore N. Tsangaris, Meghan Butler, Karen Stavris, Xiaopan Yao, Fangyong Li, Veerle Bossuyt, Lajos Pusztai, Nina Ruth Horowitz
Journal: Journal of Clinical Oncology (2015)

1012 Background: Considerable controversy exists regarding the utility of routine CSM in patients undergoing partial mastectomy for breast cancer. We performed a prospective RCT to determine whether this practice results in a lower positive (+) margin rate. Methods: 251 patients with preoperative Stage 0-3 breast cancer undergoing partial mastectomy were randomized 1:1 to SPM or CSM (80% power to detect a reduction in (+) margin rate from 30% to 15%). Prior to intraoperative randomization, surgeons performed SPM per their usual practice. The sealed randomization envelope was then opened and surgeons were instructed either to take circumferential CSM or close. (+) margins were defined as tumor at ink for invasive cancer, and < 1 mm for DCIS. Results: The median patient age was 61 (range; 33-94). 61 (24.3%) had invasive cancer only, 50 (19.9%) had DCIS alone, and 129 (51.4%) had a combination of both. The median invasive tumor size was 1 cm (range; 0-6.5), and median DCIS size was 0.9 cm (range; 0-9.3). The groups were well-matched in terms of baseline characteristics (see table below). Margin status prior to randomization was not significantly different between the two groups (34.9% vs. 33.6%, p = 0.894). After randomization, those randomized to CSM had a significantly lower (+) margin rate than SPM (18.3% vs. 33.6%, p = 0.006). This was the primary endpoint of the study. Not all (+) margins were re-excised due to anatomic considerations; however, CSM resulted in a significantly lower re-excision rate than SPM (9.5% vs. 20.8%, p = 0.014). Conclusions: This is the first RCT to conclusively demonstrate that CSM halves the (+) margin and re-excision rate of SPM. Use of routine CSM may significantly reduce morbidity and cost of reoperation for margin clearance. Clinical trial information: NCT01452399. CSM (n = 126) SPM (n = 125) p-value Age (yrs); median 62 60 0.525 Invasive tumor size (cm); median (range) 1.0 (0 – 6.0) 1.0 (0 – 6.5) 0.639 Palpable (%) 20.6% 22.4% 0.761 Invasive lobular histology (%) 11.0% 7.8% 0.744 DCIS component (%) 69.0% 73.6% 0.486 DCIS size (cm); median (range) 0.9 (0 – 9.3) 1.0 (0 – 8.1) 0.775 Node positive 10.3% 10.4% 1.000 ER+ 90.6% 87.5% 0.527
Survival outcomes for patients with metastatic colorectal cancer (mCRC) based on primary site, right (R) colon versus left (L) colon versus rectal (Rec) primary: Results from the South Australian Registry of mCRC.
Authors: Yoko Tomita, Christos Stelios Karapetis, Carol Beeke, Rob Padbury, Guy Maddern, David Roder, Amanda Rose Townsend, Amitesh Chandra Roy, James Moore, Timothy Jay Price
Journal: Journal of Clinical Oncology (2014)

3540 Background: Previous reports have described differences in biology and outcome based on R or L sided primary bowel cancer. Possible differences in response to biological agents have also been reported. Methods: We explored the SA mCRC registry to assess differences in patient characteristics, treatment received, and outcomes based on if the primary was R colon (caecum to transverse colon), L colon (splenic flexure to sigmoid), or rectal. KM was used for survival outcomes and Cox proportional hazards regression modeling was used to assess defined prognostic markers. Results: 3,121 patients were analysed. 33.5% had R colon, 35.3% L colon and 26.7% rectal primary. Major differences between the groups are shown in the Table. There was no major difference between L and Rec. There were statistically significant differences between both R v L and R v Rec; R occurred more in females and older age, and had more poorly differentiated pathology. Biological agent use, chemotherapy (CT) use, and metastatectomy were all less common in R. KRAS MT rates were greater in R v L (p=0.007). Analysis of systemic therapy revealed similar rates of 1st line therapy, but different 2nd line; R 47% v L 60% v Rec 60% respectively. The mOS for the entire group R v L v Rec was 9.8 v 19.2 v 17.8 months. For the group who had active therapy defined as CT (+/- metastatectomy), mOS was R 15.5 v L 26.2 v Rec 26.3 months. For those (n=168) who underwent liver resection (+/- chemotherapy) 5 year survival was R 55%, L 58% Rec 55%. In patients treated with only CT, mOS was R 10.3 v L 15.1 v Rectal 15 months. Conclusions: There were no major differences noted between L colon and Rectal primary. Patients with R primary had more negative prognostic factors and indeed had inferior outcomes when compared to those with L or Rectal primary. Patients who were suitable for hepatic surgery had no difference in outcome. Right Left Rectum Female 51.2% 41.4% 34.9% Median age (years) 76 71.4 69.3 Synchronous 68.1% 64.6% 55.2% Poorly diff path 34.9% 21.8% 19.8% Liver/lung only 35.2%/4.2% 40.6%/7.4% 36.3%/12.8% KRAS exon 2 WT 52.2% 64.3% 60.4% Liver surgery +/- CT 6.8% 10.4% 4.7% CT +/- metastatectomy 51.4% 60.7% 64.6%
Autologous Stem Cell Transplantation with Thiotepa, Busulfan, and Cyclophosphamide Conditioning in Patients with Primary Central Nervous System Lymphoma: A Remarkable Outcome Form Single-Center Experience
Authors: Seyoung Seo, Jung Yong Hong, Dok Hyun Yoon, Jeong Hoon Kim, Young Hyun Cho, Chan-Sik Park, Jooryung Huh, Kyung Won Kim, Cheolwon Suh
Journal: Blood (2016)
Activation of P38MAP kinase in estrogen-positive invasive breast cancers: Relation with HER2 and downstream signaling phosphorylated proteins expression.
Authors: Jean-Louis Merlin, Alexandre Harle, Maeva Lion, Anne-Sophie Chrétien, Carole Ramacci, Agnès Leroux
Journal: Journal of Clinical Oncology (2013)

e11560 Background: P38 kinases are members of the mitogen-activated protein kinase (MAPK) family. In breast cancers MAPK, as well as PI3 kinase-AKT pathway signaling proteins have major implication in molecular oncogenesis and are extensively investigated as putative targets for therapy. The present study reports the investigation of the expression of P38MAPK and its phosphorylated form (p-P38MAPK) in clinical specimens of invasive breast carcinomas in relation with estrogen receptor and HER2 expression, as well as MAPK and PI3K signaling phosphorylated proteins. Methods: The expression of P38MAPK and p-P38MAPK as well as p-AKT, p-GSK3β, p-S6 kinase, p-MEK1, p-ERK1/2 were semi-quantitatively assessed using multiplex bead immuno-assay. The analyses were performed retrospectively in frozen specimens from 46 invasive breast tumors classified according to estrogen receptor (ER) and HER2 status. Results: All specimens were taken at diagnosis and validated for tumor content &gt;50%. Twenty-nine were ER+, 17 were HER2+, 10 were triple negative (TN) tumors. Analyses were performed in triplicate from total protein extracts and were achievable in all specimens. P38MAPK was found to be expressed in all tumor specimen and significantly (P=0.002) overexpressed in ER+ tumors. P38MAPK was lower in TN tumors than in all others. The median expression of phosphorylated-P38MAPK was also higher in ER+ than in ER- tumors and lower in TN tumors than in all others. HER2 status had no influence on P38MAPK and p-P38MAPK expression. No variation in the phosphorylation rate of P38MAPK was observed in relation with ER, HER2 or TN status. Significantly higher (P=0.0048) expression of p-AKT tumors was observed in HER2+ tumors. No significant difference in p-MEK1, p-GSK3β and p-S6K expression was evidenced in any other comparisons based on ER and HER2 expression subtypes. Conclusions: Investigation of the expression of multiple phosphorylated signaling proteins can be used as molecular biomarkers for personalized targeted therapy. In ER+ invasive breast cancer, the overexpression of P38MAPK could serve as biomarker for evaluation of P38MAPK inhibitors.