tbuckley/cabot-search huggingface dataset:
Survival analysis of breast cancer subtypes assessed by hormone receptors and HER2 tumor expression in Uruguayan women with operable breast cancer.
Authors: N. Camejo, V. Gonzalez, C. Castillo, L. Delgado, L. Ferrero, R. Fresco, G. K. Santander, S. Aguiar, S. Heinzen, A. Martinez, C. Meyer, G. Sena, G. Spera, L. Ubillos, F. Xavier, R. Rodriguez, G. Sabini
Journal: Journal of Clinical Oncology (2011)

e21064 Background: Breast cancer (BC) is an heterogeneous disease and the most common cause of cancer death in Uruguayan women. HER2 and hormone receptors (HR) tumor expression define BC subtypes with different prognosis and characteristics. We previously classified BC in the following subtypes: HR+/HER2-, triple negative (TN), HER2+ and reported their relation with clinical and pathologic features. The purpose of this study was to analyze the relationship between these biological subtypes and disease free survival (DFS) in Uruguayan BC patients (pts). Methods: We retrospectively reviewed clinical records from pts who underwent curative surgery for stage I-III invasive BC at the Oncology Units of 4 institutions in Montevideo, Uruguay, between March 2006 and March 2008. HR and HER2 status were assessed by immunohistochemistry (IHC). DFS was estimated using the Kaplan-Meier method and compared across groups using log rank statistics. Results: 169 pts were included ; median follow up was 43 months. At the time of the analysis 160 pts (94.7%) were alive and 141 (83.4%) free of relapse. One hundred and twenty three pts were HR+/HER 2 – (72,7%), 32 pts were TN (18.9%) and 14 pts were HER2 + (8.2%). Two-year DFS was 93.3%, 94% for HR+/HER2 -, 91% for TN and 71.4% for HER2+. HER2 + pts had a shorter DFS than HR+/HER 2- (p=0.03) and TN pts (p=0.11). The median survival was not reached for all the pts nor for any of the subgroups. Conclusions: In accordance with international reports our results indicate that HER 2+ pts have shorter DFS. The overlapping DFS curves and similar two-year DFS of HR+/HER2- and TN pts were not explained by the clinical and pathologic differences.
Prognosis of metastatic internal mammary sentinel nodes (IMSN) in breast cancer.
Authors: Eli Avisar, Shai Libson, Eduardo Perez
Journal: Journal of Clinical Oncology (2014)

103 Background: The presence of positive internal mammary nodes has historically been associated with a significant worse prognosis. Recent studies have also demonstrated a worse prognosis associated with drainage to the internal mammary nodes. Intense search for those nodes, biopsy, appropriate staging and modern treatment for positive IMSN might improve outcome. We sought to study the prognosis of pathologically positive IMSN at our institution. Methods: A retrospective analysis of a prospectively collected database including all breast cancer patients identified with an IMSN that was biopsied between 2005 and 2012 was performed. Demographics, histologic markers, patterns of recurrence as well as survival data were collected. Univariate and multivariate analysis were performed. Results: Thirteen of 82 patients with a biopsied IMSN were metastatic (16%). In 8 of those (62%), the biopsy resulted in a change in staging. In all cases of positive IMSN additional radiation to the internal mammary chain was added. Eighteen percent (18%) of positive nodes did not show drainage to the internal mammary basin during Lymphoscintigraphy. There was no statistical difference in regional and distant recurrences between the patients with positive IMSN and those with negative IMSN. Furthermore there was no difference in disease specific survival. Conclusions: Intense search for IMSN presence and biopsy of those nodes is associated with changes in staging and treatment for metastatic IMSN. In our study, pathologically positive IMSN were associated with a non- inferior prognosis than negative IMSN.
<i>Clostridium difficile</i> infection among children with cancer.
Authors: E. Tai, L. C. Richardson, J. Townsend, E. Howard, C. McDonald
Journal: Journal of Clinical Oncology (2010)

9577 Background: Children are increasingly being recognized as an emerging population at risk for Clostridium difficile infection (CDI). Children with cancer have an increased risk of developing CDI due to increased antibiotic exposure, immunosuppression and longer hospital stays. We examined CDI among children with cancer. Methods: We used 2000, 2003, and 2006 data from the Healthcare Cost and Utilization Project KIDS' Inpatient Database which provides national estimates of pediatric discharges from community, non-rehabilitation hospitals. We examined weighted discharges with either a primary or non-primary CDI diagnosis, calculated rates of CDI, and identified risk factors for CDI. Results: The rate of CDI was 15 times greater among children with cancer compared to children without cancer (17.7 vs. 1.1 cases/1,000 discharges). Children with cancer accounted for 21% of all pediatric CDI cases. We found six factors among children with cancer associated with a primary and non-primary CDI discharge diagnosis, respectively: age 1-4 vs age 15-18 years (OR=2.0,CI:1.3-3.0;OR=1.5,CI:1.3-1.7), admission in year 2006 vs 2000 (OR=1.7,CI:1.2-2.4;OR=1.7,CI:1.4-2.0), chemotherapy during hospital stay (OR=0.2,CI:0.1-0.2;OR=0.9,CI:0.8-1.0) and hospital stay of 3-5 days vs 0-1 day (OR=3.8,CI:2.1-7.2;OR=3.2,CI:2.3-4.5). Among children without neutropenia, leukemia vs solid tumor (OR=2.9,CI:1.9-4.6;OR=1.7,CI:1.4-1.9) and lymphoma vs solid tumor (OR=2.2,CI:1.1-4.3;OR=1.5,CI:1.2-1.9) were associated with a primary and non-primary CDI diagnosis, respectively. Conclusions: Children with cancer account for a large proportion of pediatric CDI cases. The risk of CDI is increasing among children with cancer. Prevention efforts to address CDI in this population should focus on younger children with leukemia and lymphoma. No significant financial relationships to disclose.
Natural language processing (NLP) of Internet conversations to evaluate prostate cancer (PC) patients’ perceptions of active surveillance (AS).
Authors: Mark Vikas Mishra, Michele Bennett, Armon Vincent, Olivia T. Lee, Costas D. Lallas, Edouard John Trabulsi, Leonard G. Gomella, Adam Dicker, Timothy Norman Showalter
Journal: Journal of Clinical Oncology (2012)

14 Background: Less than 10% of qualifying PC patients receive primary management with AS. Qualitative research aimed at identifying patient acceptance of AS has been identified as a national health research priority. The primary objective of this study was to determine if NLP of anonymous internet conversations (ICs) could be utilized to identify unmet public needs regarding AS. Methods: After obtaining IRB approval, English-language ICs regarding PC treatment with AS from 2002-2012 were identified using a novel internet search methodology. Web spiders were developed to identify, mine, and gather content from the internet for ICs centered on AS. All ICs identified were screened programmatically to remove any not-on-topic ICs. Collection of ICs was not restricted to any specific geographic region of origin. NLP was used to evaluate content and perform a sentiment analysis. Conversations were scored as positive, negative, or neutral. A sentiment index (SI) was subsequently calculated according to the following formula to compare temporal trends in public sentiment towards AS: [(#Positive IC/#Total IC) – (#Negative IC/#Total IC) x 100]. Results: A total of 464 ICs were identified. Sentiment increased from -13 to +2 over the study period. The increase sentiment has been driven by increased patient emphasis on quality-of-life factors and endorsement of AS by national medical organizations. Unmet needs identified in these ICs include: a gap between quantitative data regarding long-term outcomes with AS versus conventional treatments, desire for treatment information from an unbiased specialist, and absence of public role models managed with AS. Conclusions: This study demonstrates the potential utility of NLP to analyze ICs in order to provide insight into patient preferences and decision-making. Based on our findings, we recommend that multidisciplinary clinics consider including an unbiased specialist to present treatment options and that future decision tools for AS include quantitative data regarding outcomes after AS, so that patients can make decisions with an amount of information that is more similar to the resources available regarding radiation or surgery.
The impact of low-frequency KRAS mutations on the efficacy of anti-EGFR antibody for patients with metastatic colorectal cancer.
Authors: Tomomi Hikosaka, Kentaro Yamazaki, Satoshi Hamauchi, Takahiro Tsushima, Tomoya Yokota, Akiko Todaka, Nozomu Machida, Akira Fukutomi, Yusuke Onozawa, Hirofumi Yasui
Journal: Journal of Clinical Oncology (2014)

496 Background: The benefit of anti-EGFR antibody is limited to metastatic colorectal cancer with KRAS wild-type (WT). However, some KRAS WT patients have low-frequency KRAS mutation (low MT) by pyrosequencing. Recently, it is reported that the efficacy of anti-EGFR antibody on these patients was inferior to no KRAS mutation patients (no MT) (D. Tougeron et al, Ann Oncol. 2013). Methods: Patients were categorized as low MT or no MT according to pyrosequencing cut-off point, and we evaluated anticancer effect of anti-EGFR antibody in each group. Results: A total of 358 patients were analyzed KRAS genotype by pyrosequencing between April 2010 and February 2013 in Shizuoka Cancer Center. 217 (60.6%) patients were KRAS WT of the total, and 93 (42.9%) were low MT, while 124 (57.1%) were no MT among them. 51 of low MT and 53 of no MT patients were treated by anti-EGFR antibody therapy, and response rate (RR) were 41% (CR/PR/SD/PD 1/20/17/13) and 32% (CR/PR/SD/PD 0/17/21/15), median progression-free survival (PFS) were 164 days and 170 days, respectively. 15 of low MT and 11 of no MT patients received anti-EGFR antibody monotherapy, and RR were 33% (CR/PR/SD/PD 0/5/7/3) and 19% (CR/PR/SD/PD 0/1/4/9), PFS were 184 days and 91 days, respectively. 27 patients in both groups were refractory or intolerance to 5-FU/L-OHP/CPT-11, and RR were 37% (CR/PR/SD/PD 0/10/9/8) and 19% (CR/PR/SD/PD 0/5/13/9), PFS were 132 days and 140 days, respectively. In univariate and multivariate analysis, there was no difference of anticancer effect between low MT and no MT. Conclusions: Unlike the previous report, patients with low-frequency KRAS mutations also benefited from anti-EGFR antibody therapy. However, some other biomarkers such as NRAS, BRAF, PIK3CA might affect these results. Now we are evaluating the effect of these candidate biomarkers on these results, and we will report the update data in this meeting.
PECULIAR study: Phase II study of pemetrexed in combination with cisplatin in patients with advanced urothelial cancer.
Authors: Jae-Lyun Lee, Se-Hoon Lee, Yoon Ji Choi, Jin-Hee Ahn, Cheryn Song, Bum-Sik Hong, Jun Hyuk Hong, Choung-Soo Kim, Hanjong Ahn
Journal: Journal of Clinical Oncology (2014)

301 Background: Pemetrexed has demonstrated a favorable response with minimal toxicity when used as single agent as first-line and second-line treatment for advanced urothelial carcinoma. The safety and tolerability of pemetrexed plus cisplatin combination has been widely recognized in malignant mesothelioma. This trial was performed to evaluate the efficacy and safety of pemetrexed plus cisplatin in advanced urothelial carcinoma. Methods: Eligible criteria included chemotherapy-naïve advanced urothelial carcinoma, ECOG PS 0-2 and measurable disease. Pemetrexed 500mg/m 2 on day 1 with cisplatin 70 mg/m 2 on day 1 were administered every 3 weeks til disease progression or a maximal of 8 cycles. Primary endpoint was response rate (RR), and secondary endpoints were progression-free survival (PFS), overall survival (OS) and toxicities. Response was evaluated every 6 weeks according to the RECIST criteria v.1.0 and toxicities were assessed with NCI CTCAE v.3.0. Results: A total of 42 patients were enrolled and 2 patients were excluded because of different histology and concomitant malignancy. At the time of this analysis, 36 patients (median age 66 years, ECOG 0-1 100%, visceral metastasis 50.0%, recurrent disease 61.1%) were evaluable; 6 patients were too early to assess. Twenty four partial responses for an overall response rate of 66.7% [95% confidence interval (CI) 50.3-79.9%] were documented. Six patients had stable disease. The median PFS was estimated to be 6.9 months [95% CI 6.2-7.7 months]. The median OS was 16.3 months [95% CI 12.9-19.7 months]. The most common grade 3 or 4 toxicities were neutropenia in 33.3% of patients. No one experienced febrile neutropenia. Other grade 3 or 4 hematological and non-hematological toxicities were rarely observed (thrombocytopenia 6%, anemia 6%, transaminitis 6%, nausea 3%, anorexia 3%, edema 3%, dyspnea 3%). Conclusions: The combination of pemetrexed and cisplatin is very active, with an overall response rate of 66.7% and well tolerated in patients with advanced urothelial cancer. The final mature results will be presented in the meeting. Clinical trial information: NCT01490437.
Prognostic significance of Smac/DIABLO expression in renal cell carcinoma
Authors: Y. Mizutani, H. Nakanishi, K. Yamamoto, T. Nakamura, T. Nomoto, K. Mikami, K. Okihara, K. Yoneda, A. Kawauchi, T. Miki
Journal: Journal of Clinical Oncology (2005)

4657 Background: Smac/DIABLO was recently identified as a protein that is released from mitochondria in response to apoptotic stimulus and promotes apoptosis by antagonizing inhibitor of apoptosis proteins. In addition, Smac/DIABLO plays an important regulatory role in the sensitization of cancer cells to drug-induced apoptosis. However, little is known about the significance of Smac/DIABLO in various cancers including renal cell carcinoma (RCC). This study examined Smac/DIABLO expression in 78 normal kidneys and 78 RCCs, and investigated the prognostic significance. Methods: The level of Smac/DIABLO expression was quantified by Western blotting using non-fixed fresh frozen tissues. Results: Smac/DIABLO expression was lower in RCC, compared to the autologous normal kidney. 64/78 (82%) of RCC expressed Smac/DIABLO and 18% were negative, whereas 100% of normal kidney were positive. In Stage I/II RCC, 96% expressed Smac/DIABLO, whereas only 50% expressed Smac/DIABLO in Stage III/IV. Smac/DIABLO expression inversely correlated with the Grade of RCC. Patients with RCC expressing Smac/DIABLO had a longer postoperative disease-specific survival than those without Smac/DIABLO expression in the 5-year follow-up. Transfection with Smac/DIABLO cDNA enhanced cisplatin-mediated and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in RCC. Conclusions: The current study demonstrates for the first time that Smac/DIABLO expression was downregulated in RCC, and that no Smac/DIABLO expression in RCC predicted a worse prognosis. In addition, transfection with Smac/DIABLO sensitized RCC to cisplatin-induced and TRAIL-induced apoptosis. These findings suggest that Smac/DIABLO expression in RCC may be used as a prognostic parameter, and that enhancement of Smac/DIABLO expression in RCC may potentiate immunotherapy and chemotherapy. No significant financial relationships to disclose.
Phase II study of neoadjuvant sorafenib plus cisplatin and gemcitabine (S-CG) for patients with muscle-invasive transitional cell carcinoma of the bladder (MIBC): Results at the end of first stage (NCT01222676).
Authors: Andrea Necchi, Patrizia Giannatempo, Luigi Mariani, Emanuela Fina, Nicola Nicolai, Marzia Pennati, Nadia Zaffaroni, Elena Farè, Luigi Piva, Davide Biasoni, Mario Catanzaro, Tullio Torelli, Silvia Stagni, Massimo Maffezzini, Maurizio Colecchia, Biagio Paolini, Vera Cappelletti, Maria Grazia Daidone, Alessandro M. Gianni, Roberto Salvioni
Journal: Journal of Clinical Oncology (2014)

305 Background: The small, yet significant, survival advantage with neoadjuvant chemotherapy in MIBC needs to be improved. A rationale exists for inhibiting the RAF/MEK/ERK pathway and investigating S-CG combination in an ongoing open-label, single-group, phase II trial. Methods: Patients (pts) with T2-4N0 MIBC received 4 cycles of cisplatin 70 mg/m2 on day 1 and gemcitabine 1000 mg/m2 on day 1 and 8, every 3 weeks. Sorafenib 400 mg q12h was administered daily from day 1 to cystectomy. An optimal 2-stage Simon’s design is applied. 6 pathologic complete responses (pT0, primary endpoint) should be observed in the first stage before moving to full enrollment of 45 cases. Residual carcinoma in situ with no evidence of invasive tumor was considered as pT0. Intention-to-treat analysis was applied. Biomarker and circulating tumor cell (CTC) analysis is ongoing. Results: 23 pts were enrolled from 04/11 to 07/13. Thus far, 21 completed the treatment and are evaluable. Median age was 61yrs (IQR: 54-66). 11 had T2, 9 T3, and one a T4 disease. 6 pts had hydronephrosis at presentation. 19 pts underwent radical cystectomy. Eight pts (38.1%, 95% CI: 18.1-61.6%) had a pT0 and 2 pts a pT&lt;2. G3-4 side effects consisted of hematologic toxicity in 8 pts (38%), hand-foot syndrome (HFS) in 3 pts, hypertension and asthenia in 2 pts each. 9 pts (42.8%) needed a temporary interruption of sorafenib, 6 a dose reduction, and 2 suspended the drug. After a median follow up of 12.6 months, 3 pts (14.3%) had a recurrence or progression and died, the remaining are disease-free. Median increase from baseline to day 8 of second cycle was observed for VEGF levels (85.8 to 119.5 pg/mL). All pts had a stepwise reduction of CTC count/5mL blood by ScreenCell (median baseline of 8 [0-40] to 2[0-6]). 3 pT0 pts starting with cT3b disease had a decrease from baseline 21, 10, and 40 cells to ≤3 cells. Increase in circulating EpCAM±Muc-1 levels by CTC was seen in accordance with disease progression (PD). Conclusions: Sorafenib seems to enhance the efficacy of CG in this setting. If confirmed, research should delineate the mechanisms behind clinical benefit and characterize PD. Clinical trial information: NCT01222676.
Real-world treatment patterns in third-line patients with metastatic renal cell carcinoma (mRCC): The changing landscape in the United States.
Authors: Sumanta Kumar Pal, Elisabetta Malangone, Sharvari Bhurke, Magdaliz Gorritz, Lee Stern, John Coombs, James D. Turnbull, Xufang Wang, Zhimei Liu
Journal: Journal of Clinical Oncology (2013)

390 Background: Several targeted therapies (TTs) have become available in mRCC in recent years for first- and second-line use, including sorafenib (So), sunitinib (Su), bevacizumab (Be), temsirolimus (Te), everolimus (Ev), pazopanib (Pa), and most recently, axitinib (Ax). This study aimed to examine the current treatment patterns in mRCC patients who fail second-line therapy. Methods: Data were obtained from a large national U.S. claims database for patients with an RCC diagnosis and at least 3 lines of TT between January 1, 2004, and June 30, 2011. Patients were age 18 or older at diagnosis with at least 3 months of follow-up prior to initiation of third-line therapy. Patient characteristics and treatment patterns were examined for the final population. Results: A total of 812 mRCC patients initiated third-line therapy with So, Su, Be, Te, Ev, or Pa. The sample was majority male (70%) with a mean age of 60 years (SD=10.7). A large proportion of patients were from the South (42%), and the majority of the sample (72%) had commercial insurance. The most common sites of metastases at any time were lung (71%) and bone (52%). The most common first-line agent was Su (52%) and the most common second-line single agents were Te (25%) and Ev (17%). The most frequently used single-agents in third-line were Te (21%) and Ev (19%). Third-line treatment choice differed by year; Te (51%) was most common in 2007 while Ev and Pa were most common between 2009 and 2011. Additionally, the most frequently prescribed sequences of single agents were VEGF→mTOR→VEGF (25%), VEGF→mTOR→mTOR (25%), and VEGF→VEGF→mTOR (22%). Conclusions: The results demonstrate a rapidly changing therapeutic scenario for mRCC in the United States. The number of targeted therapies prescribed in third-line increased from 1 in 2006 to 4 in 2007 and 6 in 2011. This evolution of third-line therapies is possibly due to physicians adapting their practice with the advent of novel mRCC treatment options. These results are in line with the NCCN guidelines, with VEGF and mTOR being the most commonly prescribed first- and second-line single agents, respectively.
A new immunohistochemistry prognostic score (IPS) for recurrence and survival in pancreatic neuroendocrine tumors (PanNET).
Authors: Antonio Viudez, Filipe LF Carvalho, Zahra Maleki, Marianna Zahurak, Daniel A. Laheru, Alejandro Stark, Nilofer Saba Azad, Christopher Lee Wolfgang, Stephen Baylin, James Gordon Herman, Ana De Jesus-Acosta
Journal: Journal of Clinical Oncology (2016)

241 Background: We aimed to evaluate the expression and prognostic significance of N-myc downstream-regulated gen-1 (NDRG-1), O 6 -methylguanine DNA methyltransferase (MGMT) and Pleckstrin homology-like domain family A member 3 (PHLDA-3) by immunohistochemistry (IHC) and methylation analysis in resected pancreatic neuroendocrine tumors (PanNET). Methods: Ninety-two patients with resected primary PanNET and follow-up &gt; 24 months were included in this study. Nuclear staining for MGMT and PHLDA-3 were scored as 0, 1-5%, 6-50% and ≥ 51%; cytoplasmic NDRG-1 staining was scored based on intensity and pattern from 0 to 2. We then grouped IHC scores for MGMT (absent versus any expression); for NDRG-1 (0 versus 1 versus 2) and for PHLDA-3 ( &lt; 50% versus ≥ 51%). Finally, we developed an immunohistochemistry prognostic score (IPS) based on MGMT, NDRG-1 and PHLDA-3 IHC expression to predict disease free survival (DFS) and overall survival (OS). The discriminatory ability of multivariate models combining the IPS and important clinical variables was assessed with Harrel’s c-index (HCI) and a modification of Harrell’s c-index (mHCI). Results: DFS was significantly worse in patients without any expression of MGMT compared with those with any grade of expression (HR: 2.21; 95%CI: 0.97-5.02; p = 0.013), in patients with moderate or high score for NDRG-1 (p = 0.005), and in those with high-expression for PHLDA-3 (HR: 1.94; 95%CI: 1.05,3.6; p = 0.036). A significant difference in OS was observed based on NDRG-1 score (p = 0.013). In multivariate analyses, ki-67 (HR: 2.45; 95% CI: 1.20-5.01; p = 0.01) and IPS (HR: 2.68; 95% CI: 1.60,4.49; p = 0.00018) were independent prognostic factors for DFS, while age (HR: 7.67; 95% CI: 2.14,27.45; p = 0.0017) and IPS (HR: 2.67; 95% CI: 1.11, 6.41; p = 0.03) were independent prognostic factors for OS. HCI for the multivariate DFS and OS models were 0.796 and 0.788, respectively. Conclusions: Our IPS is a useful prognostic biomarker for recurrence and survival in patients following resection for PanNET. Prospective studies are warranted to validate our findings and determine its role for patients’ selection to neo/adjuvant treatments