tbuckley/cabot-search huggingface dataset:
Loss of BAP1 and PBRM1 protein expression and its association with clear cell renal cell carcinoma-specific survival.
Authors: Richard Wayne Joseph, Payal Kapur, Daniel Serie, Jeanette Eckel-Passow, Thai Huu Ho, James Brugarolas, Alexander S. Parker
Journal: Journal of Clinical Oncology (2014)

414 Background: While mutations in PBRM1 (~40%) and BAP1(~10%) are associated with clinical outcomes and pathologic features in clear cell renal cell carcinoma (ccRCC), the impact of protein expression of these genes remains unknown. Herein, we quantify PBRM1/BAP1 protein expression in a large cohort of patients with localized ccRCC and associate expression with cancer-specific survival (CSS) and pathologic features. Methods: We utilized the Mayo Clinic Renal Registry and identified 1,416 patients who underwent nephrectomy to treat clinically localized ccRCC between 1/3/1990 and 4/14/2009. We used immunohistochemistry (IHC) to detect PBRM1/BAP1 expression, and a central pathologist blinded to the outcomes scored tumors as either positive or negative. Tumors with heterogeneous or equivocal staining were excluded from this analysis. We generated Cox proportional hazard regression models for associations with ccRCC-SS, and we employed Mann-Whitney U tests for associations with pathologic features. Results: Of the 1,416 samples, 1,232 (87%) were PBRM1/BAP1 positive or negative, 163 (11%) had heterogeneous staining, and 21 (1%) could not be assessed. The distribution and association of PBRM1/BAP1 phenotypes with clinical outcomes are listed in the table below. PBRM1+/BAP1+ tumors have the best CSS, and PBRM1-/BAP1- have the worst. In addition, PBRM1/BAP1 expression strongly associated with the tumor size, stage, grade, and tumor necrosis (p&lt;0.0001). Conclusions: This study is the first and largest to quantify PRBM1/BAP1 protein expression in ccRCC tumors. We were able to quantify PBRM1/BAP1 through IHC in the vast majority of tumors (87%), and PRBM1/BAP1 expression strongly associates with both CSS and pathologic tumor characteristics. Our data confirms our previous findings of the importance of PRBM1/BAP1 in the molecular pathogenesis of ccRCC. [Table: see text]
Randomized phase II studies comparing pathological responses observed on colorectal cancer metastases resected after preoperative treatment combining bevacizumab or cetuximab with FOLFOX or FOLFIRI.
Authors: Marc Van Den Eynde, Marie-Laure Castella, Jean-Pascal H. Machiels, Yves Humblet, Jean-Luc Re Canon, Ghislain Houbiers, Gauthier Demolin, Lionel A. D'Hondt, Jean-Charles Coche, Daniel Van Daele, Thierry Delaunoit, Jean Charles. Goeminne, Gabriella Beniuga, Geraldine Pairet, Christine Sempoux, Anne Jouret-Mourin, Aline Van Maanen, Javier Carrasco
Journal: Journal of Clinical Oncology (2015)

TPS795 Background: Even if the use of targeted therapies combined with chemotherapy has demonstrated increase response rate and survival benefit in non resectable metastatic colorectal cancer (mCRC), the administration of these combinations in frontline resectable disease is source of debate and optimal association is still unclear. Based on a retrospective analysis, we previously reported thatthe chemotherapy partner combined with VEGF or EGFR inhibitors influenced pathological responses (pR) on the resected colorectal cancer metastases (CRCM) with a significant advantage for oxaliplatin with anti-VEGF or irinotecan with anti-EGFR combinations. We aimed to design 2 parallel studies (BEV-ONCO, CET-ONCO) to prospectively precise optimal combination between oxaliplatin and irinotecan with bevacizumab or cetuximab before CRCM resection. Methods: The 2 studies are open label randomized multi-centric trials and concern mCRC patients with resectable disease in whom a preoperative treatment is considered. The primary objective is to assess the CRCM pR rate according the Tumor Regression Grade classification (Rubbia-Brandt) after allocated preoperative treatment (bevacizumab combined with FOLFOX vs. FOLFIRI without consideration of RAS/BRAF for BEV-ONCO trial (EUDRACT 2012-005376-34) and cetuximab associated with FOLFOX or FOLFIRI only for RAS/BRAF wild type tumor for CET-ONCO trial (EUDRACT 2012-005249-19)). According investigator’s choice, patient will received 3 to 6 treatment cycles before CRCM resection. Patient’s survival, safety, surgical complications and treatment associated liver-toxicity are secondary end-points. Up to 60 patients (30 per treatment group) will be randomised in each study (power: 80%, type I error of 5% to detect a difference in proportion of pR rate between FOLFOX or FOLFIRI association of 0.40). Formal comparison will not be done across studies. Translational research projects are ongoing (CRCM immune response, tumour specific genetic rearrangements as new specific biomarkers). Clinical trial information: NCT01858649 (BEV-ONCO); NCT01858662 (CET-ONCO). Clinical trial information: NCT01858649 (BEVONCO) NCT01858662 (CETONCO).
Immune cell repertoire in patients with indolent metastatic renal cell carcinoma.
Authors: Hui Zhu, Pat A. Rayman, Paul Elson, Sarah Rapp, Jorge A. Garcia, Robert Dreicer, Timothy D. Gilligan, Dale Randall Shepard, James Finke, Brian I. Rini
Journal: Journal of Clinical Oncology (2013)

429 Background: Immune dysfunction is well documented in renal cell carcinoma (RCC) patients and likely influences tumor progression. An ongoing prospective trial of observation in metastatic RCC patients prior to systemic therapy is investigating circulating immune cell populations. Methods: Asymptomatic patients with low volume metastatic disease are enrolled and followed until starting initial systemic treatment. Peripheral blood specimens are collected at the time of enrollment and again at the time of initiating therapy. The immune parameters measured include CD3+ and CD4+ INF-γ producing T cells (INF-γ+ T), CD4+CD25+FoxP3+ regulatory T-cells (Treg), and CD33+HLADr-CD15+CD14- neutrophilicmyeloid-derived suppressor cells (N-MDSC). Similar immune parameters were recorded for treatment-naïve patients prior to immediate systemic therapy and healthy volunteers on separate IRB-approved protocols. Results: 25 patients are enrolled in the study, of whom 14 started systemic therapy and had immune function analyzed for this report. Patient characteristics included 100% male, median age 74. 13 patients were favorable or intermediate risk by both MSKCC and Heng prognostic criteria; one patient was poor-risk. The median observation period was 13.9 months. The median tumor burden at the time of enrollment was 3.6 cm, which increased 38% during the observation period. As shown in the table below, the observation group had lower levels of Tregand N-MDSC, and higher levels of INF-γ+ T compared to the treatment group. In contrast, the observation group’s INF-γ+ T was similar to that of controls although N-MDSC was elevated. Conclusions: Metastatic RCC patients with indolent disease have low levels of Tregand N-MDSC, and a relatively preserved immune cell repertoire compared to patients requiring immediate therapy. [Table: see text]
Fast-tracking palliative care consults: Pilot implementation of National Comprehensive Cancer Network (NCCN) palliative care screening and referral guideline.
Authors: P. A. Glare, M. K. Plakovic, Y. Griffo, N. Moryl, S. M. Stabler, R. Tickoo, S. Norona, B. Stenson, B. Egan, H. T. Thaler, D. P. Kelsen
Journal: Journal of Clinical Oncology (2011)

e19636 Background: The NCCN PC Guideline recommends screening all patients for PC needs at clinically relevant intervals and to call a PC consult when referral criteria (RC) are met. Because most of the care of gastrointestinal oncology (GIO) patients is ambulatory, hospitalization is an appropriate time to rescreen. The aim of this quality improvement project was to evaluate using the guideline on a hospitalist-led GIO inpatient unit of a comprehensive cancer center (CCC). Methods: From 11/1/10 to 1/28/11, inpatient nurses screened patients admitted to one GIO Service on a floor of Memorial Hospital the day after admission. PC consults were automatically performed on those meeting the RC. Definitions were developed to categorize consults as “simple” (manageable by the primary team) or “complex” (requiring a full consult). Results: Of 127 admissions, 104 (87%) were screened (<5 minutes/patient), 64 (63%) met the RC and 35 consults were done on 33 patients: 20M, 13F, median age 60, with upper GI (12), pancreato-biliary (10) and colorectal (10) primaries. PC problems elicited at consultation are shown in the Table. Median number of PC problems per case was 3. Recommendations by PC consultant were: disposition planning 15, education 14, pain management 12, psychosocial support 12, request consultation 10, other symptom management 9, clarify code status 8, spiritual support 7, identify health care proxy 4, family conference 3, order investigations 2. In 11, all PC needs were deemed “simple”, i.e., manageable by the hospitalists leading this team, who develop substantial skills in handling simple PC issues in hospitalized GIO patients. Outcomes and impact of the consultations will be evaluated. Conclusions: Using the NCCN Guideline, nurses were able to rapidly screen hospitalized GIO patients for PC issues. But with a consult indicated in 63% patients, the current RC may be too sensitive to mandate in a hospitalist-led inpatient environment in a CCC. The guideline needs more evaluation before widespread implementation. Problem Simple Complex Total Accepting options are limited 11 13 24 Nonpain symptom 16 7 23 Pain 12 7 19 Psychosocial or spiritual issue 7 10 17 Disposition plan 7 6 13
Clinical features in surgically treated patients with small cell lung cancer: Risk of brain metastasis and possible role of prophylactic cranial irradiation.
Authors: Y. Horio, S. Ishikawa, Y. Yatabe, J. Shimizu, K. Yoshida, T. Fukui, S. Ito, Y. Hasegawa, T. Mitsudomi, T. Hida
Journal: Journal of Clinical Oncology (2010)

e17532 Background: Prophylactic cranial irradiation (PCI) can improve both disease- free and overall survival in selected patients with small cell lung cancer (SCLC). Although PCI in early LS-SCLC patients who are surgically resected and treated with adjuvant chemotherapy is considered to be a reasonable treatment option, the precise role of PCI for those patients remains unclear. Methods: The records of 29 patients with SCLC undergoing curative surgery at our institution between 1995 and March 2008 were retrospectively reviewed. Clinical information, pathologic features and radiographic data obtained during a 14-year treatment period were collected to assess patterns of relapse and overall survival. Results: Nine patients underwent induction chemotherapy or chemoradiotherapy. Fourteen patients (48%) had pathologic stage I disease, 7 patients (24%) had pathologic stage II disease and 7 patients (24%) had pathologic stage III disease. Twenty patients underwent adjuvant chemotherapy or chemoradiotherapy. One patient received PCI. There were a total of 13 deaths and 8 were disease-related. The 5-year survival rate was 64.3% for p-stage I, 27.8% for p-stage II/III, respectively. Ten (34%) of the 29 patients had a relapse. Two patients had a local relapse alone, one patient had a combined local and distant relapses, and seven patients had distant metastases alone as their first site of failure. Brain metastases as first recurrence occurred in 4 patients (28.6%) of 14 patients with p- stage II/III. Conclusions: Surgically resected patients with p-stage II/III SCLC might be good candidates for PCI. No significant financial relationships to disclose.
A phase I study of ASG-5ME, a novel antibody-drug conjugate, in pancreatic ductal adenocarcinoma.
Authors: Andrew L. Coveler, Daniel D. Von Hoff, Andrew H. Ko, Nancy Cherry Whiting, Baiteng Zhao, Brian M. Wolpin
Journal: Journal of Clinical Oncology (2013)

176 Background: ASG-5ME is an antibody-drug conjugate (ADC) targeting SLC44A4, an ion transporter expressed on &gt;90% of pancreatic ductal adenocarcinoma (PDA). ASG-5ME comprises a fully human antibody covalently linked, with a protease-cleavable linker, to the microtubule-disrupting agent monomethylauristatin E (MMAE). Upon binding to SLC44A4 and internalization, MMAE is released by proteolytic cleavage, binds to tubulin, and subsequently induces cell cycle arrest and apoptosis. Selective targeting of tumor cells by an ADC represents a novel therapeutic approach for patients (pts) with PDA. Methods: This phase I, dose-escalation, multicenter study investigated the safety, PK, and antitumor activity of ASG-5ME in pts with metastatic PDA. Patients received ASG‑5ME IV in cohort-specific doses on Days 1, 8, and 15 of 28-day cycles until disease progression or unacceptable toxicity. Results: Thirty-five pts (median age 63 yrs, range 32-73) were treated at doses of 0.3 to 1.5 mg/kg. All pts had metastatic PDA and ECOG status 0-1. Thirty-three pts (94%) had previously received chemotherapy for metastatic disease or in the perioperative setting; the median number of prior therapies for metastatic PDA was 3 (range 1-6; n=27). The maximum tolerated dose (MTD) was exceeded at the 1.5 mg/kg dose level, with 1 DLT of Grade 4 GI hemorrhage and 4 pts experiencing non-DLT Grade 3 or 4 neutropenia. Thus, 1.2 mg/kg was identified as the MTD and expanded (N=18). The most common AEs observed at the MTD were fatigue (50%), vomiting (44%), decreased appetite (39%), nausea (33%), and abdominal pain (33%); Grade 3 or 4 toxicities at the MTD included fatigue (28%), abdominal pain (22%), vomiting (17%), and neutropenia (17%). Antitumor activity was observed: 1 pt achieved an unconfirmed PR and 12 pts achieved SD. Five patients (14%) had reductions in CA19-9. Serum ASG-5ME exposures were approximately dose proportional. Of 23 pts with archived biopsies available for IHC analysis, 100% expressed SLC44A4 and 15 pts (65%) had high expression. Conclusions: ASG-5ME treatment was generally well tolerated in metastatic PDA pts, with preliminary evidence of antitumor activity. Further study of ASG-5ME in SLC44A4-expressing malignancies is warranted. Clinical trial information: NCT01166490.
Neutrophil-to-lymphocyte ratio for predicting palliative chemotherapy outcomes in advanced pancreatic cancer patients.
Authors: Peng Xue, Masashi Kanai
Journal: Journal of Clinical Oncology (2014)

186 Background: Several previous studies reported neutrophil-to-lymphocyte ratio (NLR) could be a promising prognostic factor for patients with cancer. We aimed to determine the prognostic value of NLR in patients with advanced pancreatic cancer (APC) following palliative chemotherapy. Methods: We retrospectively reviewed 253 consecutive APC patients receiving palliative chemotherapy between January 2006 and December 2012. We classified the patients according to the pretreatment NLR values (≤5 or &gt;5) into two groups and investigated the difference in treatment outcomes, including time to treatment failure (TTF) and overall survival (OS); and also analyzed the impact of NLR kinetics after one cycle of chemotherapy on the treatment outcomes. Results: A total of 213 patients had pretreatment NLR values of ≤5 (group A), while 40 patients had an NLR of &gt;5 (group B). TTF and OS were significantly shorter in group B than in group A (3.1 vs. 6.0 months and 8.8 vs. 12.8 months, respectively). After adjustment for putative prognostic factors, including distant metastasis, status of recurrent/unresectable disease, pretreatment carbohydrate antigen 19-9 levels, carcinoembryonic antigen levels, and C-reactive protein levels, using the Cox regression model, elevated pretreatment NLR remained an independent poor prognostic factor for OS (hazard ratio, 1.95; 95% confidence interval, 1.29–2.95; P &lt;0.01). In addition, patients in group B whose NLR dropped to ≤5 before the second cycle of chemotherapy showed longer TTF and OS compared with those whose NLR remained at &gt;5. Conclusions: Our results support the idea that NLR can be a promising prognostic and predictive marker for APC patients receiving palliative chemotherapy.
Long Term Prospective Follow-Up after Treatment Intensification in Pediatric Sickle Cell Patients: Comparative Effects of Transfusion Program (TP), Hydroxyurea (HU) or Stem Cell Transplant (SCT) on Annual Check-Ups.
Authors: Francoise Bernaudin, Emmanuelle Lesprit, Lena Coïc, Cécile Arnaud, Emmanuelle Fleurence, Suzanne Verlhac, Christophe Delacourt
Journal: Blood (2005)
Prognostic factors of long-term survival in patients with acute myeloid leukemia after allogeneic or autologous stem cell transplantation.
Authors: L. Wang, C. Corona, X. Nie, L. Mejias, S. j. Hou, R. Mullaney, K. M. Ward, D. L. Topolsky, M. Styler, P. A. Crilley
Journal: Journal of Clinical Oncology (2011)

6594 Background: The purpose of this study is to provide a long-term survival analysis for patients with acute myeloid leukemia (AML) after allogeneic or autologous stem cell transplantation (SCT). Methods: The patients included were 210 AML patients treated at Hahnemann University Hospital from 1980 through 2004. End points were overall survival (OS) and progression-free survival (PFS) calculated by Kaplan-Meier method. Results: We showed a statistically significant long-term survival advantage when transplantation was performed in the first complete remission (CR1) as opposed to subsequent remissions or relapse (median OS: 97 months vs 17 months vs 3 months for allogeneic SCT, and 38 months vs 13 months vs 4 months for autologous SCT, p<0.001). Compared to autologous SCT, there was a 60% improvement in median OS for patients treated with allogeneic SCT in CR1 (p=0.025). Among AML subtypes, a trend toward improved survival was noted for M2 following allogeneic, but not autologous, SCT. The median OS was not reached for M2 after 20 years follow-up (P<0.08). Although severe graft versus host disease (GVHD) was associated with early transplant-related mortality, occurrence of grade I and II acute or limited chronic GVHD had favorable long-term survival. On the contrary, veno-occlusive disease (VOD) of the liver had little impact on long-term survival. We also compared outcomes of overall survival for patients who received different pre-transplant conditioning regimens after allogeneic SCT. Compared to BU/CY4 (busulfan 16mg/kg plus cyclophosphamide 200mg/kg given over 4 days) and BU/CY/VP (busulfan 16mg/kg, cyclophosphamide 120mg/kg, VP16 40mg/kg), BU/CY2 (busulfan 16mg/kg plus cyclophosphamide 120mg/kg given over 2 days) was associated with a significantly improved long-term survival (59.6% vs 27.3% vs 15.5% at 10 years, P< 0.001). Conclusions: These results demonstrated a superior overall survival in AML patients who received allogeneic SCT in CR1 compared to autologous SCT at the same remission status. AML subclasses, pre-transplant conditioning regimens, and grade I/II GVHD are additional factors contributing to long-term survival after allogeneic SCT.
Use of Fluid-Ventilated, Gas-Permeable Scleral Lens (SL) for Management of Severe Keratoconjunctivitis Sicca Secondary to Chronic Graft-Versus-Host Disease.
Authors: Kikuchi Takahide, Pablo Miguel Parker, Michael Wu, Paul A. Carpenter, Barbara Stehr, Perry Rosenthal, Paul J. Martin, Stephen J. Forman, Mary E.D. Flowers
Journal: Blood (2006)
Barriers to clinical practice guidelines adherence in the community oncology setting.
Authors: L. M. Shah, T. V. Carino, M. Hanger, L. G. Barnes, A. S. Weinstein
Journal: Journal of Clinical Oncology (2011)

e19687 Background: Clinical practice guidelines (CPGs) are an important information source for physicians as they integrate evidence into routine clinical care. However, the use of CPGs may vary by physician and specialty. Methods: The Association of Community Cancer Centers and Avalere Health designed a survey to identify how community oncologists use CPGs, focusing on: physicians’ perceptions of guidelines, which guidelines they follow, and barriers to guideline adherence. The online survey contained 45 items and was closed in June 2010. Results were tabulated and analyzed. Results: Thirty-six physicians from distinct practices responded. Physicians were likely to have more than 25 years experience (74%) and to treat multiple cancer types (47%). The majority worked in community hospitals (56%), cancer clinics (36%), and private practices (28%). Overall, 94% of physicians reported following CPGs, with NCCN (94%) and ASCO (69%) being preferred sources. However, physicians reported barriers to following CPGs in nearly one fifth (16%) of patient cases. Important barriers included limited time (44%) and limited access to CPGs at the point of care (39%). Common reasons physicians cited for not following guideline recommendations was that they were too rigid for a particular patient (53%) or were not appropriate in a given clinical situation (62%). Notably, the majority of physicians (94%) reported that their practices have created their own guidelines or protocols at times, with one quarter (25%) doing so regularly. Conclusions: Despite agreeing that CPGs are important for delivering high quality patient care, physicians report barriers to CPG adherence and do not consider recommendations appropriate for all patients. Furthermore, many practices are creating their own CPGs, which may undermine a fundamental reason for CPGs: increased standardization of care. Further research on individual physician and practice-level deviation from established CPGs is needed.
A personalized sunitinib (S) first-line approach in elderly patients with metastatic renal cell carcinoma (mRCC).
Authors: Maria Cossu Rocca, Roberto Iacovelli, Elena Verri, Claudia Crescio, Gaetano Aurilio, Serena Detti, Daniela Cullura, Franco Nole
Journal: Journal of Clinical Oncology (2016)

602 Background: About 24% of mRCC are older than 74 yo. S is a well-established first-line therapy for mRCC with a specific toxicity profile requiring a dose reduction in 30% of pts. Actually few data are available in the Literature about its use in patients &gt; 75 yo especially as regards efficacy and cost effectiveness of tailored approaches. Methods: The primary end-point of this prospective single arm study, is to assess if a personalized approach is able to decrease the rate of dose reduction to 8% after the first cycle of S.. 19 pts have been estimated to be necessary to explore this hypothesis. Secondary objectives were the safety, treatment duration (TD) and overall survival (OS). Personalized approach was defined as the starting dose of S choose by the medical oncologist based on performance status (PS ECOG) and number of comorbidities. Results: From 2007 to 201421 pts were enrolled. The median age was 77.9 yrs (IQR 74.1-82.1). Seventy-five % had a clear cell carcinoma, 20% had a metastatic disease at diagnosis and 60% had &gt; 2 sites of metastasis. All pts had PS ECOG ≥ 1 and 50% suffered from &gt; 2 comorbidities. 43% were good, 52% intermediate and 5% poor prognosis by IMDC criteria. 3 pts (14%) started S at 50 mg/d, 9 pts (42%) at 37.5 mg/d and 9 pts (42%) started with 25 mg/d. All pts received S with the 4/2 schedule. The dose reduction after the first cycle was 28%. The reason was always toxicity, but no treatment interruption occurred. No pts starting at 25 mg had dose modification. The main toxicity requiring dose reduction was G3 anemia in 1pt, G3-4 thrombocytopenia in 3 pts and G3 leuconeutropenia in 3 pts . The median TD was 11.9 mos (95%CI, 6.5-17.3). The median OS was 33.3 mos (95%CI, 26.1-40.6). Conclusions: This study shows that a personalized starting dose is not able to decrease the rate of dose reduction at first cycle. Nonetheless a personalized strategy does not affect negatively the OS of elderly pts. Actually in elderly pts a disease stabilization without acute adverse events, could be considered an adequate goal. A well tolerated therapy could also be cost effective because part of health cost, especially for elderly pts, derives from their hospitalization for adverse events. Further data are required.