tbuckley/cabot-search huggingface dataset:
Development of nomogram to predict renal function outcome after laparoscopic partial nephrectomy: Japanese multi-institutional study including 915 patients.
Authors: Hideo Saito, Tadashi Matsuda, Kazunari Tanabe, Akihiro Kawauchi, Toshiro Terachi, Ken Nakagawa, Masatsugu Iwamura, Masanobu Shigeta, Seiji Naito, Akihiro Ito, Yoichi Arai
Journal: Journal of Clinical Oncology (2013)

e15576 Background: Chronic kidney disease (CKD) is an independent risk factor for death from all causes. However Japanese individuals tend to have a different lifestyle, including diet and other behavior, than Western individuals and in Japanese some studies show a lower prevalence of obesity and atherosclerosis. To evaluate longitudinal change in renal function after laparoscopic partial nephrectomy (LPN) with renal tumors, we investigate predict risk factor which affect a decrement of renal function. Methods: A nation-wide survey was performed by the LPN study group under the support of Japanese Society of Endourology. Of the 228 insitutes, 63 (28%) insitutes had more than 10 LPN experience. Between Dec 1998 and Dec 2008, 1,375 Japanese patients underwent LPN. Patients with solitary kidney, preoperative eGFR below 45ml/min/1.73m 2 were excluded from analysis. Thus, 915 patients were enrolled in this study. Multivariate analysis was performed examining factors associated with the development of de novo eGFR&lt;45 and 60. Results: Patient charcteristics: median age 60 yrs (IQR 50-69), male/female 672/243, hypertension 307 (34%), diabetes mellitus 149 (16%), hyperlipidemia 115 (12%), median BMI 23.8 (IQR 22-26), mean ASA score 1.6±0.6., median tumor size was 2.1 cm (IQR 1.7–2.8), median preoperative eGFR 74 (IQR 64-86). Pedicle clamping was done in 674 cases (73%). The 1-year probability of new onset of an eGFR less than 60 and 45 was 20.0% and 5.6%, respectively. A multivariate model revealed that age, tumor size and preoperative eGFR are independently predictive of de novo eGFR&lt;45. Nomogram was developed based on a multivariate logistic regression model. The area under the ROC curve for de novo eGFR&lt;45 was 0.930. Conclusions: Compared with radical nephrectomy, LPN could preserve renal function. But, even in Japanese, patients undergoing LPN had high comorbidity and 20% of patients developed de novo eGFR&lt;60. We developed novel predictive models for CKD after LPN. This nomogram provides important implications in clinical decision making regarding treatment options or follow-up strategy.
Anti-EGFR treatment for EGFR-amplified gastroesophageal adenocarcinoma.
Authors: Steven Brad Maron, Lindsay Alpert, David Xu, Rachel Rendak, Emily O'Day, Namrata Setia, Daniel V.T. Catenacci
Journal: Journal of Clinical Oncology (2017)

60 Background: Gastroesophageal cancer (GEC) is a global health problem. Multiple phase III anti-EGFR trials of unselected metastatic GEC patients (pts) were negative, yet subset analyses suggested potential benefit in pts with EGFR amplification (amp). We sought to quantify the incidence of EGFR amp in metastatic/recurrent GEC pts compared to the locally advanced TCGA rate, treat them with EGFR antagonists, quantify response/duration, and assess for mechanisms of action and resistance (MOA, MOR). Methods: 106 stage IV GEC pts in any therapy (tx) line (L) were prospectively screened for EGFR amp between 9/1/14-8/31/16 at a single site using tumor next generation sequencing (NGS). EGFR amp samples were then assessed by FISH, immunohistochemistry (IHC) and mass spectroscopy (MS) to confirm. Pts received 1L ABT-806 (1/4) or 2L+ cetux (3/4) monoclonal anti-EGFR antibodies, in combination with chemotherapy if 1L or 2L (2/4), or as monotherapy for 3L+ (2/4). Pts were followed for response (ORR) and disease control (DCR). Pre and post-treatment NGS, serial ctDNA, and EGFR/PD-L1 FISH/IHC/MS were obtained to monitor for MOA and MOR to tx. Results: Six (5.7%) pts harbored EGFR amp tumors with copies/cell ranging 54-167. Four eligible pts received &gt;1 dose of tx with monoclonal anti-EGFR therapy: 1 FOLFOX-ABT-806 (1L), 1 FOLFIRI-cetux (2L), and 2 cetux alone (3L, 4L); ORR was 100% (4/4) by RECIST, respectively (-70%, -65%, -77%, -43%). All 3 cetux treated pts developed classic rash, which disappeared when/if progression (2/3). The 4-month DCR was 75% (3/4). No pts showed PD-L1 staining pre/post therapy. Upon progression, the 2L pt acquired de novo PTEN exon 6 deletion after 10 months, while basal NRAS mutated and HER2 amp ctDNA clones had expanded in the 4L pt after 4 months of monotherapy. Conclusions: EGFR amp incidence was similar to TCGA. Despite large negative trials with EGFR antagonists for GEC, EGFR amp predicted benefit (100%) from anti-EGFR tx, including monotherapy in 50%, albeit until various resistance mechanisms emerged, including HER2, RAS, and PTEN/AKT pathway activation. No PD-L1 expression was observed pre/post treatment, consistent with our previous data showing that EGFR-amplified cases trend towards a ‘non-T cell-inflamed’ phenotype. Clinical trial information: NCT01416714 / NCT02213289.
Different safety profiles of first-line bendamustine-rituximab (BR), R-CHOP, and R-CVP in an open-label, randomized study of indolent non-Hodgkin lymphoma (NHL) and mantle cell lymphoma (MCL): The BRIGHT study.
Authors: David MacDonald, Richard van der Jagt, John M. Burke, Brad S. Kahl, Peter Wood, Tim E. Hawkins, Mark Hertzberg, Yiu-Lam Kwan, David Simpson, Michael Craig, Kathryn S. Kolibaba, Samar Issa, Regina Clementi, Doreen M. Hallman, Mihaela C. Munteanu, Ling Chen, Ian Flinn
Journal: Journal of Clinical Oncology (2013)

8565 Background: The BRIGHT study demonstrated that first-line BR was non-inferior to R-CHOP/R-CVP in terms of complete remission rate in indolent NHL and MCL. This is the first detailed analysis of the safety and tolerability of the study regimens. Methods: Patients were preselected for R-CHOP or R-CVP, and then randomized to 6-8 cycles of BR (28-d cycle) or the preselected standard regimen (21-d cycles). BR dosing was bendamustine 90 mg/m 2 /d as a 30-min infusion on days 1 and 2 plus rituximab 375 mg/m 2 given before bendamustine on day 1. Colony stimulating factors (CSFs) and antiemetics were given per local standards. Results: In patients preselected for R-CHOP, 103 received BR and 98 R-CHOP. In patients preselected for R-CVP, 118 received BR and 116 R-CVP. For all regimens, ≥ 88% of patients received the planned 6 cycles. Main differences in adverse events (AEs), all grades, are shown in the Table. Incidence of grade 3/4 AEs was 69% for R-CHOP vs 56% BR, and 50% for R-CVP vs 56% BR. Grade 3/4 drug hypersensitivity, neuropathy, and rash were infrequent. Antiemetic use was similar between groups except use of aprepitant as an adjunct to 5-HT3 antagonists was higher with R-CHOP (23% [19% in cycle 1]) than BR (9% [2%]) or R-CVP (3% [2%]). CSF use was higher with R-CHOP (61%) than BR (29%) or R-CVP (27%). Analyses of event prevalence over the treatment period and by region will also be presented. Conclusions: BR, R-CHOP, and R-CVP have significantly distinct AE profiles. More nausea, vomiting, and hypersensitivity occurred with BR while more constipation, neuropathy, and alopecia occurred with RECHOP/R-CVP. Support: Teva BPP R&amp;D, Inc. Clinical trial information: NCT00877006. [Table: see text]
Observational cross-sectional study to evaluate the prognostic factors influencing the selection of bevacizumab combined with chemotherapy in patients with HER2-negative metastatic breast cancer in routine clinical practice. ONCOSUR-AVALOX study.
Authors: Luis Manso, Ramon Perez-Carrion, Jose Ignacio Chacon Lopez-Muniz, Andres Garcia Palomo, Elena Galve Calvo, Rosa M. Llorente, Javier Cassinello, Gustavo Catalan, Cristina Llorca, Maria Dolores Torregrosa, Inaki Alvarez, Isabel Gallegos Sancho, Esperanza Blanco, Mauro Oruezabal, Xabier Mielgo Rubio, Maria Jose Garcia Lopez, Blanca Hernando, Santos Enrech, Miguel Angel Lara, Hernan Cortes-Funes
Journal: Journal of Clinical Oncology (2012)

e11074 Background: Combining bevacizumab (BEV) with chemotherapy (CT) improves survival in HER2-negative metastatic breast cancer (MBC). We investigated the influence of age, ECOG, hormonal status, number of sites and location of metastases and patient decision on the selection of BEV combined with CT in MBC. Methods: Observational cross-sectional multicenter study in pts with HER2-negative MBC who have received first-line CT with BEV. Results: From November 2010 to November 2011, 124 pts were included: median age 51 (45-64) yr; ECOG: 0=50%; 60% pre-menopausic; 23% triple-negative (TN); 77% hormone receptor-positive (HR+). Metastatic disease: ≥3 sites=42% (TN: 32%; HR+: 45%); location: 44% bone, 35% lung, 30% liver. Most frequent BEV-based combinations were paclitaxel/BEV (53%) and docetaxel/BEV (14.5%); median no. of CT cycles: 6 (5-8). A disease-free survival (DFS) ≥12 months was achieved by 73%; TN: 68%; HR+: 76%. Overall response rate (ORR) was 58%: 51% partial response (PR), 7% complete response (CR); 28% stable disease (SD) and 10% disease progression. TN: ORR 44% (40% PR), clinical benefit 80% (36% SD); HR+: ORR 62% (54% PR), clinical benefit 87% (25% SD). 58% presented at least one toxicity, mainly grade 1-2; 26% BEV-related: only 3 (2.4%) grade 3 toxicities; no grade 4. Receiving adjuvant hormonal therapy was associated to DFS ≥12 months (p&lt;0.05). ER+ tumors (OR: 0.215; 95% CI: 0.08-0.56; p=0.002) and one metastatic site, vs. ≥3 sites (OR: 0.309; 95% CI: 0.12-0.83; p=0,020) were independent factors associated with the selection of paclitaxel-BEV therapy in the overall population (TN or HR+). Metastases in the liver were significantly related to paclitaxel-BEV administration (p&lt;0.01). Conclusions: Our findings suggest that first-line CT with BEV is an active and tolerable treatment option for pts with TN and HR+ MBC. ER+ tumors and a single metastatic site were identified as independent factors for the selection of a paclitaxel-BEV therapy. The presence of metastases in the liver was significantly associated to the administration of a paclitaxel-BEV regimen.
Soft tissue sarcomas in the general and referral population: The University of Maryland Medical Center experience.
Authors: Michael Nathenson, Robert Aaron Nathenson, Nader Hanna, William Regine, Vishal Bhatnagar, Michael David Chuong, James Snider, Edward A. Sausville
Journal: Journal of Clinical Oncology (2015)

e21525 Background: Soft tissue sarcoma (STS) is a rare diagnosis, with approximately 13,000 cases in the United States per year, and a 50% 5-year overall survival (OS). The objective of this study was to review the University of Maryland Medical Center’s (UMMC) experience in the treatment of soft tissue sarcomas. The specific focus of the study was to discern differences in survival relatable to patient (Pt) (sex, race, age) and tumor (grade, size, stage, sarcoma location, and histology) characteristics, and the treatment (surgical resection, radiation and chemotherapy) chosen. Methods: With IRB approval, a de-identified database was constructed of all patients (Pts) diagnosed with sarcoma and treated at UMMC between 2000 and 2013. Of 548 sarcoma Pts there were 331 STS that constituted the study population, 45 metastatic on diagnosis. We used Kaplan-Meier methods to estimate OS. Results: The 5-year OS for all Pts was 53.1%. The UMMC population consisted of 60.7% Caucasians and 32% Blacks, with no difference in survival by race at 5 years, Caucasian 52.2%, Black 56.6% p = 0.51. Improved survival was influenced by younger age, lower grade, smaller size, and early stage tumors, tumor location, and sarcoma histologic subtype with best outcomes (liposarcoma, fibrosarcoma) and worst (undifferentiated pleomorphic sarcoma, angiosarcoma). Neither adjuvant chemotherapy (35 Pts), neoadjuvant/adjuvant radiation therapy (150 Pts), nor resection extent improved OS, while the number of resections a Pt received did correlate with improved survival at 5 years 55.9% for 1 resection (168 Pts), 78.9% for 2 resections (38 Pts), 6.5% for no resection (31 Pts) p < 0.001. Pts who underwent palliative surgery, defined as resection of local recurrence or metastatectomy, had improved survival at 5 years 56.6% vs 19.1% p < 0.001. Conclusions: In the UMMC experience, with a substantial black Pt population, race was not an important predictor for OS. These results support the strategic use of successive multiple resections where clinically feasible, and emphasize that those Pts able to undergo palliative surgery attain superior survival. In the future, the biological features of subsets of these Pts will be important to define.
Bortezomib and capecitabine in patients with metastatic breast cancer previously treated with taxanes and/or anthracyclines: Final results of a phase I/II study
Authors: P. Schmid, A. Regierer, P. Kiewe, W. Schippinger, R. Greil, S. Lehenbauer-Dehm, N. Niederle, W. Freier, H. Van de Velde, K. Possinger, D. Kuehnhardt
Journal: Journal of Clinical Oncology (2007)

1072 Background: Capecitabine has shown substantial activity in taxane and/or anthracycline pretreated breast cancer patients. Bortezomib, a 26S proteasome inhibitor, has been shown to increase sensitivity to chemotherapy. This phase I/II trial was initiated to evaluate the combination of capecitabine and bortezomib in heavily pretreated patients with metastatic breast cancer. Methods: Patients with metastatic breast cancer and prior taxane and/or anthracycline therapy were treated with bortezomib (1.0–1.3 mg/m 2 ; days 1, 4, 8 &amp; 11) and capecitabine (1,500–2,500 mg/m 2 , days 1–14) in 3-weeks intervals for up to 8 cycles. Primary endpoints were to determine the optimal doses for the combination (phase I) and the tumor response rate (RR) (phase II). Secondary endpoints included safety, time to progression (TTP), duration of response (DR), and overall survival (OS). Results: A total of 35 patients were enrolled and 29 patients were assessable for response. The majority of patients had received 2 or 3 lines of chemotherapy (69% and 14%, respectively) prior to the study. The maximum tolerated doses (MTD) were bortezomib 1.3 mg/m 2 and capecitabine 2500 mg/m 2 . Dose limiting toxicities were Grade 3 stomatitis in 1 out of 6 patients at 1.0/2,000 and Grade 3 diarrhea in 1 out of 6 patients at 1.3/2,500. Myelosuppression was low. Non-hematological toxicities were generally mild to moderate with no G4 toxicity being observed. Most common side effects were thrombocytopenia (Grade 3/4 27% of patients), diarrhea (18%), hand-foot syndrome (12%), peripheral neuropathy (12%), leucopenia (9%) and asthenia (9%). The overall RR was 17.2% and an additional 31% of patients had stable disease (31%; 4 unconfirmed). In the 21 patients treated at the MTD, RR was 17.6% and 47% of patients had SD. Median TTP and OS were 3.5 months (95% CI 1.9–4.4) and 7.5 months (95% CI 5.6–14.6), respectively. Median DR was 4.4 months. Conclusions: The combination of bortezomib and capecitabine is well tolerated and has moderate antitumour activity in heavily pretreated breast cancer. [Table: see text]
Effects of cediranib, a VEGF signaling inhibitor, in combination with chemoradiation on tumor blood flow and survival in newly diagnosed glioblastoma.
Authors: Elizabeth Robins Gerstner, Kyrre E. Emblem, Andrew S. Chi, April F. Eichler, Fred Hochberg, Jan Drappatz, Eudocia Carmen Quant, Andrew David Norden, Marco C Pinho, Pavlina Polaskova, Dominique Jennings, Marek Ancukiewicz, S. Percy Ivy, Patrick Y. Wen, Rakesh K. Jain, A. Gregory Sorensen, Tracy Batchelor
Journal: Journal of Clinical Oncology (2012)

2009 Background: Anti-angiogenic therapy is hypothesized to synergize with radiation and chemotherapy by improving tumor blood flow. We evaluated the tolerability, efficacy and potential mechanism of action of radiation, temozolomide, and cediranib in newly diagnosed glioblastoma patients. Methods: Newly diagnosed glioblastoma patients were treated with radiation, temozolomide, and cediranib followed by monthly temozolomide for 6 cycles and daily cediranib until tumor progression or toxicity as part of an IRB-approved, Phase Ib/II clinical trial. MRI scans including measurement of cerebral blood flow were performed at baseline, weekly during the 6 weeks of chemoradiation and then monthly. Radiographic response was determined by RANO criteria. Results: Six patients were enrolled in the phase Ib part of the study with cediranib 30 mg daily in combination with temozolomide and radiation. No dose-limiting toxicities were identified. Forty patients were enrolled in the phase II part of the study. Among the entire cohort of 46 patients, median age was 57 (range 35-74), median KPS was 90% (60-100), 36 patients underwent a subtotal resection and 10 underwent biopsy. 26/30 patients taking corticosteroids were able to taper corticosteroids during chemoradiation. Off study reasons included toxicity (14), disease progression (18), and patient preference (2). Five patients remain on study without disease progression and 20 patients have died. Median duration on study was 158 days. Median progression free survival was 288 days (95%CI 240,∞) and median overall survival was 786 days (95%CI 411 ,∞). Best radiographic response in patients who completed chemoradiation was CR in 2 patients, PR in 20 patients, and SD in 15 patients. Patients with increased tumor perfusion during chemoradiation survived nearly 1 year longer (mean OS=611 days) than patients with decreased perfusion (mean OS=269 days). Conclusions: Cediranib was well tolerated and led to improved PFS and OS compared to historical controls, particularly in those with improved perfusion. This combination is being evaluated in an ongoing randomized trial (RTOG 0837).
Real-world treatment with abiraterone acetate in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC).
Authors: Martin Boegemann, Martin Hatzinger, Dirko Hercher, Geoffrey Matus, Els Grieta Everaert, Catherine Dopchie, Denise Sheehan, Alison J. Birtle, Laura Garcia Alvarez, Lu Zou, Martin Kluska, Laurent Antoni, Geneviève Pissart, Martin Lukac, Lindsay Dearden
Journal: Journal of Clinical Oncology (2017)

239 Background: In the COU-AA-302 trial, abiraterone acetate plus prednisone (AAP) resulted in extension of radiographic progression-free survival (rPFS) and overall survival in chemotherapy-naïve mCRPC patients compared to prednisone alone. However, limited data on AAP treatment and outcomes is available in the real-world in this setting. The aim of this study is to describe the duration of AAP treatment in routine clinical practice in mCRPC patients prior to chemotherapy. Methods: The study was designed as a retrospective chart review of mCRPC patients identified through oncology and urology practice in Belgium, France, Germany and the UK. This first analysis reports baseline patient characteristics at AAP initiation for the first 224 patients. Treatment duration, PFS and rPFS were estimated using Kaplan-Meier curves. Potential factors associated with treatment duration were explored using the log-rank test. Results: Data from 224 mCRPC patients treated with AAP (Belgium: 67; Germany: 150; UK: 7; none from France) across 19 centres was considered in this initial analysis. At baseline, the median age was 75.5 years (interquartile range [IQR]: 69.0-82.0) and the median PSA level was 50.0 ng/mL (IQR: 21.0-121.0). Patients with visceral metastases (9.8%) and ECOG 2-3 (9.4%) were included in this study, in contrast to those included in the COU-AA-302 study. Median duration of AAP treatment was 11.6 months (95% confidence interval [CI]: 10.2-12.8), whilst median PFS and rPFS were 11.9 months (95% CI: 10.8-13.3) and 16.5 months (95% CI: 13.5-20.0), respectively. Reasons for discontinuing AAP involved PSA progression (52.2%), radiographic progression (38.9%), symptomatic progression (27.8%), non-toxic death (19.4%) and toxicity (2.2%). Treatment duration was significantly longer in mCRPC patients with either baseline ECOG status 0, lower PSA, alkaline phosphatase, aspartate aminotransferase, or lactate dehydrogenase levels (p &lt; 0.05). Conclusions: The results of this study suggest similar treatment duration and rPFS for mCRPC patients in this real-life cohort with poorer clinical features compared to those observed in the COU-AA-302 trial population.
Patterns of treatment outcomes in older patients with metastatic pancreatic cancer.
Authors: Hyun Ae Jung, Sung Hee Lim, Boram Han, Ho Young Kim, Hyo Jung Kim, Dae Young Zang, Joo Young Jung
Journal: Journal of Clinical Oncology (2017)

481 Background: Although pancreatic cancers are common in older age-groups, treatment approaches and outcomes are understudied in this population. We undertook this study to compare treatment outcomes for older patients with metastatic pancreatic cancer. Methods: Data from 167 patients aged 70 years or over with metastatic pancreatic cancer from January 2010 to July 2015, were analyzed. The clinic-pathologic variables and treatment outcome retrospectively reviewed. Results: One hundred and sixty three patients were identified. Among them, only 22.1% (n=36) patients receive palliative chemotherapy. The median age was 74.0 years old (range: 70-84) in the groups of chemotherapy as compared with 78.6 years old (range: 70-94.6) in the groups of supportive care. The median survival was 9.2 months (range: 1.0-24.9) in the chemotherapy group as compared with 2.3 month (range: 0.1-31.8) in the supportive care group. Among chemotherapy group, 50% (n=18) patients receive gemcitabine-based double therapy. Nine patients (30%) receive 2nd line chemotherapy. In group of supportive care, 55.8% (n=74) were survival less than 3 months. However, the median survival except for early deaths (less than 3 months) was 6.5 months. Conclusions: The current results showed that older patient with metastatic pancreatic cancer received chemotherapy less likely. However, the survival benefit from the chemotherapy was comparable outcome with historical data. Further study of identifying older patients who would benefit from cytotoxic chemotherapy was needed.