tbuckley/cabot-search huggingface dataset:
Association of renal cell carcinoma and hematologic malignancy.
Authors: Leticia Varella, Rangaswamy Chintapatla, Peter H. Wiernik, Valerie Rusciano, Janice P. Dutcher
Journal: Journal of Clinical Oncology (2013)

449 Background: An increased incidence of both RCC and HM occurring in the same patients has been reported. Also, a relationship between adenocarcinoma and HM has been previously suggested. Moreover, detailed family history in our patients with RCC suggested an increased incidence of HM in their family members. The purpose of this study is to characterize the HM in relatives of patients with RCC. Methods: Data from 700 patients with RCC seen by us from 2004 to the present were retrospectively evaluated through chart review. The patient, family history and pathology characteristics were collected to determine the frequency of HM in first and second-degree relatives of patients with RCC. Pedigrees were then constructed and subtypes of HM were characterized. Results: A family history of HM was observed in 74 relatives involving 59 families. Of these, 50/74 cases of HM were in first-degree relatives and 19/74 were in second-degree relatives. The most common HMs were lymphoma and leukemia: 24 non-Hodgkin’s lymphoma, 8 Hodgkin’s lymphoma, 8 lymphoma not further specified (NOS), 11 chronic lymphocytic leukemia, 1 chronic myeloid leukemia, 1 acute myeloid leukemia, 5 acute leukemia NOS and 4 leukemia NOS. Other HM observed were multiple myeloma in 2 patients, Waldenström’s macroglobulinemia, myelodysplastic syndrome, and myelofibrosis. Additionally, 2 relatives had blood cancers that were NOS. Of the 59 patients with RCC, 40 had clear cell histology, 4 papillary, 3 chromophobe, 1 sarcomatoid, 1 transitional and in 10, RCC histology was not recorded. Conclusions: HM is observed in patients with RCC with increased frequency compared with the SEER database. We now observed an increased frequency of HM in relatives of patients with RCC. The majority of HMs observed were B-cell malignancies, as we previously reported for HMs that occur in patients with breast cancer or RCC. The etiology of this association remains unclear, but suggests a common etiopathogenesis for RCC and B-cell tumors. Genetic mutations, hereditary immunological defects, and environmental factors may be involved. A larger study with statistical evaluation for confirmation is required. We plan to collect serum and tissue samples from patients and relatives for future molecular studies.
Analysis of dermatologist density and melanoma mortality.
Authors: S. Aneja, S. Aneja, J. S. Bordeaux
Journal: Journal of Clinical Oncology (2011)

6042 Background: Previous reports have drawn associations between physician workforce and cancer outcomes. We sought to determine the association between dermatologist density and melanoma mortality in US counties. Methods: A regression model was developed to demonstrate the association between melanoma mortality and dermatologist density. We also examined the effect of age, race, education, income, unemployment rate, health insurance rate, density of primary care physicians, melanoma incidence, county demographics (metropolitan vs. non metropolitan), access to hospitals with oncologic services and health professional shortage area classification on melanoma mortality. Data were collected from the Area Resource File, US Centers for Disease Control, and National Cancer Institute’s Surveillance, Epidemiology, and End Results program and National Program for Cancer Registries. Results: Multivariate analysis demonstrated that the presence of >0 to 1 dermatologist per 100,000 people was associated with a 35% reduction in melanoma mortality (95% CI 13.4% to 56.6%) when compared to counties with no dermatologist. The presence of >1 to 2 dermatologists per 100,000 people was associated with a 53% reduction in melanoma mortality (95% CI 30.6% to 75.4%). Having more than 2 dermatologists per 100,000 people did not further decrease melanoma mortality. Melanoma mortality was also decreased in metropolitan counties (30.3%, 95% CI 17.3% to 43.3%) and in counties where there are hospitals with oncology departments (1.9%, 95% CI 0.6% to 3.1%). Melanoma mortality rates were increased in counties with higher incidence of melanoma (2.3%, 95% CI 1.6% to 3.1%), greater Caucasian population (1.5%, 95% CI 1.1% to 1.9%), and greater health insured populations (1.5%, 95% CI 0.2% to 2.8%). Age, education, income, primary care provider density, health professional shortage area classification, and unemployment rate were not associated with melanoma mortality. Conclusions: We found that a greater dermatologist density is associated with a reduction in melanoma mortality when compared to counties that lacked a dermatologist.
Patients with metastatic renal cell carcinoma (mRCC) receiving sunitinib in “real-world” clinical practice: Baseline characteristics and treatment efficacy
Authors: J. M. Clement, D. F. McDermott, T. K. Choueiri, A. J. Brick, C. Kwabi, K. Shah, J. R. Weiner, M. S. Duh, M. P. Neary, W. K. Oh
Journal: Journal of Clinical Oncology (2008)

16071 Background: Sunitinib and other antiangiogenesis inhibitors have emerged from clinical trials as promising therapies for mRCC. However, patients in “real-world” clinical practice may differ from those in trials, potentially leading to differences in efficacy. The goal of this study is to describe baseline characteristics and treatment efficacy among patients receiving sunitinib outside of clinical trials. Methods: A retrospective review of medical records was performed in 2 large tertiary oncology centers. Patients were included in the study if they were ≥ 18 years of age, had a histological diagnosis of mRCC, and received ≥ 1 prescription for sunitinib. Trial patients were excluded. Descriptive analyses were conducted to characterize patients by various demographic and clinical factors as of sunitinib initiation. Objective response rate (ORR) was assessed based on RECIST criteria (confirmed or unconfirmed by a 2nd assessment). Patient observation was truncated at 15 months to mimic published phase 3 trial results. Results: Preliminary results are presented below. The median duration of sunitinib treatment was 5.4 months (range 2.0–15.0). Brain metastasis, ECOG ≥ 2, and prior cytokines, all exclusion criteria in the phase 3 trial, were observed in the clinical practice and were associated with a lower ORR. The overall ORR (23.1%, 95% CI=9.9–36.3%) is 25% less than the 31% ORR reported in the phase 3 trial. (Motzer, N Engl J Med, 2007) ORR varied considerably across factors, suggesting that some subgroups may not respond well to sunitinib. Data collection is ongoing; updated results will be presented. Conclusions: Patients receiving sunitinib for mRCC outside of trials may have a different risk factor profile and lower ORR than trial patients, suggesting that clinical trial results may not be generalizable. No of patients (%) ORR % All patients 39 23.1 Age, yrs 30-59 21 (53.9) 28.6 60-89 18 (46.2) 16.7 Gender Female 11 (28.2) 36.4 Male 28 (71.8) 17.9 Number of metastatic sites 1 11 (28.2) 27.3 2 13 (33.3) 23.1 ≥ 3 15 (38.5) 20.0 Bone Yes 11 (28.2) 18.2 No 28 (71.8) 25.0 Brain Yes 8 (20.5) 12.5 No 31 (79.5) 25.8 Liver Yes 4 (10.3) 50.0 No 35 (89.7) 20.0 Lung Yes 24 (61.5) 16.7 No 15 (38.5) 33.3 Lymph nodes Yes 18 (46.2) 22.2 No 21 (53.9) 23.8 ECOG performance status 0 17 (43.6) 35.3 1 12 (30.8) 16.7 2 3 (7.7) 0.0 Not available 7 (18.0) 14.3 Prior nephrectomy Yes 35 (89.7) 22.9 No 4 (10.3) 25.0 Prior cytokine therapy Yes 7 (18.0) 14.3 No 32 (82.1) 25.0 Prior radiation therapy Yes 7 (18.0) 14.3 No 32 (82.1) 25.0 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline Genentech, Novartis, Onyx/Bayer, Pfizer GlaxoSmithKline Pfizer Genentech, GlaxoSmithKline, Novartis, Onyx/Bayer, Pfizer, Wyeth
Prophylactic use of Granulocyte-colony stimulating factors (G-CSF) in cancer patients: Adherence to NCCN guidelines.
Authors: Rashi Khanna, Vyshak Alva Venur, Shraddha Narechania, Paul Elson, Hamed Daw, Timothy Peter Spiro, Abdo Haddad
Journal: Journal of Clinical Oncology (2016)

209 Background: G-CSF are used for prophylactic and therapeutic treatment of febrile neutropenia (FN). NCCN guidelines (version 1.2015) recommend prophylactic use of G-CSF based on the chemotherapy regimen and patient related risk factors, especially for the high (&gt; 20%) and intermediate (10-20%) risk groups for developing FN. This study investigates the practice patterns and adherence to NCCN guidelines for use of G-CSF at a community based academic outpatient facility. Methods: Cleveland Clinic IRB was obtained. Charts of all patients with underlying non-small cell lung cancer, small cell lung cancer, and breast cancer, treated in the year 2013, were reviewed for G-CSF use on their initial chemotherapy encounter. Risk assessment for developing FN was assessed based on individual risk factors and chemotherapy regimen. Analysis was obtained for appropriate guideline based use of G-CSF. Results: A total of 172 (n = 172) patients were included in the study. Overall, 63% (108/172) of patients had breast cancer; 81% (140/172) were female, most patients (64%, 108/170) were aged &lt; 65 years; 29% (49/172) had metastatic disease; and almost all patients (91%, 106/117) had good ECOG performance status (0 or 1). The overall risk of FN was estimated to be low (&lt; 10%) for 9% (16/172) of patients, intermediate (10-20%) for 45% (77/172) of patients, and high (&gt; 20%) for 45%. Overall, 5% (8/172) of patients did not follow the NCCN guidelines. Only 86% of the patients in metastatic group were adherent to NCCN guidelines compared to 99% of patients in non-metastatic group (p&lt; .01). Among patients with metastatic disease, 14% (7/49) did not follow NCCN guidelines; in a univariable analysis, among patients with metastatic disease - risk of neutropenia (p &lt; .0001), age (p &lt; .01), and prior chemotherapy and or radiation (p = .04), were associated with whether or not the NCCN guidelines were followed. Conclusions: In our limited study population, more use of G-CSF was seen among patients with metastatic cancer with a higher number of metastatic patients being non-adherent to NCCN guidelines. Further research is required to elucidate the potential benefit and cost-effectiveness of G-CSF use in the palliative setting.
Extended safety and efficacy data on triple combination therapy using S-1, cisplatin, and paclitaxel in patients with advanced gastric cancer in a multicenter phase II study.
Authors: H. Iwase, K. Ina, H. Goto, J. Haruta, T. Kumada, M. Shinoda, M. Sugihara, T. Tsuzuki, M. Shimada
Journal: Journal of Clinical Oncology (2010)

4074
Second-line chemotherapy with paclitaxel for elderly patients with advanced gastric cancer.
Authors: Akihiro Ohba, Atsuo Takashima, Takamasa Nishiuchi, Yoshitaka Honma, Satoru Iwasa, Natsuko Okita, Ken Kato, Tetsuya Hamaguchi, Kengo Nagashima, Narikazu Boku
Journal: Journal of Clinical Oncology (2016)

108 Background: Survival benefits of second-line chemotherapy such as weekly paclitaxel (wPTX) for patients with advanced gastric cancer (AGC) were shown in several phase 3 trials. However, these trials included a small proportion of elderly patients, and few elderly patients receive second-line therapy in clinical practice. The aim of this study was to compare the efficacy and safety of second-line chemotherapy with wPTX between elderly and non-elderly patients. Methods: The subjects of this retrospective study were AGC patients who received wPTX as second-line chemotherapy between January 2002 and August 2014, fulfilling the following selection criteria; 1) pathologically proven metastatic or recurrent gastric adenocarcinoma, 2) receipt of wPTX after platinum or fluoropyrimidine containing chemotherapy. Patients were divided into two groups by age: ≥ 75 years old (elderly group) and &lt; 75 years old (non-elderly group). Response rate (RR) in patients with measurable lesions, overall survival (OS), progression-free survival (PFS), post-progression survival (PPS) and adverse events were evaluated. Hazard ratios of survival were adjusted by prognostic factors using Cox proportional hazard model. Results: A total of 272 patients, 31 elderly and 241 non-elderly, were selected in this study. RRs were 6.2% (1/16) in the elderly group and 12.7% (15/118) in the non-elderly group (p = 0.69). While PFS was similar between two groups (median 2.4 vs. 3.6 months, adjusted hazard ratio [HR] 1.18, p = 0.46), the elderly group showed shorter OS than the non-elderly group (median 5.1 vs. 6.1 months, adjusted HR 1.49, p = 0.06), associated with relatively shorter PPS (median 2.2 vs. 2.6 months, adjusted HR 1.40, p = 0.11). There were no remarkable differences in the incidences of grade 3 or higher adverse events between the two groups (hematologic 38.7 vs. 41.1%; non-hematologic 25.8 vs. 23.7%). No treatment related deaths were observed in either group. Third-line chemotherapy was administered in 19.4% of elderly group and 35.3% of non-elderly group (p = 0.11). Conclusions: It is suggested that second-line chemotherapy with wPTX for AGC may be tolerable and have some clinical benefits for elderly patients as well as for non-elderly patients.
Atherothrombotic Risk Stratification and Ezetimibe for Secondary Prevention
Authors: Erin A. Bohula, David A. Morrow, Robert P. Giugliano, Michael A. Blazing, Ping He, Jeong-Gun Park, Sabina A. Murphy, Jennifer A. White, Y. Antero Kesaniemi, Terje R. Pedersen, Adrian J. Brady, Yale Mitchel, Christopher P. Cannon, Eugene Braunwald
Journal: Journal of the American College of Cardiology (2017)
Statin use at the time of initiation of androgen deprivation therapy (ADT) and time to progression (TTP) in patients with hormone-sensitive prostate cancer.
Authors: Lauren Christine Harshman, Mari Nakabayashi, Wanling Xie, Xiaodong Wang, Loana Valenca, Lillian Werner, Lorelei A. Mucci, Gwo-Shu Mary Lee, Christopher Sweeney, Mark Pomerantz, Philip W. Kantoff
Journal: Journal of Clinical Oncology (2015)

148 Background: Statin use has been associated with a decreased risk of recurrence after local therapy and a lower risk of prostate cancer mortality. There is little known about the association between statin use and prostate cancer progression among men newly initiating ADT. We undertook an analysis of the association between statin use at the time of ADT initiation and TTP. Methods: We queried our institutional clinical database (Prostate CRIS), which captures clinicodemographic data, treatment details, and clinical outcomes of our prostate cancer patients (pts), to identify pts treated with ADT for biochemical recurrence or metastatic disease. Date of progression and statin use at ADT initiation were collected by medical record review. Progression was defined as 3 PSA rises. Date of progression was defined as date of first rise (nadir + &gt;0.02 ng/ml). The association between statin use and TTP on ADT was estimated from multivariable Cox regression, adjusting for known prognostic factors: biopsy Gleason score, primary therapy type, metastatic status, and PSA at ADT initiation. Results: Of the 926 patients eligible for analysis, 283 (31%) were taking a statin at ADT initiation. Statin users were less likely to have M1 (11 vs. 18%) or N1 (5 vs 10%) disease at diagnosis and more likely to have received local therapy +/-ADT compared to nonusers. They were also less likely to have metastases at ADT initiation (53 vs 63%). Median PSA at diagnosis and at ADT initiation were lower among statin users. Duration from diagnosis to ADT initiation was longer in users. After a median follow-up of 5.8 years, 644 pts (70%) had progressed on ADT and median TTP on ADT was 20.3 months (95% CI: 18,24). Men on statins had a longer median TTP on ADT compared to nonusers (27.5 vs 17.4 months). The association remained statistically significant after adjusting for known prognostic factors [adjusted HR=0.83 (p=.039)]. Conclusions: In our cohort, statin use at the time of ADT initiation was associated with a significant increase in TTP on ADT even after adjusting for established prognostic factors. Further investigation into the mechanisms behind this observation is planned.
Survival results of a randomized, phase III trial of nab-paclitaxel and carboplatin compared with cremophor-based paclitaxel and carboplatin as first-line therapy in advanced non-small cell lung cancer.
Authors: M. A. Socinski, I. N. Bondarenko, N. A. Karaseva, A. Makhson, I. Vynnychenko, I. Okamoto, J. K. Hon, V. Hirsh, P. Bhar, G. I. Berk, J. L. Iglesias
Journal: Journal of Clinical Oncology (2011)

7551 Background: The nanoparticle albumin-bound formulation of paclitaxel, nab-paclitaxel, reaches the tumor microenvironment more efficiently than conventional formulations via caveolae-mediated transcytosis, and is preferentially taken up by cancer cells. In clinical and preclinical studies, nab-paclitaxel was efficacious and safe in metastatic breast cancer and in various other solid tumor types, including non-small cell lung cancer (NSCLC). This phase III trial compared the efficacy and safety of nab-paclitaxel plus carboplatin (nab-PC) vs paclitaxel plus carboplatin (PC) in advanced NSCLC. Methods: First-line stage IIIB or IV NSCLC patients (ECOG 0/1) were randomized to receive carboplatin AUC6 q3w and either nab-paclitaxel 100 mg/m2 qw w/o premedication (n = 521) or paclitaxel 200 mg/m2 q3w with premedication (n = 531). Primary endpoint was overall response rate (ORR) by independent radiologic review. The main secondary endpoints included progression-free survival (PFS), overall survival, and safety. Results: Baseline and histologic characteristics were well balanced between arms. nab-PC produced higher ORR compared with PC (33 vs 25%, P = 0.005). Age (≥75 vs <75 years old), smoking status, and geographic location did not effect primary efficacy outcome. Particularly, ORR was 34 vs 26% in Russia/Ukraine, 35 vs 27% in Asia/Pacific, and 25 vs 20% in North America/Australia, respectively. nab-PC was well tolerated, with significantly improved safety profile vs PC despite 30% higher mean total paclitaxel dose delivered (1514 vs 1169 mg/m2). Of the statistically significant grade ≥3 adverse events, neutropenia, neuropathy, myalgia, and arthralgia were lower in the nab-PC arm, and thrombocytopenia and anemia were lower in the PC arm. Interim PFS analysis with 47% events revealed no significant differences between the 2 arms. Final survival data with ≥70% patients with an event will be presented at ASCO. Conclusions: The primary endpoint was met, with significantly improved ORR. Interim PFS did not show a difference between the arms. nab-PC is efficacious and safe as first-line therapy for advanced NSCLC.
The effect of guidelines, policy initiatives, and feedback tools on hospital adherence with the 12-node measure for colon cancer.
Authors: Jennifer L. Paruch, Ryan P. Merkow, Mila H. Ju, David Porter Winchester, Clifford Y. Ko, Karl Y. Bilimoria
Journal: Journal of Clinical Oncology (2013)

65 Background: Examination of &gt; = 12 lymph nodes after colectomy is one of few surgical process measures. Several initiatives have targeted this measure; one tool developed by the Commission on Cancer (CoC) provides benchmarked feedback on hospital performance (CP3R). Our objectives were to (1) examine changes in measure performance over time in response to guidelines, policy initiatives, and feedback, and (2) identify hospital characteristics associated with failure to improve adherence. Methods: Patients having surgery for Stage I-III colon cancer (1990-2010) were identified from the National Cancer Data Base (NCDB). For hospital-level analyses, NCDB and American Hospital Association (2010) data were merged. Hospital CP3R use was obtained from the user log system. Multivariable logistic regression adjusted for age and tumor factors was used to identify hospital characteristics associated with adherence in 2009-2010 (&gt; = 12 nodes in &gt; 80% of patients). Results: The percentage of patients with &gt; = 12 nodes removed increased from 31.5% in 1990 to 84.1% in 2010 (p &lt; 0.0001). The percentage of adherent hospitals increased from 2.2% in 1990 to 70% in 2010 (p &lt; 0.0001). The steepest increase in adherence occurred with introduction of CP3R. Median CP3R use increased from 5 to 57 logins annually (2005-2010). Hospital predictors of poor adherence included low volume, community hospital type, private ownership, rural location, and lower number of specialists (Table). Conclusions: Guidelines, policy initiatives, and feedback tools have helped dramatically increase adherence with the 12-node measure, but small, non-academic hospitals have been slower to improve. Additional efforts are needed to understand barriers and improve adherence at these facilities. [Table: see text]
Correlative biomarkers in a phase II study of dasatinib (D) and weekly (w) paclitaxel (P) for patients (Pts) with metastatic breast carcinoma (MBC).
Authors: P. G. Morris, J. C. Chang, A. Abbruzzi, S. Patil, S. Modi, A. D. Seidman, N. T. Sklarin, L. Norton, C. Hudis, M. N. Fornier
Journal: Journal of Clinical Oncology (2010)

TPS124 Background: Src kinase plays an important role in BC cell survival within bone marrow. Src activation is associated with late-onset bone metastases (Zhang, Cancer Cell 09). In ER-negative BC, differential expression of various tyrosine kinases (TK), including KIT and ABL has been suggested. Therefore inhibition of TKs, including Src, represents a novel therapeutic approach. D is a potent inhibitor of 5 oncogenic TKs; BCR-ABL, SRC family, c-KIT, PDGFRβ and many EPH kinases (Shah, Science 04), with activity in CML and GIST. D inhibits VEGF-stimulated proliferation, has potent bone anti-resorptive activity and selectively inhibits basal-type BC growth. Preclinically, the combination of P + D showed greater antitumor activity than either single agent. In an ongoing phase II study we are investigating several biomarkers of response. Methods: Pts with measurable, HER2-negative MBC, and treated with ≤2 prior rx for metastatic disease, regardless of ER status, are eligible. Pts must have adequate renal, hepatic and bone marrow function + unstained slides from prior surgery. Given clinical concerns of edema from D pts with pleural/pericardial effusions are excluded. IV bisphosphonates are withheld < 8 wks due to risk of decreased calcium. Pts must not be taking concomitant Category I drugs associated with risk of Torsades de Pointes, known inhibitors of CYP3A4 (by which D is metabolized) or H2 blockers/proton pump inhibitors (which affect bioavailability). Pts receive wP 80 mg/m2 IV 3/4 wks and D 120 mg orally daily. 23 pts will be enrolled; if ≤ 3 responses are observed (null hypothesis 15% RR), the study will be terminated early, if ≥4 responses are seen, enrollment will be extended to 55 pts. If > 12 responses are seen wP+D will be considered worthy of further testing. Secondary efficacy endpoints include clinical benefit rate (CR+PR+SD > 6 mths), TTP, PFS and duration of response. The investigation of putative biomarkers of response will include: 1. Tumor mRNA expression of EphA2, IGFBP2, Caveolin, Phospho-caveolin and SFK substrates. 2. Plasma assays of p-SRC, VEGFR2, Collagen Type IV and Circulating Tumor Cells at baseline and at 8 wks. These biomarkers will be correlated with efficacy. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb