tbuckley/cabot-search huggingface dataset:
Etoposide and cytarabine as an effective and safe cytoreductive regimen for relapsed or refractory acute myeloid leukemia.
Authors: G. Nair, R. Karmali, S. A. Gregory, J. M. Shammo, H. C. Fung, A. Jimenez, P. Venugopal, M. L. Larson
Journal: Journal of Clinical Oncology (2011)

6539 Background: In relapsed/refractory AML, current second-line cytoreductive regimens remain relatively ineffective. A combination of mitoxantrone, etoposide and cytarabine (MEC) is commonly used as second-line therapy and confers response rates of 18-28% with a median OS of 25-32 weeks. The benefit of mitoxantrone here is unclear with cardiac toxicity limiting its use in the face of prior anthracycline exposure. In a retrospective study, we looked at the efficacy of a combination of etoposide and cytarabine (EC) as a cytoreductive regimen in this population. Methods: At our center, 32 patients with relapsed/refractory AML received etoposide 100mg/m2/day on days 1-5, and cytarabine 3 g/m2 twice daily on days 1-4, either as second- or third-line induction. Post induction bone marrow biopsies were used to determine response. Results: Of 32 patients, 15 were male. The median age was 55.5 years. Karyotypes were unfavorable in 20, intermediate in 9, favorable in 1, unknown in 2 patient(s). First line induction regimens included standard ‘7+3’ with cytarabine and idarubicin/daunorubicin (n=6), high-dose cytarabine with mitoxantrone (n= 25) or sapacitabine on trial (n=1). 20 patients were primary refractory; 12 had relapsed disease with median time to relapse of 8 months. 25 patients (78%) received EC as 2nd line and 7 (22%) as 3rd line therapy. 1 patient did not complete his EC course due to overwhelming infection. With EC, 15 patients (47%) achieved remission, 60% of whom received allogeneic stem cell transplant consolidation. 47% of patients in remission relapsed, all within 1 year. At a median follow-up of 14.7 months post EC, median OS was 4.5 months. In univariate analyses, males (p= 0.04) and patients ≥ 60 years of age (p=0.004) had a significantly worse PFS. Unfavorable cytogenetics did not affect PFS or OS. Complications with EC included hand-foot syndrome, neutropenic fever, infections and cytopenias. Conclusions: EC produces superior CRs and comparable OS when compared to MEC for relapsed/refractory AML without the use of a cardiotoxic drug. However, incorporation of novel agents such as clofarabine should be considered to further improve responses and survival.
A phase II trial of bryostatin in combination with cisplatin in patients with recurrent or persistent epithelial ovarian cancer: A California cancer consortium (CCC) trial
Authors: R. J. Morgan, J. H. Doroshow, P. Frankel, L. A. Leong, W. Chow, G. Fleming, A. A. Garcia, H. J. Lenz, D. Gandara
Journal: Journal of Clinical Oncology (2005)

5140 Background: The CCC has performed a Phase II pharmacokinetic trial of infusional bryostatin, a protein kinase C inhibitor isolated from the marine invertebrate bryozoan, Bugula Neritina, a member of the phylum Ectoprocta, in combination with cisplatin, in patients (pts) with recurrent platinum-sensitive or resistant ovarian cancer (OC) (E). Methods: Pts received bryostatin 45 mcg/m2 as a 72 hour continuous infusion followed by cisplatin 50 mg/m2. Cycles were repeated every three weeks. Dosages were chosen based on phase I data obtained by the CCC in a population of pts with mixed tumor types. Results: Eight pts with recurrent or persistent epithelial OC received 23 cycles of treatment. All pts had received previous platinum-based chemotherapy; two pts had received one prior course, five had received two prior courses, and one had received three prior courses of chemotherapy. The median age was 64 (range 32–72), and Karnofsky performance status 90 (range 80–100). A median of 3 cycles of chemotherapy were delivered (range: 1–5). The median progression-free and overall survivals were 3 and 8.2 months respectively. Best responses included two partial responses (one in a platinum-resistant pt), three pts with stable disease, and three progressions. All pts experienced Grade 3 or 4 toxicities including severe myalgias/pain/fatigue/asthenia in six pts, and severe nausea/vomiting/constipation in two other pts. One pt experienced a seizure and liver function tests were elevated in one other. Conclusions: A modest response rate is observed in pts with recurrent or persistent OC treated with the combination of bryostatin and cisplatin. The toxicity profile, however, observed in this pt population (primarily severe myalgias), precludes tolerability and prevents this combination from further investigation at this dose and schedule. It is possible that platinum pre-exposure in OC patients exacerbates observed toxicity. Phase II dosages of investigational agents in OC pts that are determined by phase I trials in pts with other tumor types should be chosen cautiously. (Supported by NCI Contract N01-CM-17101) No significant financial relationships to disclose.
Does absolute neutrophil count predict adverse tumor grade in African American men with prostate cancer?
Authors: N. Sadeghi, G. M. Badalato, G. W. Hruby, V. R. Grann, J. M. McKiernan
Journal: Journal of Clinical Oncology (2011)

4616 Background: African Americans (AA) are known to have a phenomenon called “benign ethnic neutropenia (BEN).” This is well described in both the hematology and oncology literature and has been implicated as a source of disparity in cancer outcomes among AAs. Since AA are more likely to have pathological subtypes of prostate cancer, this investigation sought to determine if absolute neutrophil count (ANC) and therefore BEN is associated with adverse pathologic findings following radical prostatectomy (RP) within a cohort of AA men. Methods: The IRB-approved Columbia University urologic oncology database was retrospectively reviewed for all patients undergoing a RP who met inclusion criteria: AA race, pre-operative CBC with differential, and known final RP pathology. Neutropenia was defined as ANC level ≤1.5x109/L (1.5). Clinical and pathological variables were characterized within the AA cohort and linear regression analysis was performed. The primary outcome was adverse tumor grade, defined as Gleason score 8-10. Results: From 1994 to 2010, a total of 331 patients were identified. In this cohort, 18 (5.5%) patients with an ANC ≤1.5 were identified; the mean age was 59.9 ± 7.5 years and mean follow-up time was 48.9 ± 43.1 months. There were 273 (82.48%) patients with pathological Gleason score 2-7 and 58 (17.52%) patients with Gleason score 8-10 (p=0.045). Between the neutropenic and non-neutropenic cohorts, there was no significant difference in age, race, preoperative PSA, gleason score, node status, or tumor margins (p>0.05). The two groups differed with respect to pathologic gleason score: a higher percentage of neutropenic patients had Gleason score ≥8 than non-neutropenic patients (38.9% vs 16.3%; p=0.045). Univariable regression analysis showed that ANC ≤1.5 was associated with adverse tumor grade (HR 1.25, CI 1.05-1.50; p=0.014). Multivariable regression analysis showed that ANC ≤1.5 was an independent predictor of adverse tumor grade (HR 1.24, CI 1.02-1.51; p=0.030). Conclusions: Neutropenia in AAs predicts adverse tumor grade at prostatectomy. Further studies are necessary to better understand the pathogenesis of prostate cancer, particularly as it relates to the African American population.
Prospective evaluation of atorvastatin in patients with PSA relapse after definitive treatment for prostate cancer
Authors: U. Nawaz, J. B. Charles, A. V. Hajdenberg, N. Cohen, J. Hajdenberg
Journal: Journal of Clinical Oncology (2008)

1526 Background: The chemopreventive effect of statins in prostate cancer is controversial. There have been no prospective trials. As a prospective evaluation would represent a formidable task, we decided to conduct an exploratory evaluation of the effects of atorvastatin on the PSA level in patients with noncastrate, hormone naïve, isolated PSA relapses (biochemical failure) after initial definitive therapy. All known agents with potentially chemopreventive effect have historically demonstrated measurable activity in patients with early stages of neoplasia. Methods: Prospective, phase II, 2 stage study conducted at M. D. Anderson Cancer Center Orlando. Alpha =.05, Beta=.2. Stage I sample size: 10. Alternate hypothesis to be rejected if responses (R) are less or equal 1. Stage II sample size: 29. Alternate hypothesis to be rejected if R less or = 5. P0=0.10, P1=0.30. Primary Endpoint: PSA response after 6 months of therapy (decline of 50% or more). Eligibility: patients with prostate adenocarcinoma with PSA progression after either definitive radiation therapy or radical prostatectomy. Patients with PSA doubling time <3 months were excluded. Intervention: Atorvastatin 20mg/day by mouth for 6 months. Results: Eight patients have been accrued in the study so far. Median age: 73 [53 to 79]. One patient withdrew from the study after 5 months. No patients had evidence of metastases at study entry. Baseline median PSA was 2.65ng/mL [1.2 to 19.1ng/mL]. Median PSA at the end of study was 3.4ng/mL [1.5 to 33.9]. Median time to progression: 4 months. Responses: 0/8 Progressions: 5/8 Minor progressions: 2/8 No change: 1/8. No serious adverse events were reported. Conclusions: Even though this exploratory trial is ongoing, it is highly probable the alternative hypothesis will be rejected during the first stage. We have not observed any meaningful effect of atorvastatin at its most commonly used dose on PSA levels in patients with early -hormone naïve- biochemical failure after 6 months of therapy. This preliminary data does not support the potential use of atorvastatin as a chemopreventive agent. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer
Patient understanding and impression of hematology/oncology fellows.
Authors: Brendan F. Curley, Quoc Van Truong, Anjaly Belur Curley, Mark Culp, Yanqing Hu, Mohammed Almubarak
Journal: Journal of Clinical Oncology (2012)

9 Background: Hematologists/oncologists spend years training in a fellowship program. At academic centers, patients receiving treatment are often seen by fellows. It has not been established what patients understand about fellowship training, therefore our purpose was to explore their understanding and if they are content with fellows taking part in their care. Methods: At West Virginia University/Mary Babb Randolph Cancer Center we drafted a survey. This anonymous and voluntary survey abstracted patient data that included: age, sex, race, level of education, type of cancer diagnosis, amount of time being treated for cancer, experience being cared for by fellows and basic knowledge of a hematology/oncology fellowship. Multiple-choice questions were drafted with 4 to 6 answer choices with no option for unknown. Surveys were collected over a three-week period from July 3, 2012 through July 24, 2012. Patients were surveyed at outpatient appointments, infusion center visits, and laboratory draws. Results: 226 surveys were collected. Statistical analysis was performed and a binomial regression was fit to the data. There is evidence that higher levels of education are more likely to give correct answers (p value 0.035). Patients who stated they had not seen a fellow or were unsure they had seen a fellow were more likely to select incorrect answers (p value 0.001). There is no statistical significance differentiating between cancer types in likelihood of getting answers correct (Table). 1.77% of those surveyed felt they completely understand the role of a fellow in their care, while 84.51% desired further information about fellows. Only 2.21% disliked having a fellow involved in their care. Conclusions: Patients at academic centers being seen by hematology/oncology fellows appear to have a lack of knowledge of a fellow’s role and background but have a desire to be educated. Educational initiatives can be introduced to teaching institutions to help patients better understand the role of a fellow. [Table: see text]
Efficacy of chemotherapy plus cetuximab according to metastatic site in <i>KRAS </i>wild-type metastatic colorectal cancer (mCRC): Analysis of CRYSTAL and OPUS studies.
Authors: C. Kohne, C. Bokemeyer, S. Heeger, U. Sartorius, P. Rougier, E. Van Cutsem
Journal: Journal of Clinical Oncology (2011)

3576 Background: In the CRYSTAL and OPUS studies, adding cetuximab to first-line chemotherapy (CT) improved clinical benefit in patients (pts) with KRAS wild-type (wt) mCRC. R0 resection of colorectal liver metastases is a potentially curative option in this setting. In a descriptive analysis of these trials the benefit of treatment according to metastatic site (liver-limited disease [LLD] and non-LLD) was investigated. Methods: Treatment arms were compared according to metastatic site for response rates (RR), R0 resection rates (R0R), progression-free (PFS) and overall survival (OS) times. Results: In CRYSTAL, R0 resection was significantly enhanced with CT + cetuximab vs CT alone (5.1 vs 2.0%, odds ratio 2.65, p=0.027). The proportion of pts with LLD was comparable in each study and treatment arm (21-30%). In both LLD and non-LLD pts, adding cetuximab to CT improved outcome across efficacy endpoints (Table). The highest R0Rs were seen in pts with LLD in the CT + cetuximab groups of both studies, with 2.3-fold (CRYSTAL) and 3.7-fold (OPUS) increases in rates vs CT alone. PFS was significantly higher in the CT + cetuximab arm in LLD pts in CRYSTAL (p=0.035) and in non-LLD pts in CRYSTAL (p=0.012) and OPUS (p=0.023). In non-LLD pts, adding cetuximab to CT significantly increased OS in CRYSTAL (p=0.013), prolonging median OS by 5.1 months, and prolonged OS by 3.4 months in OPUS. Conclusions: Adding cetuximab to first-line CT improved clinical outcome in mCRC pts with both LLD and non-LLD. In pts with non-LLD treated with FOLFIRI + cetuximab, the OS benefit exceeded 5 months. Efficacy according to treatment arm for patients with KRAS wt tumors grouped by metastatic site. All patients LLD Non-LLD CT CT + cetuximab CT CT + cetuximab CT CT + cetuximab CRYSTAL, n 350 316 72 68 278 248 RR, % 39.7 57.3 44.4 70.6 38.5 53.6 R0R, % 2.0 5.1 5.6 13.2 1.1 2.8 Median PFS 8.4 9.9 9.2 11.8 8.1 9.5 Median OS 20.0 23.5 27.7 27.8 17.4 22.5 OPUS, n 97 82 23 25 74 57 RR, % 34.0 57.3 39.1 76.0 32.4 49.1 R0R, % 3.1 7.3 4.3 16.0 2.7 3.5 Median* PFS 7.2 8.3 7.9 11.9 6.0 7.6 Median* OS 18.5 22.8 23.9 26.3 16.4 19.8 * Medians are in months.
Prospective evaluation of prescribing preferences (PPref) by U.S.-based oncologists in the postdocetaxel mCRPC patient.
Authors: Charles J. Ryan, Mark R. Green, Susan L. Britton, Arden Buettner, Maria Lankford, Douglas Neely
Journal: Journal of Clinical Oncology (2014)

258 Background: In May 2013 we studied the PPref of 90 U.S.-based medical oncologists (MOs) in the setting of various progression patterns during/after docetaxel-prednisone (DP) therapy for mCRPC using a validated, proprietary, live, case-based market research tool. A core case scenario with 4 DP therapy outcomes was constructed. Data were acquired using blinded audience response technology. Research support sources were double blinded. Methods: Core case - 59 y.o. with radical prostatectomy followed by PSA failure at 15 months (MOS) followed by salvage RT. 16 MOS post RT followed by rise in PSA and 3.5 cm pelvic node followed by over 42 MOS he responds to multiple systemic therapies (ST) including CAB, anti-androgen withdrawal, sipuleucel-T (Provenge) therapy, abiraterone-prednisone (AP). Now again has PSA progression, increasing bone disease and bone related symptoms followed by initiation of DPCT. PPref for 4 outcomes of DP were probed: (1.) 6 cycles (cy) of DP 75 mg/m2 Q 3 wk followed by pain elimination and PSA response followed by stop of DP due to cumulative myelosuppression and progressive fatigue. The pt. is more active off CT and he is PS1. 3 MOS later followed by asymptomatic 30% rise in PSA. (2.) 4 cy of DP followed by decrease in PSA, bone pain, and node size. Prior to cy 6, he has asymptomatic PSA progression. (3.) 4 cy of DP → decrease in PSA, node size, and bone pain. Prior to cy 6, he has PSA and pain progression. (4.) 2nd cy of DP followed by progression as best response, with increased bone pain, PSA, and pelvic nodal disease. Results: See Table. Conclusions: Second-line PPrefs following DPCT were scenario dependent. ENZ-based therapy is most common, even in this AP refractory patient population. Chemotherapy selection is more likely in the presence of more rapid and symptomatic disease progression. Despite the availability of active therapies, surveillance is still chosen by many in asymptomatic patients. [Table: see text]
Interaction between visfatin and resistin and the risk of colorectal adenoma.
Authors: Aiko Maejima, Yasuhide Yamada, Taiki Yamaji, Yoshitaka Honma, Natsuko T. Okita, Atsuo Takashima, Satoru Iwasa, Ken Kato, Tetsuya Hamaguchi, Yasuhiro Shimada, Shoichiro Tsugane
Journal: Journal of Clinical Oncology (2014)

438 Background: Colorectal adenoma is a well-established precursor lesion of colorectal cancer, so the prevention of adenoma may also contribute to the prevention of cancer. Adipocyte secretes hormones, namely adipocytokines, some of which are likely to be associated with malignancies such as colorectal, breast, and prostate gland cancer. Among several adipocytokines, resistin and visfatin have been suggested to be associated with the progression of colon cancer, and they could therefore be good biomarkers for colorectal adenoma and cancer. Methods: Prior to any procedures, healthy volunteers provided their venous blood, from which we obtained the plasma to measure concentrations of adiponectin, visfatin, and resistin. We underwent total colonoscopy, and identified 776 adenoma cases (522 males, 254 females), 734 controls (478 males, 256 females) were selected from those without adenoma. An unconditional logistic regression model was used to estimate odds ratios for colorectal adenoma after adjustment for potential confounders, including body mass index (BMI). Results: We found no positive association between the presence of colorectal adenoma and the levels of either visfatin (P trend: male 0.24, female 0.87), or resistin (P trend: male 0.85, female 0.71). After adjusting for potential confounders, we still saw no association. On the other hand, adiponectin levels showed a correlation with both BMI (P: male &lt;0.0001, female 0.0007) and the volume of fat. Furthermore, adiponectin levels indicated no positive correlation with visfatin (P: male 0.656, female 0.1445) or resistin (P: male 0.2116, female 0.1352). Conclusions: In this study, no association was observed between visfatin/resistin levels and colorectal adenoma, and they showed no positive correlation with BMI or the volume of intra-abdominal fat. However, other confounders may account for these results, so we plan to conduct further differential analyses.
The novel diagnostic method for colorectal cancer: Detection of methyl mercaptan from flatus.
Authors: Atsushi Ishibe, Mitsuyoshi Ota, Hiroshi Tsuboi, Akemi Takeshita, Yusuke Suwa, Shinsuke Suzuki, Hirokazu Suwa, Masashi Momiyama, Jun Watanabe, Takashi Kosaka, Kazuteru Watanabe, Hirotoshi Akiyama, Yasushi Ichikawa, Chikara Kunisaki, Itaru Endo
Journal: Journal of Clinical Oncology (2016)

529 Background: Fecal occult blood test screening for colorectal cancer (CRC) reduces cancer specific mortality through the detection of early stage disease. However, medical examination rate is very low in Japan because of the inconvenience of sampling of stool. On the other hand, it is reported that dogs can be trained to distinguish breath samples of patients with lung and breast cancer from those of control. It is unclear that odour materials become effective tools in CRC screening. The aims of this study were to evaluate the gas components in the flatus of CRC patients and to compare with healthy controls. Methods: Thirty-two patient before elective colorectal surgery in Yokohama City University and 13 healthy controls were enrolled in this study.The apparatus for gas sampling was placed in the toilet. Defecation gas from a patient in a toilet stool was collected in a 25L sampling bag. A fan (50 L / min ) was arranged to aspirate air in the toilet stool. Defecation gas components were collected as follows: (1) Air in the toilet stool was aspirated with the fan and passed through a commercial gas sensor. (2) Gas sampling started after the gas sensor detecting gas components.Volatile sulfur-containing compounds in sampling bag were injected into the gas chromatography by Entech pre-concentrator and analyzed. Results: The amount of methyl mercaptan was significant higher compared with control. Methyl mercaptan and hydrogen sulfide were related to tumor size (r = 0.415，p = 0.018, r = 0.454，p = 0.009). Methyl mercaptan tended to increase as the stage advances (p = 0.022）．Based on an optimal cut-off value calculated by ROC curve analysis had accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 68.9%, 68.8%, 69.2%, 84.6%and 47.3%, respectively, for the diagnosis of CRC. Conclusions: The methyl mercaptan from the toilet stool during defecation was increasing in CRC patients. Measurements of methyl mercaptan suggests possibility of more easily and precise colorectal cancer screening.
New primary palliative care (PC) model for community cancer clinics (CCC).
Authors: Cheruppolil R. Santhosh-Kumar, Deborah Gray, Stephanie Struve, Carol Huibregtse, Qiaofang Chen
Journal: Journal of Clinical Oncology (2016)

159 Background: Our CCC serving a mixed rural/urban population is part of a large integrated healthcare system in Eastern WI. The closest PC specialist/team is 45 miles away at one of the tertiary care facilities. To fill this service gap we implemented a primary PC model. An initial outpatient palliative care family conference (OFC) and use of cancer nurse navigators (CNN)are hallmarks of this program. Methods: The VLCC, housed in a standalone facility is staffed by two medical oncologists and one radiation oncologist and has an infusion center and a full-fledged radiation oncology unit with support staff, including cancer nurse navigators, research nurses, social workers, a clinical psychologist, a pharmacist, a nutritionist, a therapy dog and a chaplain. Specialized pain management teams and services like acupuncture and hypnotherapy are readily available in the community. The patients have had access to multiple clinical trials since 2004. A team of a physician champion, a CNN and a social worker prioritized the needs and designed a program with support from system leadership. A CNN took additional training in PC. Funding from a research grant provided support for an occupational therapist (OT). Difficulties in communication was identified early as a barrier to integration of PC. OFCs were designed and conducted to discuss multiple domains of palliative care and referrals were made to different services. Pre and post enrollment surveys were administered. The following flow diagram was used (see Table). Results: In 2015, of 334 new patient visits for all stages of cancer, 32 were managed through the new PC model. Patient satisfaction scores were near 100%. Detailed methodology and data analyses will be presented. Conclusions: A successful new model of early integration of PC that is easily replicable in communities without access to specialist PC services is presented. [Table: see text]