tbuckley/cabot-search huggingface dataset:
Clinical outcomes and predictive value of chromogranin A (CgA) and pancreastatin (PcSt) in liver-directed therapies (LDTs) for well-differentiated metastatic neuroendocrine tumors.
Authors: Eric Steven Engelman, Roberto Leon-Ferre, Boris G. Naraev, Nancy Sharma, Anna M Button, Gideon Zamba, Shiliang Sun, Thomas M. O'Dorisio, Thorvardur Ragnar Halfdanarson
Journal: Journal of Clinical Oncology (2012)

e14620 Background: LDTs have been shown to improve time to tumor progression and morbidity in metastatic neuroendocrine tumors (mNETs). CgA and PcSt are being used to predict and evaluate response to LDTs. Methods: Medical records of 42 mNET patients (pts) with hepatic metastases treated with either bland hepatic artery embolization (HAE), chemoembolization (HACE), or hepatic radioembolization (HRE) at the University of Iowa from 2001 to 2011 were analyzed. Time to progression (TTP) and overall survival (OS) were calculated using Kaplan-Meier analysis. PcSt and CgA were compared using a standardized mean Results: The tumors were located in the small bowel in 21 pts (50%), pancreas in 8 (19%), lung in 2 (5%), and other locations in 11 pts (26%). 13 pts had HAE, 17 had HACE and 12 had HRE. 20 pts had a second procedure with 6 receiving HRE, 9 HAE and 5 HACE. There was no significant difference in initial radiographic response among the three treatments (p = 0.082). TTP was similar between HRE (15.1 months) and HAE or HACE (HA(C)E) (19.6 months) (p= 0.968). There was a trend towards an increased TTP in pts receiving HACE (33.4 months), compared to HAE (12.1 months) or HRE (15.1 months) (p = 0.512). The overall survival for all pts from the first intervention was 41.9 months. There was no significant difference in symptom improvement among the treatment groups (p = 0.265). HRE and HA(C)E had no difference in post-therapy fever (p=0.236), vomiting (p=0.470), or abdominal pain (p=0.139). There was no difference between HA(C)E and HRE in pre-therapy CgA (p= 0.1913) or PcSt (p=0.983) nor was there a difference in post-therapy change of CgA (p=0.233) and PcSt (p=0.158). TTP did not correlate with the pre-therapy CgA (p=0.131) or PcSt (p=0.630) nor the change in the post-therapy CgA (p=0.299) or PcSt (p=0.208). Conclusions: There was no significant difference in TTP in patients treated with HRE compared to patients treated with HAE or HACE in this cohort. No single therapy was better than another in reducing symptoms. Baseline CgA and PcSt and post-therapy marker changes did not predict TTP and there was no difference in post-therapy marker changes based on treatment type.
Phase II study of amrubicin (AMR) and carboplatin (CBDCA) for invasive thymoma (IT) and thymic carcinoma (TC): NJLCG0803.
Authors: Yosuke Kawashima, Akira Inoue, Shunichi Sugawara, Masao Harada, Kunihiko Kobayashi, Toshiyuki Kozuki, Shoichi Kuyama, Tomohiro Sakakibara, Makoto Maemondo, Hajime Asahina, Akiko Hisamoto, Taku Nakagawa, Toshihiro Nukiwa
Journal: Journal of Clinical Oncology (2013)

7530 Background: There has been no standard chemotherapy for advanced thymic malignancies including IT and TC although anthracycline or platinum agents have been commonly used for them. AMR, a new anthracycline agent, was approved for lung cancer in Japan and we had previously conducted some prospective studies of AMR combined with CBDCA for patients with small-cell lung cancer, which revealed this regimen was active with acceptable toxicity. The objective of this study is to evaluate the efficacy and safety of this combination for patients with advanced thymic malignancies. Methods: Patients with histologically confirmed thymic malignancies received AMR (35 mg/m2, day1-3) and CBDCA (AUC 4.0, day1) every 3 weeks. Patients who underwent previous chemotherapy received reduced dose of AMR (30 mg/m2). The primary endpoint was overall response rate (ORR), and secondary endpoints were progression-free survival (PFS), overall survival and toxicity profile. Assuming that ORR of 75% and 45% would indicate the potential usefulness while ORR of 50% and 20% would be the lower limit of interest, with alpha = 0.10 and beta = 0.20, for IT patients and TC patients, respectively, 18 IT patients and 16 TC patients were at least required. Results: From December 2008 to October 2012, 51 patients (18 IT and 33 TC) were enrolled from 20 institutions in Japan. Patients’ characteristics are as follows; male/female 35/16; median age 66 (range 39-78); performance status 0/1 24/27. The ORR and disease control rate were 17% and 89% in IT, and 30% and 85% in TC. Preliminary median PFS was 7.6 months in both groups. Toxicity was generally moderate and no treatment related death was observed. Conclusions: This is the largest prospective study of chemotherapy for advanced thymic malignancies. AMR combined with CBDCA was effective for TC patients with acceptable toxicities. Clinical trial information: R000001598.
Association of stromal cell gene expression with response to neoadjuvant chemotherapy in locally advanced breast cancer.
Authors: Rene Aloisio da Costa Vieira, Angelo Gustavo Zucca Matthes, Maria Lucia Hirata Katayama, Victor Piana Andrade, Rosimeire Aparecida Roela, Luiz Guilherme C.A Lima, Simone Maistro, Maria Mitzi Brentani, Maria A. A. Koike Folgueira
Journal: Journal of Clinical Oncology (2014)

11129 Background: There is increasing evidence that breast cancer behavior is a reflection of an interactive signaling between the malignant epithelial compartment and the surrounding microenvironment. A high stromal gene expression, characterizing a reactive stroma, was associated with resistance to neoadjuvant chemotherapy, in indirect analysis. Our aim was to detect a stromal cell signature associated with response to neoadjuvant chemotherapy in locally advanced breast cancer, using a direct approach, consisting of stromal cell selection, through laser microdissection. Methods: Twenty one patients treated at Hospital de Câncer de Barretos were included. Patients were diagnosed with invasive ductal carcinoma, except one (lobular invasive carcinoma); median age was 44.5 years; all presented stage III disease; mean tumor dimension was 6.89 cm. Eleven tumors were luminal HER2 negative; 5 HER2 positive [3 ER(+); 2 ER(-)] and 5 triple negative. All patients were submitted to neoadjuvant chemotherapy (4AC fol...
Development of a new equation to estimate GFR in cancer patients.
Authors: Michael Patvin Chu, Larissa McCaw, Cynthia Stretch, John Hanson, Michelle Kuzma, Vijaya L. Damaraju, Vickie E. Baracos, Michael B. Sawyer
Journal: Journal of Clinical Oncology (2013)

e13503 Background: Renal function affects chemotherapy pharmacokinetics. Carboplatin dosing by Calvert’s formula is more pharmacologically rational, but requires an accurate glomerular filtration rate (GFR). Calvert argues that this requires measuring GFR (mGFR) instead of an estimated GFR (eGFR). Considering skeletal muscle is the major source for creatinine, this study looks to develop a new eGFR equation in cancer patients using lean body mass (LBM). Methods: We prospectively followed 22 stage IV cancer patients (10 female, 12 male; median age 69) who received carboplatin. mGFR by 24 hr creatinine clearance was compared to eGFR by Wright, Cockcroft-Gault (CG), CKD-EPI, MDRD and CT-determined LBM (eGFR = [Muscle Surface Area X 42]/CR). Simulated carboplatin dosing with each eGFR was then compared retrospectively in 100 Non-Small Cell Lung Cancer (NSCLC) patients for accuracy. Results: MDRD, CG, and Wright equations correlated variably with mGFR (R 2 0.47, 0.57, and 0.69 respectively). Conversely, mGFR strongly correlated with LBM eGFR (R 2 0.84). The Table compares eGFR calculations with mean residual error. In simulated carboplatin dosing of 100 stage IV NSCLC patients using LBM and CG eGFR, the mean residual error of the CG-determined carboplatin dose was 10% (0.5% min, max 39.7%, median 9.3%), assuming the LBM eGFR was better at estimating eGFR. This means that in approximately half of patients, carboplatin dose may be incorrect by CG if the new LBM eGFR method is truly more accurate. Conclusions: We propose a new formula for eGFR in cancer patients that appears superior to current formulas and may have implications for chemotherapy efficacy and toxicity. Studies to validate this formula are under way. [Table: see text]
Abstract P089: Early CVD Events by Race and Sex: Does Risk for Atherothrombotic- and Hypertension-related Events Differ by Race and Sex? The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Cora E Lewis, Catarina I Kiefe, David R Jacobs, David C Goff, James M Shikany, Stephen Sidney, Daniel Duprez, Donald Lloyd-Jones, Jared Reis, Pamela J Schreiner, Raegan Durant, Young-il Kim, Kiarri Kershaw
Journal: Circulation (2017)

African Americans (AA), both men (M) and women (W), have higher CVD mortality rates than European Americans (E), but AAM have lower prevalence of coronary calcified plaque than WM. AAs also have higher blood pressure (BP) and HDL-C than W; HDL-C is lower in M than W. We tested the hypotheses that AA race is related to higher risk of hypertension (HTN)-related events, and being male is related to higher risk of atherothrombotic (ATH)-related events, placing AAM at particularly high risk for CVD. Methods: We used baseline risk factor data, and adjudicated events through 28 years of follow-up from the CARDIA study which recruited 5,115 participants aged 18-30 years at baseline (1985-6). ATH-related events included acute coronary syndrome with or without MI, coronary revascularization, and CHD and other atherosclerosis death. HTN-related events included heart failure, end-stage renal disease (ESRD), stroke, and death due to cardiomyopathy. CVD events excluded ESRD and included peripheral artery disease procedures. We analyzed time to first event censoring at death without incident CVD and at follow-up end. We built adjusted Cox models with forward selection including race, sex, age, education, and smoking status as forced predictors and selecting among physical activity, anthropometry, glycemia, lipid, and blood pressure risk factors. Results: In unadjusted analyses, risk of HTN-related events was related to race (p&lt;0.01) but not sex (p=0.35), ATH-related events to sex (P&lt;0.01) but not race (p=0.44), and CVD events to race (p&lt;0.01) and sex (P&lt;0.01). Unadjusted, all risk factors were associated with both HTN- and ATH-related events, except physical activity was not related to ATH and CVD events. After adjustment (table), AAM had higher risk of HTN- and ATH-related events, EM had higher risk of ATH-related events, AAW had higher risk of HTN-related events, and all had higher risk of CVD events than EW. Conclusion: Race and sex are differentially associated with early HTN- vs ATH-related events, and AAM were at increased risk for both.
Medical Oncologists’ and Surgeons’ approaches to communication of breast cancer recurrence risk.
Authors: Aaron Sabolch, Brian Zikmund-Fisher, Nancy K. Janz, Sarah T. Hawley, Kent A. Griffith, Reshma Jagsi
Journal: Journal of Clinical Oncology (2015)

6543 Background: Risk of breast cancer recurrence can be estimated with tools such as Adjuvant! Online, but little is known about how medical oncologists and surgeons use such tools or communicate risk information to patients. Methods: In 2012, we surveyed 750 medical oncologists and 750 surgeons identified using the AMA Physician Masterfile (a comprehensive physician list not limited to AMA members). Using a vignette, we evaluated risk communication practices (discussing risk using descriptive words, discussing risk using numbers, using online calculators, providing copy of risk estimates) and analyzed correlates of specific approaches in a logistic regression model that included physician (e.g., gender, specialty) and practice characteristics (number of breast cancer patients seen in past year, multidisciplinarity [i..e., offering same-day multi-specialty appointments]). Results: 498 surgeons and 398 medical oncologists responded (60.5% response rate). We excluded 130 who did not see breast cancer pts. Respondents averaged 19 years in practice, 79% were male, 74% saw > 10 breast cancer pts/yr, and 45% offered same-day multi-specialty appointments. 84% of medical oncologists and 85% of surgeons reported discussing recurrence risk using terms such as “high risk.” Medical oncologists were much more likely than surgeons to use an online risk calculator (76 vs 24%, p < .001), provide numerical risk estimates (88 vs 47%, p < .001), and provide a copy of risk estimates (71 vs 17%, p < .001). Specialty (p < .01) and multidisciplinarity (p < .01) were the only significant independent correlates of communication practices. After controlling for specialty, clinicians offering same-day multi-specialty appointments were more likely to use online calculators (OR 1.6, 95% CI 1.1 - 2.3) and discuss numerical risk estimates (OR 1.8, 95% CI 1.2 - 2.5). Conclusions: Most medical oncologists use online calculators and numerical estimates to communicate recurrence risk to breast cancer patients; fewer surgeons do so. Patients who do not see a medical oncologist until after surgery may make critical treatment decisions (including whether to remove the contralateral breast) without full understanding of relevant risk information.
Feasibility of adjuvant carboplatin/docetaxel (C/D) in patients (pts) resected stage I-IIIB non-small cell lung cancer (NSCLC): Preliminary report of a phase II trial
Authors: T. E. Stinchcombe, M. A. Socinski, H. D. Harper, T. A. Hensing, D. Moore, J. M. Crane, J. N. Atkins, E. M. Willard, M. T. Tynan, S. E. Gulino
Journal: Journal of Clinical Oncology (2007)

18069 Background: Adjuvant cisplatin-based chemotherapy has been shown to improve survival in patients with resected NSCLC; however, compliance with chemotherapy has been problematic. Carboplatin (C) is better tolerated than cisplatin, and therefore may improve adjuvant chemotherapy compliance. C/D is a commonly used treatment for advanced NSCLC with an acceptable toxicity profile. Methods: Pts with resected NSCLC with a good functional status, preserved renal, hepatic, and bone marrow function were enrolled. Therapy was initiated 2–8 weeks from surgery, and consisted of 4 cycles C (AUC=6), and docetaxel (D) 75 mg/m 2 every 3 weeks. The primary end-point was the feasibility of delivering C/D. An “adequate exposure” was defined as receiving 4 cycles of C/D within 12 weeks of initiating therapy. A sample size of 72 pts provided 88% power to detect a true adequate exposure of rate of at least 80%. Results: 72 pts have been enrolled on the protocol, and 64 patients have completed therapy, 7 patients are currently receiving therapy, and data is incomplete on 1 patient. Pt demographics are: median age=65 years (range 47–84); gender: female 34%, male 66%, race: white 86%, African American 10%, other minorities 4%; performance status: 0 (38%), 1 (58%), 2 (1%), unknown (3%). The stage distribution was: I (41%), stage II (32%) stage IIIA (25%), stage IIIB (1%). To date, 45/64 pts (70%) have completed 4 cycles within 12 weeks, and total of 50 (78%) of pts completed 4 cycles within 14 weeks. 11 pts have had D dose reduced, and 2 pts have had C dose reduced. 35 pts (55%) completed the 4 cycles at full dose within 12 weeks, and 38 patients (59%) within 14 weeks. Reasons for discontinuing treatment: withdrew from treatment (n=3), withdrew consent prior to initiating therapy (n=2), disease progression (n=2, brain metastases), adverse events (n=5), complication of other medical conditions (n=1), unknown reasons (n=1). Therapy was well tolerated and no treatment-related deaths were observed. Conclusions: Preliminary results indicate that adjuvant therapy with CD results in a similar rate of chemotherapy compliance to that of cisplatin-based chemotherapy. No significant financial relationships to disclose.
Clinical benefit of zoledronic acid in patients with lung cancer and other solid tumors: Analysis based on prior history of skeletal complications
Authors: V. Hirsh, N. S. Tchekmedyian, L. Rosen, M. Zheng, Y. J. Hei
Journal: Journal of Clinical Oncology (2004)

7226 Background: We previously reported the efficacy and safety of 4 mg zoledronic acid in patients with bone metastases secondary to lung cancer or other solid tumors (Rosen et al. J Clin Oncol. 2003;21:3150–3157). We report here the results of a retrospective exploratory analysis to assess the risk of skeletal-related events (SREs) and the efficacy of 4 mg zoledronic acid compared with placebo based on patients' history of SREs prior to study entry. Methods: An SRE was defined as a pathologic fracture, spinal cord compression, radiotherapy or surgery to bone, or hypercalcemia. Patients were stratified based on their history of SREs before study entry, and the occurrence of SREs on study (over 21 months) was analyzed. Results: A total of 507 patients were randomized to 4 mg zoledronic acid or placebo; 131 completed the 9-month core phase, and 69 entered the 12-month extension phase. Before study entry, 347 (68%) of patients experienced at least 1 SRE, and these patients were at higher risk of developing an SRE on study than patients with no prior SRE (hazard ratio = 1.43). In the placebo group, 52% of patients with a prior SRE had at least 1 SRE on study compared with only 40% of patients with no prior SRE. Among patients with an SRE before study entry, Andersen-Gill multiple event analysis showed that zoledronic acid significantly reduced the risk of developing an SRE on study by 31% compared with placebo (risk ratio = 0.688; P = .009). Zoledronic acid also significantly reduced the mean skeletal morbidity rate (1.96 versus 2.81 SREs/year for placebo; P = .030) and prolonged median time to first on-study SRE by nearly 4 months (215 versus 106 days for placebo; P = .011). Among patients with no SRE before study entry (n = 156), zoledronic acid reduced the risk of SREs by 23% (P = .308), reduced the mean skeletal morbidity rate (1.34 versus 2.53 SREs/year for placebo; P = .332), and prolonged the median time to first SRE by 2.5 months (P = .534). Conclusions: This exploratory analysis demonstrates that patients with a history of SREs are at high risk of subsequent SREs, and zoledronic acid reduces skeletal morbidity regardless of a prior history of SREs. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pharmaceuticals Corp. Novartis
Clinical ethics consultation in oncology.
Authors: Andrew G Shuman, Sacha M Montas, Andrew R Barnosky, Lauren B Smith, David W Kissane, Joseph J Fins, Mary S. McCabe
Journal: Journal of Clinical Oncology (2012)

9121 Background: There is limited empirical research exploring the nature of clinical ethical consultations within the oncology population. Our objective is to review, describe and compare clinical ethics consultations at two NCI-designated comprehensive cancer centers, in order to identify opportunities for systems improvement in clinical care. Methods: This case series is derived from prospectively-maintained clinical ethics consultation databases at each institution. All adult oncology patients receiving ethics consultation from 2007 through 2011 were included as eligible cases. Both qualitative and quantitative analyses were undertaken. Demographic and clinical information were obtained from the databases for all patients, and verified via chart abstraction. Additional variables studied included the reason for and context of the ethical consultation, the patient’s code status before and after consultation, and involvement of palliative care or other adjuvant services. Opportunities for systems-level improvements and/or educational initiatives were identified. Results: A total of 207 eligible cases were identified. The most common primary issues leading to ethics consultation were code status and advance directives (25%), surrogate decision-making (17%), and medical futility (13%). Communication lapses were identified in 41%, and interpersonal conflict arose in 51%. Prior to ethics consultation, 26% of patients were DNR; 60% were DNR after ethics consultation. Palliative care consultation occurred in 41% of cases. Opportunities for systems improvement and professional education related to goals of care at the end of life, the role of palliative care involvement, and improved communication. Conclusions: Ethics consultations among cancer patients reflect the realities inherent to their clinical management. Appropriately addressing advance directives within the context of overall goals of care is crucial. Thoughtful consideration of communication barriers, sources of interpersonal conflict, symptom control, and end-of-life care are paramount to optimal management strategies in this patient population.
Differences in Stem Cell Collection Practices and Related Outcomes Between Centers That Conduct and Do Not Conduct Aphaeresis on Weekends
Authors: Nelson J. Chao, Lisa M Bernard, George Carrum, Henry C. Fung, Daniel T Grima, Leona Holmberg, Stephen Brown, Mitchell E. Horwitz, Junya Kanda, Jane L. Liesveld, Brian McClune, Paul Shaughnessy, Guido J. Tricot
Journal: Blood (2011)