tbuckley/cabot-search huggingface dataset:
Relationship between obesity and survival in advanced breast cancer.
Authors: Nicolas Castagneris, Matias Nicolas Cortes, Eduardo Richardet, Martin Eduardo Richardet, Perelli Laura, Matias Molina
Journal: Journal of Clinical Oncology (2012)

e11044 Background: Breast cancer is the second cause of cancer-related deaths. Obesity is defined as an excessive accumulation of fat. The body mass index (BMI) indicates relationship between weight and height and is used to identify obesity, which is associated with increased risk of cancer. Studies have shown the worst prognosis of obese patients undergoing adjuvant therapy. This paper aims to assess progression-free survival (PFS) and overall survival (OS) in relation to BMI, in patients with advanced breast cancer. Methods: We retrospectively analyzed medical records of 132 patients treated in the IONC from 2005 to 2010. We divided the patients into two groups: group A, BMI &lt;30 (not obese), Group B, BMI ≥ 30 (obese). Analysis of SG and TLP were estimated by the Kaplan-Meier method and compared using the log-rank test. Results: The PFS for group A was 16.44 months, and for group B it was 13.08 (p = 0.40). OS was 31.93 and 27.12, respectively (p = 0.31). Regarding BMI and menopausal status, we observed a marked increase in survival for non-obese premenopausal patients with statistical significance. See table below. Conclusions: Patients with BMI &lt;30 had higher survival rates, without reaching statistical significance. This could be due to small sample size and heterogeneity. Another relevant finding is the statistically significant difference in survival that favors premenopausal patients with lower BMI, which raises an area to be studied. This work demonstrates the importance of guiding patients towards a healthier life habit. [Table: see text] [Table: see text]
Evaluation of two different doses of weekly nab-paclitaxel (NP) in older breast cancer (BC) patients (pts).
Authors: Laura Biganzoli, Laura Orlando, Alessandro Minisini, Mirco Pistelli, Simon Spazzapan, Edda Simoncini, Elena Rota Caremoli, Silvana Assunta Leo, Daniela Baldari, Elena Zafarana, Palma Fedele, Emanuela Magnolfi, Lorenzo Pavesi, Antonella Brunello, Annamaria Molino, Sabino De Placido, Daniela Tomcikova, Angelo Di Leo, Fabio Puglisi
Journal: Journal of Clinical Oncology (2015)

9531 Background: NP compares favorably with conventional taxanes in terms of safety, efficacy and convenience of administration. These features make NP an interesting agent for evaluation in elderly pts. Methods: Pts aged ≥ 65 years (y) with HER2-negative (or HER2-positive but with contraindication to anti-HER2 therapy) advanced BC are randomized to receive as first-line chemotherapy NP at either 100 (Arm A) or 125 mg/m2 (Arm B), days 1, 8, 15 q 28 until an event (defined as progressive disease, functional decline or death) unacceptable toxicity (tox) or maximum benefit according to the Investigator. Due to the absence of prospective data on weekly NP in older BC pts, compliance and adverse events (AE) data in this population, even if preliminary, are clinically relevant and are reported in the present analysis. Results: 81 pts have been randomized so far. Evaluable for the present analysis are 44 pts who have received ≥ 1 cycle of NP and have a documented interruption of study treatment. Pts’s median age is 75y (65-84) in Arm A and 74y (65 -82) in Arm B. ECOG Performance status is 0 in both arms. No impairments in Instrumental Activities of Daily Living is reported in 16 pts in both arms. Median number of affected domains at Cumulative Illness Rating Scale-Geriatric is 2 with range 0-3 in Arm B and 0-4 in Arm B. Treatment’s compliance and safety data are reported in the Table. Conclusions: Both doses of weekly NB can be safely administered to older BC pts. Fatigue and neurotoxicity are the most frequently reported AE in both arms. Only 1 patient experienced G4 non hematological tox. Clinical trial information: 2012-002707-18. Arm A Arm B N. pts 23 21 Total/median n. cycles (range) 131/5 (2-19) 119/6 (1-10) Pts/cycles with dose reduction (%) 17 (74)/39 (30) 15 (71)/54 (45) Pts/cycles with delay (%) 7 (30)/13 (10) 8 (38)/13 (10) AE (CTC v4.0 criteria) occurring, if grade (G)2 in > 1 pt N.pts (%) G G 2 3 4 2 3 4 Anemia 6(26) - - 8(38) - - Leucopenia 6(26) - - 8(38) 4(19) - Neutropenia 5(22) 3(13) - 2(10) 8(38) 1(5) Infection 2(9) - - 1(5) - - Nausea 3(13) - - 5(24) - - Vomiting 1(4) - - 2(10) - - Stipsis 3(13) - - 3(14) - - Diarrhoea 1(4) - - 2(10) 1(5) - Anorexia 1(4) - - 2(9) - - Fatigue 5(22) 1(4) 1(4) 11(52) 3(14) - Neurotoxicity 1(4) 2(8) - 10(48) 2(10) - Myalgia 2(8) 1(4) - 1(5) - -
Rapid decrease in blood flow (BF), blood volume (BV), and vascular permeability (PS) in carcinoid patients treated with bevacizumab
Authors: J. C. Yao, C. Charnsangavej, S. C. Faria, J. Szklaruk, H. Chen, P. Hoff, A. Phan, S.-C. J. Yeung, J. L. Abbruzzese, J. A. Ajani
Journal: Journal of Clinical Oncology (2004)

3013 Background: Carcinoid tumors are vascular and frequently express VEGF. Effective systemic therapy is lacking. VEGF neutralizing antibodies decrease metastases in a carcinoid xenograft model. We are evaluating anti-angiogenic therapy in a phase II study of bevacizumab (BVZ) and PEG interferon alpha-2b (PEGI) in patients with metastatic or unresectable carcinoid tumors. Methods: Patients on a stable dose of octreotide are randomly assigned to BVZ or PEGI for 18 weeks. After initial 18 weeks, patients receive both BVZ and PEGI. Planned accrual is 44 patients. Functional CT (fCT) is used to monitor BF, BV, and PS. Results: Sixteen patients have been accrued; 8 patients have begun treatment on each arm. Radiological responses (1 PR and 1 MR) have been observed on BVZ therapy. One additional patient with SD had a 78% drop in urine 5HIAA level. Baseline and follow-up scans obtained 48 hours after the first dose of BVZ are being reported in the analysis of antiangiogenic effects. Rapid declines in tumor BF, BV, and PS were observed (Table). No significant change in mean transit time was observed. First follow-up fCT on the PEGI arm is performed at week 9. Due to the differing follow-up schedule, fCT data on the PEGI arm is available on only 2 patients at this time. No significant changes in BF, BV, and PS were observed. All patients remain on study and accrual is on going. Conclusions: BVZ treatment in carcinoid patients consistently produced rapid decline in tumor BF, BV, and PS. fCT in carcinoid may be an effective and non-invasive method for assessing target inhibition in VEGF directed anti-angiogenic therapy. No significant financial relationships to disclose.
The influence of BRCA variants of uncertain significance in cancer risk management decision-making.
Authors: Jing-Yi Chern, Sarah S. Lee, Melissa K Frey, Rebecca Bassett, Jessica Martineau, Stephanie Blank
Journal: Journal of Clinical Oncology (2015)

1555 Background: Among patients undergoing genetic testing for BRCA1/2 mutations, 7% will harbor a variant of uncertain significance (VUS), a finding with more emotional than clinical weight. The objective of this study was to compare cancer risk management decisions among women with BRCA VUS to those of women with negative results. Methods: Between 1/2006-12/2012, we identified patients whose genetic testing results yielded a VUS and those who had definitively negative results at a single institution. VUS patients were matched with negative patients of the same age and testing date. χ2analyses were used to assess differences between the groups. Results: Three hundred and seventy-one patients underwent genetic testing during the study period. Eighty-two (22%) patients had a VUS and were matched with 82 control patients with negative genetic testing. The median age of study patients was 47 years for the 164 patients evaluated. Women with a VUS were more racially diverse than those with negative testing (38 of 82, 46% non-Caucasian vs. 16 of 82, 20%, p= 0.002). VUS patients were less likely to be of Ashkenazi descent (14 of 82, 17% vs. 32 of 82, 39%, p= 0.002). Patients with VUS were more likely to be referred to a gynecologic oncologist (42 of 82, 51% vs. 29 of 82, 35%, p= 0.058). Among VUS patients, 21% (17 of 82) were recommended to undergo ovarian cancer screening and 28% (23 of 82) risk-reducing bilateral salpingo-oophorectomy (RRBSO) vs. 15% (12 of 82) and 28% (23 of 82), respectively, for controls (p = 0.28). Ultimately, RRBSO was performed in 20% (32 of 164) of all patients, with no significant difference in rate of surgery based on the presence of a VUS. Conclusions: At our institution, patients with VUS are managed similarly to those with negative BRCA testing. In these groups of patients, screening and prevention strategies need to be individualized. The numbers of patients with VUS are likely to increase with the implementation of multi-gene testing. Our findings underscore the importance of genetic counseling in the management of genetic testing results.
Interaction between regorafenib and warfarin therapy.
Authors: Muhammad S. Beg, Leticia Khosama, Stefanie Conley, Yull Edwin Arriaga, Samira K. Syed, Sirisha Karri, Udit N. Verma
Journal: Journal of Clinical Oncology (2017)

651 Background: Regorafenib is an oral multi kinase inhibitor with clinical activity in colorectal cancer, gastrointestinal stromal tumors and hepatocellular cancer. Drug- drug interactions are commonly encountered in clinical practice and warfarin continues to be the most commonly prescribed anticoagulant among cancer patients in the clinic. The interaction of regorafenib with warfarin has not been studied. Methods: Patients at a single institution being prescribed regorafenib were identified and charts reviewed for concurrent warfarin therapy. Baseline characteristics, indications for regorafenib and warfarin therapy was determined. Patients were followed up to the first 8 weeks of combination therapy. Results: We identified 6 patients on concurrent regorafenib and warfarin. All patients had refractory colon cancer. Median age was 74, 4 were male and 5 white. Indication for warfarin was venous thromboembolism in 5 and atrial fibrillation in 1. Baseline INR ranged from 1.1 to 2.4. An increase in INR was seen in all six patients (peak INR range 4.5 to &gt; 12) which improved with dose modification. Time to peak INR was less than 6 weeks (INR trends in all patients shown in figure 1). There were no bleeding complications noted in any patient. Conclusions: We report a clinically significant interaction between warfarin and regorafenib with patients demonstrating an increase in INR. Patients who are anticoagulated with warfarin and start regorafenib should be closely monitored and upfront warfarin dose reduction should be considered. Further drug-drug interaction studies are needed to determine the exact mechanism of drug-drug interaction between these medications.
Romidepsin (FK228), a histone deacetylase inhibitor: Final results of a phase II study in metastatic hormone refractory prostate cancer (HRPC)
Authors: C. Parker, R. Molife, V. Karavasilis, A. Reid, S. G. Patterson, C. Riggs, C. Higano, W. M. Stadler, W. McCulloch, J. S. de Bono
Journal: Journal of Clinical Oncology (2007)

15507 Background: Romidepsin is a bicyclic depsipeptide that inhibits histone deacetylase (HDAC). Translocations fusing TMPRSS2 gene and ERG oncogenic factor is associated with elevated HDAC-1 expression. HDAC inhibition results in accumulation of hyperacetylated histone proteins resulting in G1 and G2/M arrest, differentiation of transformed cells and apoptosis. Romidepsin can also inhibit HSP90, ablating androgen receptor expression. This is the 1st study to report activity of an HDAC inhibitor in HRPC. Methods: Romidepsin was administered intravenously at 13mg/m 2 on days 1, 8 and 15 of a 28-day schedule. A 2-stage design was used. Eligibility criteria included: no prior chemotherapy, metastatic disease, QTcB &lt;470msec, Karnofsky PS =80. The primary endpoint was to determine rate of disease control (complete response [CR], partial response [PR], stable disease [SD] for 6 months). Secondary endpoints were PSA response rate (RR), time to PSA and objective disease progression, safety profile, effect on disease related symptoms and pharmacokinetics (PK) of romidepsin. Results: Thirty-one patients were enrolled. Median age: 64 years (range 43–82). Twenty-one patients are evaluable for radiological and PSA response: 1 patient achieved a confirmed radiological PR lasting &gt;6 months (m), and 2 confirmed SD for 6m. Four patients had SD lasting 5m (n=2) and 4m (n=2). The PSA RR was 7%. A 3 rd patient had a 40% fall in PSA lasting 5m. The most common drug related adverse events were (all grades, %): nausea (84%), fatigue (77%), vomiting (65%), anorexia (61%), constipation (45%), dysguesia (35%), diarrhea (32%), thrombocytopaenia (32%), anemia (28%) and neutropenia (25%). There were no grade 4 events. Non-specific asymptomatic ST segment changes on ECG were seen in 15 % of patients; there was no evidence of significant QTc prolongation on ECG confirmed by manual calculation. Conclusions: Treatment with single agent romidepsin is associated with a disease control rate of 14% and a PSA RR of 7%. Constitutional toxicities are prominent, no grade 4 events have been observed and only minimal cardiac toxicity has been reported. Further investigation in combination with other active agents in HRPC is warranted. [Table: see text]
Assessment of quality of life (QOL) in MA.17, a randomized placebo-controlled trial of letrozole in postmenopausal women following five years of tamoxifen
Authors: T. Whelan, P. Goss, J. Ingle, J. Pater, L. Shepherd, M. Palmer, D. Tu, N. Robert, S. Martino, H. Muss
Journal: Journal of Clinical Oncology (2004)

517 Background: The NCIC CTG MA.17 demonstrated substantial improvement in DFS by administering letrozole after 5 years of adjuvant tamoxifen to postmenopausal women with early stage breast cancer. An increase in low-grade hot flashes, arthritis, arthralgias and myalgias were identified in patients treated with letrozole. The objective of this sub-study was to evaluate QOL. Methods: Patients completed the Medical Outcomes Study 36 Item Short Form General Health Survey (SF36) and the Menopause Specific QOL (MENQOL) questionnaire at baseline, six months and annually. Mean change scores from baseline were compared between letrozole and placebo for summary measures and domains. The proportion of patients who demonstrated a minimally important worsening in QOL (defined as a difference from baseline of 5 points for SF36 and 0.5 for MENQOL) was also compared. An alpha of 0.01 was used in view of multiple comparisons. The analysis was limited to the first 3 years. Results: Of 5,187 women enrolled, 3,582 participated in the QOL sub-study. Baseline scores on the SF36 physical and mental health summary measures were similar to healthy populations and decreased over time in both groups. There were no significant differences between groups in mean change scores at 6, 12, 24 and 36 months. Small [<0.1 standard deviation (SD)] but statistically significant differences were seen for SF36 physical functioning (6, 12 months), bodily pain (6 months), vitality (6, 12 months) and MENQOL physical domains (12 months). Moderate (0.2–0.3 SD) differences were observed for the MENQOL vasomotor (6, 12, 24 months), and sexual domains (12, 24 months). Absolute increases in % of patients reporting worsening in their QOL at any time on letrozole compared to placebo for the different domains were: SF36 physical functioning (6%, p < .001); bodily pain (5%, p=.001); vitality (5%, p=.005); MENQOL vasomotor (8%, p< .001); physical (5%, p=.004); and sexual (4%, p=.02). Conclusions: Letrozole did not have a substantial adverse impact on QOL. Small effects were seen in some domains consistent with a minority of patients experiencing adverse effects. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis
VXM01, an oral T-cell vaccine targeting the tumor vasculature: Results from a randomized, controlled, first-in-man study in pancreatic cancer patients.
Authors: Friedrich Hubertus Schmitz-Winnenthal, Lars Grenacher, Tobias Friedrich, Heinz Lubenau, Marco Springer, Klaus M. Breiner, Nicolas Hohmann, Walter E. Haefeli, Gerd Mikus, Juergen Weitz, Alexis Ulrich, Markus W. Büchler, Philip Knebel, Thomas Schmidt, Yingzi Ge, Andreas G. Niethammer, Philipp Beckhove
Journal: Journal of Clinical Oncology (2013)

3090 Background: VXM01 is an orally available, bacterially transmitted DNA vaccine targeting VEGFR-2. Pre-clinically, VXM01 showed anti-tumor activity in multiple tumor types. This first-in-human study was designed to evaluate the safety and tolerability of VXM01. Secondary endpoints included VEGFR-2 specific T-cell responses, tumor perfusion changes, and related biomarkers. Methods: A randomized, double-blinded, placebo-controlled, dose-escalation study was conducted in 45 patients with advanced pancreatic cancer. VXM01 or placebo was given on days 1, 3, 5, and 7. Doses were escalated from 10(6) CFU to 10(10) CFU over 5 dose groups, each including 6 VXM01 and 3 placebo patients. VEGFR-2 specific T-cell activity was monitored by ELISpot and T(reg) specificity assays before, during and after the vaccination course. Tumor perfusion was assessed by DCE-MRI on days 0 and 38. Biomarkers included CA19-9, VEGF-A and collagen IV. Results: Patients were enrolled from 12/2011 to 10/2012. Most commonly observed AEs were leukopenia, abdominal pain, and diarrhea, which were all equally distributed between treatment and placebo group. While a mild elevation in average blood pressure was observed in the VXM01 group over the placebo group, the hypertension adverse event rate did not differ between both groups. No DLTs were observed. VEGFR-2 specific effector T-cell response was increased in 57% of evaluable VXM01 treated patients, during and after the vaccination course. In 25% of the VXM01 group, the T-cell response score post-vaccination was higher than maximum placebo levels. In contrast, VEGFR-2 specific T(reg) responses were overall reduced in vaccinated patients. DCE-MRI data indicated a &gt;33% drop in K(trans)/tumor perfusion in 35% of evaluable VXM01 treated patients vs. 10% in the placebo group. Mean changes were -4% (VXM01) and +15% (placebo). Reduced tumor perfusion correlated with VEGFR-2 specific T-cell responses and biomarker responses. Conclusions: VXM01 appeared safe and was well tolerated without DLTs across 5 tested dose levels. The data suggest further that VXM01 induces and enhances a VEGFR-2 specific T-cell response and impacts tumor perfusion. Clinical trial information: ISRCTN68809279.
Integrated somatic subtypes of localized intermediate-risk prostate cancer.
Authors: Natalie S Fox, Emilie Lalonde, Julie Livingstone, Julia Hopkins, Yu-Jia Shiah, Vincent Huang, Takafumi Yamaguchi, Veronica Sabelnykova, Lawrence Heisler, Michael Fraser, Theodorus van der Kwast, Robert G. Bristow, Paul Christopher Boutros
Journal: Journal of Clinical Oncology (2017)

e560 Background: Approximately two thirds of intermediate risk prostate cancer patients are over- or under- treated because we cannot correctly prognose this risk group; therefore we require novel biomarkers to better direct patient therapies and avoid subjecting patients to side effects without benefit. One reason genomic biomarkers are not currently used in clinical settings is because they are notoriously difficult to validate in follow-up studies. Furthermore, the lack of clear prostate cancer subtypes prevents the development of subtype specific biomarkers as is standard practice in breast cancer. We aim to improve biomarker validation rates by defining prostate cancer subtypes that can be used to create subtype specific biomarkers. Methods: First, we assess large scale genomic patterns using whole genome sequencing and methylation data and create integrative subtypes for intermediate risk prostate cancer. Second, we assess associations between specific aberrations and subtypes, and determine whether certain types of molecular aberrations are more important background aberrations for subtype specific biomarker development. Finally, we assess biases in prognostic performance of the published Lalonde biomarker between groups associated with patient subtypes to show that subtype aware biomarkers are necessary. Results: We demonstrate that the Lalonde biomarker is biased by the cohorts’ proportion of TMPRSS2-ERG (T2E) aberrations illustrating the need to develop different biomarkers for patients with T2E and patients without T2E. Further, we suggest integrative subtypes can be used to select patients with similar genomic profiles for biomarker analysis to improve biomarker validation rates. Conclusions: This analysis provides direct guidance for future biomarker development and addresses an important barrier to clinical use of genomic biomarkers for prostate cancer.
Other Malignancies in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL): Analysis of 2083 Patients.
Authors: Apostolia-Maria Tsimberidou, Susan O’Brien, Peter McLaughlin, Sijin Wen, William Wierda, Hagop M. Kantarjian, John Manning, Susan Lerner, Mark Hess, Emil J. Freireich, Michael J. Keating
Journal: Blood (2006)
A phase II study of pazopanib (GW786034) in patients with stage IV non-small cell lung cancer that have failed at least two prior chemotherapy regimens.
Authors: Sachdev P. Thomas, Timmy-Tai A Ho, Kathryn L Jackson, Pankaj Kumar, Patrick Leigh Gomez, Jamie Harper, Nancy Williams, Morgan N Medus, James Lloyd Wade
Journal: Journal of Clinical Oncology (2014)

e19008 Background: Pazopanib is a novel, orally active, small molecule inhibitor targeting multiple tyrosine kinases and is indicated for the treatment of advanced renal cell cancer and advanced soft tissue carcinoma. Based on preliminary efficacy data, we evaluated the activity and tolerability of pazopanib in non-small cell lung carcinoma [NSCLC] patients [pts]. Methods: Stage IV NSCLC pts were treated with 800 mg daily dose of pazopanib on days 1-21 of each cycle until progressive disease or unacceptable toxicity for a maximum period of 2 years following registration. Adverse events (AE’s) were graded by NCI-CTCAE v3.0. Treatment response was evaluated by investigators every 6 weeks or until progressive disease as demonstrated by RECIST 1.0 criteria. The primary outcome of the study was disease control rate (DCR) [complete response + partial response + stable disease]. Results: Total of 44 pts were screened, 33 pts were enrolled, and 32 pts [31% squamous (Sq) and 69% non-squamous (NSq)] were evaluable. 40% of enrolled pts were male and median age was 72. Median number of prior regimens was 2 (2-6). Grade ≥3 AE’s were seen in 84% of pts, with common drug-related grade ≥3 AE’s being: fatigue (50%), lymphopenia (31%), hypocalcemia (18%), and hypertension (18%). 41% of pts required at least 1 dose reduction due to AE’s, 15% discontinued treatment as a result of unacceptable toxicities, and there was 1 treatment-related death. After a dose reduction to 600 mg PO qday, there was a significant reduction in the severity and number of AE’s. The study demonstrated a DCR of 38% (95% CI 21-56%) in the entire pt population and 52% (95% CI 31-73%) in those who completed at least 12 weeks of therapy. Overall response rate was 16% (16% partial response). The median overall survival was 26.4 weeks (95% CI 16.1-37.9). The median progression-free survival was 14 weeks (95%CI 6-18). The overall survival between Sq and NSq pts was not significantly different. Conclusions: This trial demonstrates efficacy of Pazopanib in stage IV NSCLC [Sq & NSq] pts that have failed prior treatments. In this population, 600 mg PO qday is better tolerated. Clinical trial information: NCT01049776.