tbuckley/cabot-search huggingface dataset:
Predictors of survival after trimodality therapy for esophageal adenocarcinoma: Analysis from the National Cancer Database.
Authors: Oliver Eng, Rebecca A. Nelson, Joseph Chao, Loretta Erhunmwunsee, Dan Raz, Jae Y. Kim
Journal: Journal of Clinical Oncology (2017)

116 Background: Trimodality therapy with neoadjuvant chemoradiation followed by surgery has been shown to improve survival compared to surgery alone for the treatment of locally advanced esophageal cancer, but there is considerable variation in survival in this population. We sought to analyze factors associated with survival after trimodality therapy in esophageal adenocarcinoma. Methods: We identified 4,679 patients from the National Cancer Database (NCDB) who received chemotherapy and radiation prior to surgery for esophageal adenocarcinoma from 2006-2013. Patients with stage IV disease and unknown pathological nodal status were excluded. We performed a multivariate analysis using a Cox proportional hazards model to identify independent predictors of overall survival. Results: On multivariate analysis, pathologic characteristics associated with decreased overall survival included stage, lymphovascular invasion, and positive surgical margins. Insurance status, age, and comorbidity index were also associated with decreased survival. We found that patients treated at academic programs (HR 0.85, CI 0.78-0.92, p=0.0001) and those who received additional adjuvant chemotherapy had improved survival (HR 0.86, CI 0.75-1.00, p=0.0452), but the vast majority of patients receiving trimodality therapy (4,306; 92.0%) did not receive adjuvant chemotherapy. Patients who received adjuvant chemotherapy were more likely to have private insurance (69 vs. 53%, p&lt;0.0001). Compared to private insurance, Medicaid (HR 1.43, CI 1.20-1.70, p&lt;0.0001), Medicare (HR 1.21, CI 1.07-1.36, p=0.0026), or having no insurance (HR 1.49, CI 1.16-1.90, p=0.0015) were all negative predictors of overall survival. Conclusions: There is wide variation in survival following trimodality therapy for esophageal adenocarcinoma. Both tumor characteristics and patient characteristics play a role. Adjuvant chemotherapy appears to be associated with improved survival, but only a minority of patients receive adjuvant chemotherapy in this setting. Insurance status and treatment setting are independent predictors of overall survival after trimodality therapy and may indicate treatment disparities.
A randomized 2×2 biomarker trial of low-dose tamoxifen and fenretinide in premenopausal women at-high risk for breast cancer
Authors: A. Decensi, B. Bonanni, A. Guerrieri-Gonzaga, C. Robertson, M. Cazzaniga, F. Mariette, M. Gulisano, A. Latronico, D. Franchi, K. Johnson
Journal: Journal of Clinical Oncology (2004)

1001 Background: Tamoxifen and fenretinide have been shown to reduce breast cancer incidence in pre-menopausal women at increased risk. Their combination is synergistic in reducing mammary tumor formation in animal models. Methods: We conducted a double-blind placebo controlled trial in women at high risk to determine whether there is an interaction between the two agents on putative breast cancer surrogate endpoint biomarkers. The primary outcome measures were the change in insulin-like growth factor-I (IGF-I) and in mammographic percent density after 2 years of intervention. Additional endpoints include changes in endometrial thickness and proliferation, presence of ovarian cysts and atypia in random fine needle aspirates. Results: Between October 1998 and April 2002, 235 women were randomized either to tamoxifen 5 mg/d, or fenretinide 100 mg bid, or both agents, or placebo for 2 years. Subjects were included because of a previously excised DCIS (57%), LCIS (13%), micro-invasive breast cancer (7%), or because of a 5-year Gail risk ≥1.3% (23%). The mean±SD age is 46.2±4.7 years and the mean±SD BMI is 23.5±3.5 kg/m2. Recruitment was prematurely stopped by the DSMB based on the lack of an interaction between agents on the primary endpoint biomarkers. After a median follow-up of 38 months, 40 subjects are still on treatment, 35 have dropped the study either for refusal (19) or adverse events (16). Two serious adverse events occurred: one stage I endometrial cancer in the fenretinide arm and one optic nerve ischemia in the tamoxifen arm. A preliminary safety analysis on endometrial effects showed no increase in endometrial thickness and no difference in endometrial polyps among the four arms. Twenty-seven primary or recurrent breast cancers have been observed. Treatment compliance as assessed by pill count and self-reporting show a greater than 80% adherence in >90% of the subjects. Conclusions: These data show that both agents are safe. Biomarker measurements are ongoing and preliminary results in terms of efficacy and safety will be presented at the conference. Supported by the NCI grant CA77188 No significant financial relationships to disclose.
Evaluation of the PI3K inhibitor BAY 80-6946 in hematologic malignancies.
Authors: Michael Jeffers, Ronald L. Dubowy, Chetan D. Lathia, Robert Mallon, Leonard Joseph Appleman, Ramesh K. Ramanathan, Amita Patnaik
Journal: Journal of Clinical Oncology (2012)

e13576 Background: BAY 80-6946 is a new investigational compound that potently inhibits all PI3K Class I isoforms. BAY 80-6946 is under phase 1 clinical evaluation and PRs have been observed in solid tumors (ST) and follicular lymphoma (FL). The present analysis was performed to gain mechanistic insights into the activity of this compound in FL and potentially other hematological malignancies. Methods: Preclinical: The growth-inhibitory activity of BAY 80-6946 on hematological cancer cell lines (n= 32) was determined by the CellTiterGlo assay. GS-1101 (formerly called CAL-101) and cisplatin (CP) were also tested. Clinical: Specimens from subjects enrolled in a BAY 80-6946 Phase 1 trial MTD expansion were used. Levels of various cytokines and chemokines were determined by ELISA or multiplex immunoassay in plasma samples (n= 27) obtained prior to and during BAY 80-6946 treatment of 6 subjects (3 FL + 3 ST). Proteins examined included CXCL13 (involved in B-cell homing) and BAFF (involved in B-cell survival). Tumor tissue was used to determine PTEN expression via IHC and the mutational status of PTEN via sequencing. PIK3CA mutational status was evaluated in tumor tissue and plasma via BEAMing. Results: Preclinical: BAY 80-6946 was more potent on B-cell lymphomas and other hematological cancer cell lines than GS-1101 or CP (median IC 50 in μM: BAY 80-6946= 0.49; GS-1101= 37; CP= 2.9). Clinical: Plasma levels of CXCL13 decreased and BAFF increased following BAY 80-6946 administration in all subjects examined (CXCL13 mean change: -58%; p= 0.004; BAFF mean change: +67%; p= 0.042). PTEN expression was lower in FL compared to ST. No mutations in PTEN or PIK3CA were identified in FL. Mutations in PIK3CA were identified in some ST. Conclusions: These preclinical results indicate that the observed early clinical activity of BAY 80-6946 in FL may be due to a direct anti-proliferative effect on malignant B-cells. The plasma chemokine/cytokine results support the possibility that the modulation of factors involved in B-cell homing and survival may play a mechanistic role in mediating this activity. Overall these results support the continued clinical evaluation of BAY 80-6946 in FL and other hematological malignancies.
Survival trends in palliative care patients with cancer: A Mayo Clinic 5-year review
Authors: A. H. Kamal, K. M. Swetz, H. Liu, S. R. Ruegg, E. C. Carey, K. Whitford, F. A. Bock, E. T. Creagan, T. J. Moynihan, J. S. Kaur
Journal: Journal of Clinical Oncology (2009)

9592 Background: Palliative care (PC) is an essential part of the continuum of care for cancer (CA) patients (pts). Little is known about the aggregate characteristics and survival of pts receiving inpatient palliative care consultation (PCC). Methods: We reviewed data prospectively collected on patients seen by the Palliative Care Inpatient Consult Service at Mayo Clinic - Rochester from 2003–2008. Demographics, consult characteristics, and survival were analyzed. Kaplan-Meier survival curves and a Cox model of survival were produced. Results: 1794 total patients were seen over the five year period. Cancer is the most common primary diagnosis (47%). Growth in annual PCC has risen dramatically (113 in 2003 vs. 414 in 2007) despite stable total hospital admissions. Patient are predominantly men (52% vs. 48%, p=0.02); median age is 76. General medicine, medical cardiology, and medical intensive care unit services refer most often. Most frequent issues addressed are goals of care, dismissal planning, and pain control (29%, 19%, 17%). PCC in actively dying pts have increased with 27% of all non-operating room, non-trauma in-hospital deaths being seen. Although CA pts have the highest median survival after PCC vs. other diagnoses (17 days, p = 0.018), we observed a five-year trend of decreasing survival from admission to death and PCC to death. Median time from admission to death in CA pts is 36 days in 2003 and 19 days in 2008 (p&lt;0.01). Median time from PCC to death is 33 versus 11.5 days (p&lt;0.01). Despite this, median hospital length of stay and time from PCC to discharge have remained fixed at 8 and 2.5 days, respectively. A Cox model of survival to discharge and &lt;6 months survival (hospice eligibility) shows hospital length of stay, time from consult to discharge, and dismissal location from hospital are all prognostic factors. Conclusions: Survival window for PC intervention for CA pts is lessening. With the trend of shorter survival after PCC, PC professionals have little over two days to implement a comprehensive, ongoing care plan. This highlights the importance of earlier outpatient palliative care involvement with advanced cancer patients and families. No significant financial relationships to disclose.
The role of panitumumab in combination with ECX in perioperative chemotherapy of unselected patients with locally advanced gastroesophageal adenocarcinomas: Randomized phase II study of the German Cancer Society.
Authors: Markus H. Moehler, Florian Lordick, Andre L. Mihaljevic, Stephan Kanzler, Thomas Hoehler, Peter C. Thuss-Patience, Stefan Paul Moenig, Volker Kunzmann, Sebastian Schroll, Hans-Joachim Meyer, Andreas Sandermann, Christoph Schumacher, Hansjochen Wilke, Andrea Tannapfel, Michael Stahl
Journal: Journal of Clinical Oncology (2015)

4040 Background: Perioperative chemotherapy (pCT) significantly improved survival of patients (pts) with locally advanced esophagogastric adenocarcinoma (la EGC). However, ~60% of pts will later die from their disease. Thus, targeted drugs are worthwhile to be investigated to further improve survival (OS). Methods: To evaluate the role of the EGFR-antibody panitumumab with pCT, we performed an open randomized phase II study in 22 German centres. Untreated pts with la EGC (cT3-4 N0-3 M0) were eligible and treated with standard ECX therapy with (arm 1 ) or without (arm 2) panitumumab (9 mg/kg body weight iv, q 3 weeks). Three cycles were given prior to and after surgery. 163 from 171 pts (83 arm 1, 80 arm 2) were eligible from 11/2010 to 7/2013. Results: Compliance and dose intensity of pCT was equal in both arms, however 49% started and only 31% completed postop. CT in arm 1 versus 50% and 40% in arm 2, respectively. The cumulative capecitabine dose was lower in arm 1 (58% vs. 70% of planned dose). No death was observed until 30 days after postop. CT. Local efficacy was slightly increased with panitumumab (75% vs. 68% without progression/death or with downstaging, p = 0.24). PFS (HR 1.21; 0.78-1.89) and OS (HR 1.30; 0.79-2.13) was not significantly lower in arm 1. Molecular analyses were possible in 76 / 163 pts (47%): c-MET overexpression was high (53%); however c-MET amplification (4%), EGFR-amplification or overexpression (7%), HER2-positivity (8%) or RAS-mutations (3%) were rarely observed. 117 plasma samples were analyzed for 25 EGFR signaling markers and ligands. At baseline, patients had slightly higher levels vs. healthy controls for BDNF , EGF, HGF, PDGF, PlGF, SCF, VEGF-A, and -D. Conclusions: Similarly to metastatic disease, adding EGFR-antibody panitumumab to ECX did not improve the results in unselected locally advanced EGC pts. The rare pt numbers with possible predictive molecular alterations made it unlikely to define subgroups who may have benefitted from the addition of panitumumab to perioperative CT. Clinical trial information: 2008-007798-18.
The Brazilian experience with biochemotherapy for metastatic melanoma: Long-term results in 163 patients.
Authors: Raphael Brandao Moreira, Renata D'Alpino D'Alpino, Tercia Tarciane Soares de Sousa, Aline Da Rocha Lino, Jessica Ribeiro Gomes, Marcus Paulo Fernandes Amarante, Carolina Kawamura Haddad, Rafael Schmerling, Fernando C. Maluf, Antonio C. Buzaid
Journal: Journal of Clinical Oncology (2015)

e20073 Background: The long term survival impact of biochemotherapy (BioCT) for patients with metastatic melanoma (MM) is not well established in the literature. We performed a retrospective analysis of MM patients treated with BCT under our care. Methods: This was a retrospective single-team experience of 163 consecutive patients who underwent BioCT from 1998 to 2014. BioCT consisted of cisplatin (20 mg/m2 IV D1-D4), vinblastine (1,6 mg/m² IV D1-D4), dacarbazine (800 mg/m2 IV D1), interleukin-2 (9 MU/m² IV over 24h D1-D4) and interferon-alpha (5 MU/m² SC D1-D5), with G-CSF (300 mcg SC D5- D14) every 3 weeks for a maximum of six cycles. Median progression-free survival (PFS) and overall survival (OS) were calculated by the Kaplan-Meier method. Results: All 163 patients (58.2% male) were included in the analyses. Median age was 47 (range 19-65). Overall response rate as determined by the local radiologist report was 52% (complete response [CR]: 19%; partial response: 33%). Median PFS was 5.0 months (95% confidence interval [CI] 3.6-6.4 months). Median OS was 19.7 months (95% CI 14.6-24.8 months). Five-year OS was 27.6% (95% CI 19.3-35.8%). Out of the 32 patients who achieved a CR, 8 (25%) were alive and with no evidence of disease at 5 years (5% of the entire cohort). Conclusions: Despite recent advances in the treatment of metastastic melanoma, BioCT remains a solid treatment alternative for MM with curative potential in a small fraction of patients.
Cancer patients’ attitudes, knowledge, and preferences for smoking cessation (SC).
Authors: Lawson Eng, Devon Alton, Tom Yoannidis, Qin Quinn Kong, Robin Milne, Samantha Sarabia, Zahra Merali, Liam Murphy, M Catherine Brown, John N. Waldron, Andrew Pierre, Andrea Bezjak, Andrew J. Hope, Doris Howell, Jennifer M. Jones, Peter Selby, Wei Xu, David Paul Goldstein, Meredith Elana Giuliani, Geoffrey Liu
Journal: Journal of Clinical Oncology (2015)

9581 Background: Smoking tobacco by cancer patients can lead to poorer treatment outcomes, prognosis and quality of life. We evaluated ambulatory cancer patients’ understanding of SC. Methods: 295 lung and head and neck cancer (HNC) patients (85% curative) at any point in their disease course were surveyed cross-sectionally about their knowledge on the effect of smoking on cancer treatment/prognosis and their interest/preferences towards SC. Multivariate logistic regression analyses identified predictors of knowledge gaps and interest in SC. Results: 52% of patients had HNC; 31% smoked at diagnosis, 35% were ex-smokers. Half of patients reported being unaware that continued smoking negatively impacts cancer surgery (48%), radiation (57%), chemotherapy (49%) and treatment efficacy (55%); some patients were unaware it impacted prognosis (38%) and second-primary risk (36%). This lack of knowledge was not associated with stage, specific treatments, or SC. Compared to HNC, lung cancer patients more likely believed that continued smoking negatively impacted surgery (aOR = 1.82, 95% CI[1.06-3.10]), efficacy (aOR = 2.10[1.26-3.50]), prognosis (aOR = 2.29[1.20-4.40]) and second-primaries (aOR = 2.02[1.05-3.89]). Receiving any recent (< 3 months) treatment was associated with believing that smoking negatively impacts treatment (aORradiation= 2.34[1.36-4.04], aORchemo= 1.73[1.05-3.44]). Although 75% felt a SC program would be beneficial and 67% felt it should be part of routine cancer care, only 43% of smokers at diagnosis wished to take part; mainly lung cancer patients (aOR = 5.14[1.79-14.80]) and early-stage cancer patients (aOR = 3.42[1.11-10.50]). 51% preferred discussing SC at their first visit, 52% through a smoking counsellor, and 93% preferred same-day programs with their clinic visits. 50% of patients uninterested in a SC program described wishing to quit on their own. Conclusions: Cancer patients undergoing treatment were more likely to feel that smoking can impact treatment; interventions during this time may improve SC rates. Compared to lung cancer, HNC patients were less aware of the impact of smoking on outcomes, and less interested in SC programs.
Interim analysis of a phase II trial of <i>nab</i>-paclitaxel in patients with very advanced relapsed/refractory multiple myeloma (RR-MM).
Authors: Allison Claire Rosenthal, Rafael Fonseca, Joseph Mikhael, A. Keith Stewart, Angela Mayo, Marta Chesi, Heidi Kosiorek, P. Leif Bergsagel
Journal: Journal of Clinical Oncology (2015)

e19537 Background: Nab-paclitaxel (Abraxane) has demonstrated anti-tumor activity in a murine model of MM. We report the results of a single arm phase II trial in RR-MM patients (pts). Methods: Eligibility criteria were: ≥ 18yo, M spike ≥ 1g/dL, > 200mg of monoclonal protein/24 hr UPEP, or serum FLC > 10mg/dL and abnormal kappa/lambda FLC ratio; ANC ≥ 500/mm³, platelets ≥ 25000/mm³, Hb ≥ 6 g/dL, Bili ≤ 2.5x ULN, AST/ALT ≤ 5x ULN, creatinine ≤ 3mg/dL; ≥ 3 prior therapies; negative pregnancy test. Treatment consisted of: 100mg/m2 nab-paclitaxel IV and dexamethasone 20mg on days 1, 8, and 15 (28d cycle) for up to 12 cycles. The primary endpoint was response rate. Results: Thirteen patients were enrolled (median age of 70 years; range 46-81) and 10 were male. Pts were heavily pretreated (average of 7.6 prior therapies; range 3-12) and were refractory to bortezomib (100%), lenalidomide (100%), pomalidomide (77%), and carfilzomib (84.6%). 10 patients had prior SCT. A quantifiable decline in serum FLC and M spike was seen in 6 patients. With 2.3 months of median follow up (range 0.7-13.2), 11 patients progressed. At interim analysis, 6 pts are alive and no pts remain on treatment. Median cycles: 2 (range 1-6). 9 pts (69.2%) discontinued treatment due to disease progression. 46% of pts had SD or better with one pt achieving a confirmed response (PR [cycle 1], VGPR [cycles 2-5]). PFS was 1.61 months. OS and TTP were 3.08 months (95% CI 1.67-NR) and 1.67 months respectively. Seven patients experienced a ≥ grade 3 AE at least partially related, including 1 death due to sepsis. Grade 4 toxicities included: neutropenia (n = 2, 15.4%), thrombocytopenia (n = 1, 7.7%), and febrile neutropenia (n = 1, 7.7%). Conclusions: While nab-paclitaxel did not reach the prespecified endpoint, it showed evidence of anti-MM activity. Patients treated in this protocol had very advanced disease and yet some displayed reductions in monoclonal proteins. These results are similar to comparable studies in fairly advanced populations such as other tubulin inhibitors. Nab-paclitaxel should be tested in earlier phases of the disease. Clinical trial information: NCT01646762.
Patterns of <i>KRAS</i>, <i>NRAS</i> and <i>BRAF</i> testing among patients with metastatic colorectal cancer in the EU5.
Authors: Kimberly Lowe, Xin Niu, George Kafatos, Michael Anthony Kelsh
Journal: Journal of Clinical Oncology (2017)

637 Background: In mid-2013, the requirement for mCRC patients treated with panitumumab changed from wild-type KRAS to wild-type RAS ( KRAS and NRAS). The objective of this study was to describe patterns of KRAS, NRAS, and BRAF testing among mCRC patients in the EU5 (United Kingdom (U.K.), Germany, France, Italy and Spain). Methods: This descriptive study utilized Oncology Analyzer data (IMS Health Oncology, Fairfield, CT, USA), which provides real-world quarterly cross-sectional, epidemiologic and clinical data for mCRC patients. Trends in biomarker testing during the study period were evaluated by calculating the frequencies and proportions of patients who were /were not tested for combinations of KRAS, NRAS, and BRAF within each of the five countries. KRAS and BRAF data were available in all countries from quarter three (Q3) 2012 to quarter two (Q2) 2015. NRAS was available in all countries from quarter 1 (Q1) 2014 to Q2 2015. Frequencies and proportions were also calculated to summarize patient demographic and clinical characteristics between groups with different testing choices. Results: A total of 32,961 patients with mCRC were included in the analyses. Prior to 2013, the majority of patients in each country were tested for only KRAS. The proportion of patients tested for both KRAS and NRAS increased substantially during the period of data availability for NRAS (Q1 2014 to Q2 2015), including &lt;1% to 19.1% in the U.K., 8.8% to 31.9% in France, 13.1% to 43.2% in Germany, 5.9% to 24.6% in Italy, and 8.7% to 31.4% in Spain. The proportion of patients who were tested for all three biomarkers also increased during the period of data availability for all three biomarkers (Q1 2014 to Q2 2015), including 2.3% to 16.4% in the U.K., 4.8% to 26.6% in France, &lt;1% to 2.4% in Germany, 4.2% to 22.3% in Italy, and 1.5% to 9.3% in Spain. There were few differences in patient demographic or clinical characteristics between those with different testing groups. Conclusions: This analysis provides a description of biomarker testing using read-world data and suggests an overall increase in testing among mCRC patients in the EU5. Although there was a trend towards increased testing, many mCRC patients are still not tested for these important biomarkers.