tbuckley/cabot-search huggingface dataset:
Population-based economic impact of nab-paclitaxel plus gemcitabine in metastatic pancreatic cancer.
Authors: Dejan Milentijevic, Gary Binder, Scott Whiting, Darryl Neil Penenberg, Xinyu Wei, Louis Kayitalire, Markus Frederic Renschler
Journal: Journal of Clinical Oncology (2014)

16 Background: Increasingly, assessing the quality of cancer treatment involves scrutiny of both outcomes and economics, particularly for advances in areas where generic agents have been standards of care. With nab-paclitaxel plus gemcitabine (nab-P/G) demonstrating a significantly improved updated median overall survival in first-line metastatic pancreatic cancer (1mPanc) patients (pts) vs gemcitabine (G) monotherapy (8.7 vs 6.6 months), this analysis aims to estimate the economic impact for a US health plan population, from adding nab-P/G as a treatment option for this condition. Methods: A three-year budget impact model was constructed to estimate 1mPanc costs for nab-P/G, G, gemcitabine + erlotinib (EG), other G combinations (OG), and FOLFIRINOX (F), from a US health plan perspective in 2013 US dollars. Inputs for prevalence, drug, administration, G-CSF, and adverse events were derived from SEER, prescribing information, publications, 3Q2014 Medicare reimbursement rates, and other public sources. The model used 2013 patient treatment mix rates as reported by Cartwright et al (ASCO 2013) with nab-P/G growing to 25% by 2015. Results: A population mirroring the US age mix would have 7 pts with 1mPanc annually per 100,000 lives. Treatment mix for 2013 was 27% F, 8% nab-P/G, 51% G, 8% EG, and 6% OG. Total costs per course of therapy per patient (pt) are shown in table. Baseline (before nab-P/G) population costs per 100,000 lives were $111,400 ($15,914 per average pt). Adding nab-P/G to the treatment mix for 1mPanc added $6,083 to population costs ($869 per average pt) for 2013, rising to $20,117 ($2,874 per average pt) for 2015 vs the baseline. Conclusions: Adding nab-paclitaxel plus gemcitabine as a treatment option for first-line metastatic pancreatic cancer pts was estimated to increase costs by 12% (about $2000 per average pt per year) over a three year period. The principal cost drivers were replacement of generic gemcitabine monotherapy, partially offset by savings from replacing FOLFIRINOX. [Table: see text]
Gender related survival differences associated with polymorphic variants of estrogen receptor beta (ERβ) and epidermal growth fact receptor (EGFR) in patients with metastatic colon cancer
Authors: O. A. Press, W. Zhang, D. Y. Yang, J. Yun, M. Gordon, D. Vallböhmer, K. E. Rhodes, S. Iqbal, H.-J. Lenz
Journal: Journal of Clinical Oncology (2005)

3590 Background: The Women’s Health Initiative has shown conclusively that estrogen has a protective effect against colon cancer. ERβ is expressed in the colon and loss of expression is associated with malignant transformation. The ERβ gene contains a polymorphic dinucleotide CA repeat in the 3’ noncoding region which is associated with hormone levels in females. Expression of ER is inversely correlated with EGFR, which is an independent prognostic marker for colon cancer. A single nucleotide polymorphism of EGFR with an amino acid substitution at codon 497 causes attenuated function of ligand binding. Polymorphisms of ERβ and EGFR were determined to establish clinical significance in patients with metastatic colon cancer. Methods: Genomic DNA from blood of 313 metastatic colon cancer patients, 176 males and 137 females, collected from 1997 to 2003 was analyzed for the CA repeat polymorphism in the ERβ gene and the EGFR codon 497 polymorphism. Conclusion: Males with metastatic colon cancer and the ERβ polymorphism having at least one allele with < 22 CA repeats have significantly better OS than those with both alleles ≥ 22 CA repeats. In women the opposite is true. Males with an A allele of EGFR-497 have significantly better OS when compared to GG allele. In females the opposite is true. This data supports the role of polymorphisms of ERβ and EGFR as independent prognostic markers in female and male patients with metastatic colon cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Chiron, Genentech, Response Genetics Lilly Oncology, Pfizer, Roche, Sanofi NCI, NIH
NeuACT, a phase II, randomized, open-label trial of DN24-02: Updated analysis of HER2 expression, immune responses, product parameters, and safety in patients with surgically resected HER2+ urothelial cancer.
Authors: Dean F. Bajorin, Padmanee Sharma, Leonard G. Gomella, Elizabeth R. Plimack, Peter H. O'Donnell, Jean H. Hoffman-Censits, Thomas W. Flaig, David I. Quinn, Robert Brownell Sims, Michael Locker, Nadeem A. Sheikh, Todd DeVries, Seth P. Lerner
Journal: Journal of Clinical Oncology (2014)

296^ Background: DN24-02 is an investigational autologous cellular immunotherapy (ACI) consisting of antigen presenting cells (APCs) cultured with BA7072, a recombinant HER2-derived antigen (HER500) linked to granulocyte-macrophage colony-stimulating factor. In the ongoing NeuACT (N10-1; NCT01353222) trial, patients (pts) with high-risk, HER2+ urothelial cancer (UC) are randomized 1:1 to either adjuvant DN24-02 or surveillance. Updated analyses are presented. Methods: Eligibility criteria include radical surgical resection of primary ≥pT2 or pN+ UC (bladder or upper tract) with HER2 expression ≥1+ by immunohistochemistry. Pts randomized to DN24-02 undergo 3 cycles of leukapheresis and infusion at 2-week intervals. Product potency is assessed at each infusion. Immune responses and adverse events (AEs) are measured at multiple time points. Results: By July 2013, tumor specimens from 226 pts had been screened. Of these, 75% (95% CI 69–81%) had HER2 expression of ≥1+ in the primary tumor, 32% had ≥2+ and 8% had 3+. In pts with available lymph node samples (n=83), 84% (95% CI 75–91%) had a HER2 score of ≥1+ in the lymph nodes; 49% and 14% had ≥2+ and 3+, respectively. Pts with 1+ HER2 expression had similar immune responses to BA7072 as those with higher HER2 levels. APC activation (CD54 upregulation) was observed at each infusion in the first 30 pts who had completed the 3 infusions, but was typically greater at infusions 2 (median 15.56; range: 6.42–23.97) and 3 (14.69; 8.24–30.86) than infusion 1 (7.35; 4.04–14.34). In the 5 pts with available data, BA7072 and HER500 specific antibody responses increased from baseline for at least 12 months. Most (92.3%) AEs were grade 1–2 in severity, including all AEs that occurred ≤1 day after infusion. Conclusions: The high frequencies (≥75%) of ≥1+ HER2 scores in primary tumor and lymph node samples confirm that HER2 expression is common in muscle-invasive and node+ UC. DN24-02 product potency data suggest an immunologic prime-boost effect. The observed humoral responses are the first data suggesting prolonged immune responses with an ACI in UC. Most AEs were grade 1–2 in severity. Clinical trial information: NCT01353222.
BRCA1 expression evaluated by real-time reverse transcriptase polymerase chain reaction (RT-PCR) in operable breast cancer.
Authors: P. Potemski, E. Pluciennik, A. K. Bednarek, R. Kusinska, S. Debska, R. Kubiak, R. M. Kordek
Journal: Journal of Clinical Oncology (2010)

10608 Background: BRCA1 plays an important role in regulation of DNA repair. Its loss-of-function mutations are the cause of hereditary breast cancer and are also frequently observed in basal-like breast cancer. However, little is known about relationship between mRNA-BRCA1 level and patient outcome. The aim of this study was to evaluate the relationship of BRCA1 expression to overall survival and to some clinical and pathological parameters i.e. age, tumor size, lymph node involvement, ER and HER2 expression, tumor grade, basal cytokeratin (CK5/6, CK17) and cyclin E expression. Methods: This was a retrospective study of 116 patients with ductal invasive breast cancer after radical surgery with a median follow-up time of 74.5 months. mRNA-BRCA1 level was assessed in frozen tumor specimens by real-time RT-PCR, whereas ER, HER2, CK5/6, CK17 and cyclin E expression in paraffin embedded specimens by immunohistochemistry. Results: Mean mRNA-BRCA1 level was 0.059 (median 0.014; range 0.000-1.928). Five-year survival rate of 58 patients with high expression of BRCA1 (≥median) was 87.4% (95% CI 75.4-93.8%) whereas in a group of 58 patients with low expression (<median) it was only 59.6% (45.7-71.0%) (log-rank p=.001). Low BRCA1 expression was an independent predictor of death, HR=3.38 (95%CI 1.42-8.07; p=.006). mRNA-BRCA1 level was significantly (p<.001) lower in 56 ER-negative patients when compared with 60 ER-positive ones, similar difference in transcript level was also observed between 23 HER2-positive and 93 HER2-negative patients (p=.003), 42 CK5/6-positive and 74 CK5/6-negative (p=.001), 29 CK17-positive and 87 CK17-negative (p=.004), 68 cyclin E-positive and 44 cyclin E-negative (p=.001) patients (in 4 cases assessment of cyclin E expression was not possible due to technical reasons), and between 52 patients with high grade (G3) and 64 patients with low grade (G1-2) tumors (p=.032). There was no correlation between mRNA-BRCA1 and age, tumor size and lymph node involvement. Conclusions: Assessment of mRNA-BRCA1 level may be of value in selecting breast cancer patients with more aggressive tumors and worse outcome and should be evaluated in a prospective manner. No significant financial relationships to disclose.
Group visits for women at high risk for breast cancer: Facilitated education and support sessions.
Authors: Kathryn Trotter, Victoria Seewaldt, Stephanie Riley
Journal: Journal of Clinical Oncology (2015)

30 Background: Women at increased risk for breast cancer frequently have anxiety and stress. They often have questions and concerns that are not discussed at their medical appointment. Methods: The Duke High-Risk Breast Clinic consists of over 1,110 women undergoing high-risk screening due to 1) BRCA-mutation, 2) familial pattern of breast cancer inheritance, 3) prior abnormal biopsy, or 4) &gt; 20% lifetime risk of breast cancer. Approximately 31% of clinic participants are African-American and 65% are European-American. Women participating in the Duke High-Risk Breast Clinic were offered a monthly, hour-long education and support session at no charge. The goal was to help women answer key questions and provide a supportive environment. A five-month pilot was initiated in 02/2015. The NP adapted the Centering Healthcare Institute’s group visit model (www.centeringhealthcare.org). Attendees completed a Self-Assessment Sheet (SAS) on arrival. A clinic conference room was used, with chairs arranged in a circle, and refreshments available. After an icebreaker opening, the NP led a facilitated discussion on timely topics, which the patients actively prioritized. Guest experts (radiologist, geneticist, gynecologist, mental health provider) also participated. A participant or the team navigator led the closing activity, and then a brief patient satisfaction survey was completed. Patient support persons were welcomed. Results: 100% of the participants (N = 38) strongly agreed that the educational session was a resourceful way of addressing healthcare concerns, and 92% agreed that they would attend more educational sessions. Several women came at least 3 of the sessions with 30% traveling 1-3 hours. Comments were positive. Common topics on the SAS were: genetic risk/testing, risk factors for breast cancer, screening tests/tools, and nutrition. Further topics requested: “When to be concerned about aches, pains, ‘lumps’, and how not to over react”, research updates, 3D imaging, and stress. Conclusions: Women found this group visit model highly informative and helpful. Several commented they would like the sessions to be longer, or be offered in the evening. Further commitment to this group visit format is warranted.
t(12;21)/TEL-AML1 confers a specific pattern of in vivo sensitivity to treatments in childhood B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL)
Authors: Caroline Piette, Stefan Suciu, Emmanuelle Clappier, Yves Bertrand, Geneviève Plat, Christophe Chantrain, Vitor Costa, Nicole Dastugue, Alina Ferster, Caroline Gilotay, Sandrine Girard, Nathalie Grardel, Patrick Lutz, Françoise Mazingue, Odile Minches, Martine Munzer, Emmanuel Plouvier, Nicolas Sirvent, Anne Uyttebroeck, Nadine van Roy, Karima Yakouben, Yves Benoit, Hélène Cavé
Journal: Blood (2015)
Screening of Mutations in BCR-ABL Kinase Domain in Chronic Myeloid Leukemia (CML) Patients Treated with Kinase Inhibitors by Denaturing High-Performance Liquid Chromatography (D-HPLC).
Authors: Cintia C. Mascarenhas, Anderson F. Cunha, Katia B.B. Pagnano, Rosana A. Silveira, Fernando F. Costa, Ricardo Pasquini, Nelma C.D. Clementino, Carmino A. De Souza
Journal: Blood (2007)
Neoadjuvant or adjuvant chemoradiation therapy for stage II-III esophageal squamous cell carcinoma.
Authors: Yongshun Chen, Daxuan Hao, Xiaoyuan Wu, Yuanyuan Yang, Chunyu He, Wen Wang, Jinsong Liu, Jianhua Wang
Journal: Journal of Clinical Oncology (2015)

202 Background: Esophageal cancer is the eighth most common cancer worldwide, and especially in China is the fourth most common cause of death. Clinical trials have explored the value of neoadjuvant or adjuvant chemoradiation in potentially resectable esophageal squamous cell carcinoma (ESCC); however, these studies have produced conflicting results. This retrospective study was performed to investigate whether patients with resectable stage II/III ESCC should receive neoadjuvant or adjuvant therapy in addition to surgery. Methods: A review of stage II/III ESCC patients who underwent esophagectomy and either neoadjuvant or adjuvant chemoradiation was performed. Patients who underwent neoadjuvant therapy were treated with one cycle of chemotherapy consisted of cisplatin and fluorouracil concurrently with radiotherapy (40Gy/20f), adjuvant therapy consisted of two cycles of chemotherapy concurrently with radiotherapy (46-50Gy/23-25f, 5 days/week). Results: A total of 122 patients met inclusion criteria, of which 49 underwent neoadjuvant chemoradiation and 73 underwent adjuvant chemoradiation. Median follow up was 36.5 months. The median survival times and 3, 5-year OS rates for the neoadjuvant and adjuvant groups were 39.3 vs 31.5 months, and 53.0%, 45.7% vs 42.9%, 29.7% respectively (p = 0.091). For the patients with stage III ESCC, the median survival times and 5-year OS rates for the neoadjuvant and adjuvant group were 39.3 vs 21.2 months, and 43.4% vs 15.4% respectively (p = 0.005). Among lymph node-positive patients, the median survival times and 5-year OS rates for the neoadjuvant and adjuvant groups were 55.6 vs 23.7 months, and 43.0% vs 25.7% respectively (p = 0.085). The incidence of postoperative complications was 26.5% (13/49) in the neoadjuvant group and 20.5% (15/73) in the adjuvant group (p = 0.212). Conclusions: Neoadjuvant chemoradiation does not increase postoperative complications, and is associated with better OS when compared to adjuvant chemoradiation. OS in stage III patients is significantly improved with the use of neoadjuvant chemoradiation.
Phase II study of vorinostat (Suberoylanilide Hydroxamic Acid, SAHA) in patients with advanced transitional cell urothelial cancer (TCC) after platinum-based therapy—California Cancer Consortium/University of Pittsburgh NCI/CTEP-sponsored trial
Authors: E. M. Cheung, D. I. Quinn, D. D. Tsao-Wei, S. G. Groshen, A. M. Aparicio, P. Twardowski, G. S. Chatta, P. N. Lara, D. R. Gandara
Journal: Journal of Clinical Oncology (2008)

16058 Background: There is no defined standard second-line therapy for patients (pts) with advanced TCC. Histone deacetylase inhibitors (HDACi) have anti-cancer activity in a variety of models including the modulation of apoptosis in bladder cancer cell lines (Earel JK Cancer Res 2006). The HDACi SAHA has recently been approved by the FDA for cutaneous T-cell lymphoma (Olson EA J Clin Oncol 2007). We evaluated the efficacy and toxicity of SAHA in patients with recurrent/metastatic TCC failing first line platinum-based therapy either in the adjuvant/neoadjuvant setting or for recurrent/advanced disease. Methods: SAHA was given orally 200 mg BID continuously until progression or unacceptable toxicity. Cycle length was 3 weeks. Primary end point was RECIST response rate (RR); a RR > 20% was deemed interesting in a 2-stage design requiring at least one response in the first 12 pts to proceed to the 2nd stage of 37 pts. Patients were imaged every 6 weeks. Results: Fourteen pts were entered. Patient characteristics: median age-65 years (43–84); Caucasian (93%); males (86%). Karnofsky performance status (> 90, <80) - 57%, 41%. Best responses: stable (3 pts), progression (8), death from other cause (1), & too early (2). Median number of cycles was 2 (range 1–11). Median disease free survival and overall survival times were 1.1 (1.0–2.1) & 4.3 (2.1–8.3) months, respectively. Toxicities were predominantly due to cytopenia and thrombocytopenic bleeding. Two early on-study deaths occurred. Five pts had grade 4/5 toxicity; 4 had grade 3. Two pts with stable disease had low grade (<2) toxicity and remained on therapy for 5+ months. The study closed to further accrual after review of first stage results. Conclusions: Suberoylanilide Hydroxamic Acid (vorinostat) in this dose-schedule proved surprisingly toxic and had limited efficacy in pts with advanced TCC. Further evaluation of lower dose regimens in combination with cytotoxic or target specific agents may be warranted but should be undertaken with caution. No significant financial relationships to disclose.
Rituximab, Fludarabine and Alkylating Agents in Peripheral Neuropathies Related to IgM Monoclonal Gammopathy with Autoantibody Activity against Myelin-Associated-Glycoprotein : a Retrospective Study of 15 Patients.
Authors: Lionel Karlin, Bertrand Arnulf, Lionel Galicier, Bouchra Asli, Marion Malphettes, Claire Fieschi, Sophie Cereja, Eric Oksenhendler, Jean-Paul Fermand, Jean-Claude Brouet
Journal: Blood (2009)
Comprehensive volume hyperfractionated (HFx) re-irradiation (Re-RT) of recurrent head and neck (H/N) cancer is feasible.
Authors: P. Kumar, U. K. Sinha
Journal: Journal of Clinical Oncology (2011)

5551 Background: A retrospective review of patients with recurrent head and neck (H/N) cancer treated with comprehensive volume re-irradiation (Re-RT) was conducted. Methods: Between 2003 and 2009, 23 patients underwent Re-RT for recurrent H/N cancer. Sites included the larynx (n=4), oropharynx (n=5), oral cavity (n=8), and other (n=5) non-nasopharynx sites. Unlike other published reports of head and neck Re-RT, patients Re-RT at USC received comprehensive volume (primary site of recurrence, involved nodal disease and bilateral draining nodal regions) hyperfractionated (HFx) RT (at 110-120 cGy/fx BID with at least a 6 hour interval to total planned dose of 7,680-7,700 cGy) with no planned treatment breaks. 17% of the patients were treated palliatively. The median dose of previous RT was 6680 cGy (range 5,040-7,200cGy), and the median interval from the initial RT was 17 months (6-228 mos). Only two patients received concurrent chemotherapy [cisplatin (n=1), erbitux (n=1)]. Results: The median Re-RT dose was 7320cGy (3240cGy – 7700 cGy). The median duration of treatment was 49 days, and the median number of break days was 6 (0-26 d). Ten (43%) of the 23 patients completed their planned HFx Re-RT without any treatment related breaks. 18 patients required a treatment related break of 1 week or less, while 5 patients needed a treatment related break of more than 1 week due to PEG placement (n=3), infection (n=1) and mucositis (n=1). Major acute toxicities consisted of grade 3 mucositis in 17% of patients and grade 3 skin desquamation in 22%. No patients were lost to follow up. The median overall survival after Re-RT was 3 months (range 0-26 months). One patient is alive and cNED at 26 months. Another patient died cNED at 26 months from a non-cancer related cause. Eight patients died secondary to metastatic disease and 4 more patients chose hospice after completing palliative Re-RT. Only 4 patients treated curatively experienced documented local failure. Conclusions: Comprehensive volume HFx Re-RT with no planned treatment breaks is feasible and tolerable. Based upon our institutional experience, we plan to initiate a phase I/II trial testing comprehensive volume Re-RT in patients with recurrent H/N cancer.
Expression of E-Cadherin and uPA and its association with the prognosis for pancreatic cancer
Authors: K. H. Lee, S. J. Shin, M. K. Kim, M. S. Hyun, J. Choi, H. S. Song, S. H. Bae
Journal: Journal of Clinical Oncology (2005)

4200 Background: The expression of E-Cadherin(ECD) and Urokinase Plasminogen activator(uPA) has been noted as makers for tumor metastasis and prognosis in several tumors, so we investigated the relationship between the expression of ECD, uPA and the clinicopathologic characteristics. Methods: The expression of E-cadherin and uPA was evaluated immunohistologically using monoclonal antibodies in paraffin-embedded pancreatic cancer tissues from 53 patients. Results: Among 53 tumor tissues, tumor tissues from 29 (54.7%) patients showed positive E-cadherin expression. 22 (41.5%) patients showed positive expression with uPA. There were four subgroups of the E-cadherin and uPA expression: E-cadherin-positive/uPA-negative, E-cadherin-negative/uPA-negative, E-cadherin-positive/uPA-positive, and E-cadherin-negative/uPA-positive. These patterns were found in 14 (26.4%), 11 (20.8%), 9 (17%), and 19 (35.8%) of the 53 tumor tissues, respectively. According to the subgroup pattern of E-cadherin and uPA expression, the tumor tissues with E-cadherin-negative and uPA-positive expression were associated with larger tumor, distant metastasis and an increased clinical stage. Patients with E-cadherin-negative pancreatic tissue had a shorter survival (10.6 months; 95% CI 8.7–12.5 months) than the patients in whom the expression of E-cadherin was positive (median 15 months; 95% CI 12.3–17.6 months, P > 0.05). Patients with uPA-positive pancreatic tissue had a shorter survival (6.4 months; 95% CI 1.8–11 months) than did the patients having pancreatic tissue with uPA-negative expression (median 18.7 months; 95% CI 5.3–32 months, P < 0.01). There was a difference for the median survival time between the patients with uPA-negative/E-cadherin-positive pancreatic tissue (median 18.7 months; 95% CI 0.56 - 36.8 months) and the patients with uPA-positive/E-cadherin-negative pancreatic tissue (median 7.5 months; 95% CI 4.5–10.5 months, P < 0.05), and there was a statistically significant difference in survival curves between these two groups. Conclusions: The combined analysis concerning uPA and E-cadherin expression may be a useful predictor of metastasis. No significant financial relationships to disclose.