tbuckley/cabot-search huggingface dataset:
Significantly different costs of adjuvant chemotherapy regimens in the United States.
Authors: R. G. Chellappah, P. Ravdin
Journal: Journal of Clinical Oncology (2011)

1131 Background: We examined the relative and absolute costs in the United States for several widely used breast cancer adjuvant chemotherapy regimens. Although clinical trials commonly report the endpoints of efficacy (in terms of relapse free survival and overall survival) and toxicity, clinical trials rarely comment on the costs of the therapy. There are several reasons for this. One is that the costs are time and site and/or country specific. It is noteworthy that the total cost ideally includes the cost for care and may not be easily captured from the clinic (additional laboratory tests, radiology, hospitalization, etc.). Nonetheless simple cost estimate based on costs in the clinic can be so strikingly different, that they would seem to worth taking into consideration and examining further. Methods: To make the estimates we used the Regimen Profiler available at https://www.onmarkservices.com. We used Medicare reimbursement cost estimates effective in January 2011. The cost estimates were based treatment of a 70 kg woman with a BSA of 1.6 m2. Results: An example of these analyses are cost estimates for the chemotherapy alone which for dose dense CA (Q2w)*4 followed by P (q2w)*4, CA (q3w)*4 followed by P (qw)*12, DAC (q3w)*6, and 4*DC (q3w)*4 were: $924, $1,024, $14,827, and $9,890 respectively. For the dose dense regimen and the DAC regimen growth factor support is recommended. If the cost of support with a long acting form of CSF is included the costs become $21,274, $4,140, $31,222, and $10,651. Conclusions: We found that estimates of the cost of adjuvant chemotherapy regimens varied widely. The inclusion of a non-generic agent, or the necessity of routine growth factor support greatly increase the cost. By far the least costly of the third generation adjuvant breast cancer regimens was CA*4 then P*12, the efficacy and safety of which was established in E1199. The DC regimen cost comparatively little but, estimates of its efficacy and safety are based on only one trial against a relatively simple regimen. We conclude the cost differentials between widely used breast cancer regimens for adjuvant therapy are so large that particularly when efficacy and safety are approximately equal, that cost should be estimated and taken into consideration.
Retroperitoneal sarcomas: 20 years experience at a tertiary Asian center.
Authors: S. Y. Lee, M. Teo, R. H. H. Quek, B. K. P. Goh, W. Chen, A. Y. F. Chung, H. N. Koong, W. K. Wong, L. L. Ooi, K. C. Soo
Journal: Journal of Clinical Oncology (2011)

e20522 Background: Soft tissue sarcomas are rare and account for less than 1% of all newly diagnosed malignancies. Approximately 15% of soft tissue sarcomas arise in the retroperitoneum and they present complex clinical problems where surgery forms the mainstay of treatment. Previous studies have shown that high histologic grade and incomplete gross resection are the most important prognostic factors for survival. The study was conducted to evaluate the clinical results of an aggressive resection policy for retroperitoneal sarcomas in an Asian centre and to determine the prognostic factors for disease recurrence and patient survival. Methods: A prospective database was used to identify 112 patients with primary or recurrent retroperitoneal sarcoma treated between July 1990 and December 2009. Histology at primary presentation was reviewed and subtyped according to WHO classification. The influence of clinicopathological factors on disease free interval and overall survival was analysed using a multivariate model. Results: One hundred and twelve patients with primary or recurrent retroperitoneal sarcoma operated on for curative intent (48 Males, 64 Females; mean age 51.4 years old) were evaluated. The median tumor size was 13 cm (range: 5–43 cm). Median follow-up time was 74.8 months. Surgical margins were involved in 27.7% of patients. Resection of contiguous organs was required in 56.3% of patients to achieve gross surgical margins. Median disease-free survival at 3- and 5-, 7-, 10-year was 38%, 23.7%. 21.1% and 12.7% and overall survival rate at 3- and 5-, 7-, 10-year was 79.3%, 64.6%, 45.3% and 34% respectively. Surgical margins involvement was identified by multivariate analysis to be significantly associated with worse survival. Sarcomas in Stage II, or are high grade are significantly associated with poorer disease-free survival. Conclusions: An aggressive surgical approach in both primary and recurrent retroperitoneal sarcomas is associated with long-term survival. Local control continues to be a significant problem in the management of retroperitoneal sarcomas requiring contiguous organ resection in majority of the patients. Poor prognosis is associated with involved surgical margins, higher stage and grade of tumour.
Can we predict malignancy in Bosniak III renal lesions identified on multiphasic CT scan?
Authors: Joseph C. Klink, Ajit H. Goenka, Erick M. Remer, Andrew D. Smith, Nancy A. Obuchowski, Steven C. Campbell
Journal: Journal of Clinical Oncology (2012)

381 Background: To identify independent predictors of malignancy in Bosniak III (BIII) renal lesions and to build a prediction model based only on readily identifiable clinical and imaging variables. Methods: In this IRB-approved retrospective study, radiology and hospital information systems were interrogated for BIII lesions in CT reports from January 1, 1994 to August 31, 2009. Patients with histopathology available were included. The following variables were recorded: age, gender, body mass index (BMI), race, symptoms at presentation, smoking history and history of renal cell carcinoma (RCC), presence of a co-existent BIII or BIV lesion. Univariate analyses were first performed using logistic regression analysis with generalized estimating equations and an exchangeable working correlation matrix to test each variable. Factors with univariate p-values &lt;0.20 were considered in the multiple-variable analysis. The main effects of the factors were first evaluated. For the main effects with p-values &lt;0.10, two-way interactions were assessed. Interactions with p-values &lt;0.05 were included in the final model along with their main effects. The c-index was used to test accuracy of the models. Final model was chosen based on its parsimony and accuracy. Results: Mean patient age was 58 years (range 27–80). There were 51 females and 50 males. Of the 107 BIII lesions in 101 patients (6 patients had two lesions each), 59 (55%) were malignant and 48 (45%) were benign. The strongest predictors of malignancy were race (p=0.04), history of RCC (p=0.03), co-existing III (p=0.03) or IV lesion (p=0.10) and BMI (p=0.10). In multiple-variable analysis, a history of RCC was the strongest independent predictor of malignancy (OR 12.7, 95% CI 1.8– 91, p=0.01) followed by BMI (OR 1.1, 95% CI 0.99–1.20, p=0.08). No other main effects or interactions had p-values &lt;0.10. The model with these two predictors had an accuracy of 0.68. At &gt;90% probability of malignancy, the model has a 77% sensitivity and 61% positive predictive value. Conclusions: Clinical and imaging variables provide significant ability to predict malignancy for BIII renal lesions. A model encompassing history of RCC and BMI appears promising but merits refinement on an independent dataset.
Bacterial Interactions with Immobilized Liquid Layers
Authors: Yevgen Kovalenko, Irini Sotiri, Jaakko V. I. Timonen, Jonathan C. Overton, Gareth Holmes, Joanna Aizenberg, Caitlin Howell
Journal: Advanced Healthcare Materials (2016)

Bacterial interactions with surfaces are at the heart of many infection-related problems in healthcare. In this work, the interactions of clinically relevant bacteria with immobilized liquid (IL) layers on oil-infused polymers are investigated. Although oil-infused polymers reduce bacterial adhesion in all cases, complex interactions of the bacteria and liquid layer under orbital flow conditions are uncovered. The number of adherent Escherichia coli cells over multiple removal cycles increases in flow compared to static growth conditions, likely due to a disruption of the liquid layer continuity. Surprisingly, however, biofilm formation appears to remain low regardless of growth conditions. No incorporation of the bacteria into the layer is observed. Bacterial type is also found to affect the number of adherent cells, with more E. coli remaining attached under dynamic orbital flow than Staphylococcus aureus, Pseudomonas aeruginosa under identical conditions. Tests with mutant E. coli lacking flagella confirm that flagella play an important role in adhesion to these surfaces. The results presented here shed new light on the interaction of bacteria with IL layers, highlighting the fundamental differences between oil-infused and traditional solid interfaces, as well as providing important information for their eventual translation into materials that reduce bacterial adhesion in medical applications.
A Phase II Clinical Study of Rituximab and High-Dose Biweekly THP-COP (Pirarubicin, Cyclophosphamide, Vincristine and Predonisolone) with G-CSF for Non-Hodgkin Lymphoma: Results of a Multicentric Study of NMLSG (Niigata Malignant Lymphoma Study Group).
Authors: Jun Takizawa, Sadao Aoki, Kazue Takai, Tohri Kurasaki, Keiichiro Honma, Masutaka Higashimura, Kouichi Nagai, Akihito Momoi, Koji Nikkuni, Yoshufusa Aizawa
Journal: Blood (2005)
The potential economic impact of the 21-gene recurrence score: Guided chemotherapy in a population-based cohort with node-negative and node-positive early-stage breast cancer.
Authors: N. W. D. Lamond, C. Skedgel, D. Rayson, L. Lethbridge, T. Younis
Journal: Journal of Clinical Oncology (2011)

201 Background: The 21-gene recurrence score (Oncotype DX: RS) appears to augment clinical-pathological prognostication and predicts adjuvant chemotherapy (chemo) benefits in patients with node-negative (N-) and node-positive (N+) hormone-receptor positive early-stage breast cancer. Economic analyses suggest that RS-guided chemo is a cost-effective strategy in N- breast cancer, but no evaluations were reported for N+ disease based on pre RS chemo utilization in clinical practice. We examined the cost-utility (CU) of a RS-guided chemo strategy, compared to current practice without RS in a population based cohort, in N- and N+ early-stage breast cancer. Methods: A generic state-transition model was developed to compute cumulative costs and quality-adjusted life years (QALY) over a 25-year horizon for patients with hormone-receptor positive early-stage breast cancer considered for chemo. We examined outcomes with and without chemo in RS-untested cohorts and in those with low, intermediate and high RS based on the reported prognostic and predictive impact of the RS. Chemo utilizations (current vs RS-guided), costs and utilities were derived from a Nova Scotia population based cohort, local resources and the literature. Sensitivity analyses were conducted for key model assumptions/parameters. Results: RS-guided chemo strategy is associated with incremental costs and QALY gains compared to chemo with no RS testing in both N- and N+ patients. The resultant CU ratios are $17,141/QALY and $5,772/QALY for N- and N+ disease, respectively. These CU ratios are well below commonly quoted thresholds and were most sensitive to RS-distribution, upfront chemo costs, chemo utilization rates and relative benefits of chemo in various RS-strata. Conclusions: RS-guided chemo in a population based cohort appears to be a cost-effective strategy, compared to chemo with no RS testing, in N- and N+ early-stage breast cancer.
Polyclonal Free Light Chain Elevation and Mortality In the German Heinz Nixdorf Recall Study
Authors: Lewin Eisele, Jan Dürig, Andreas Huttmann, Ulrich Dührsen, Anja Führer, Sabrina Kieruzel, Martina Bröcker-Preuss, Beate Bokhof, Raimund Erbel, Klaus Mann, Karl-Heinz Jöckel, Susanne Moebus
Journal: Blood (2010)
Predicting MEK Inhibitor Response in Lung Cancer: A Proper Signature Is Required
Authors: Yaohua Xue, Piro Lito
Journal: Clinical Cancer Research (2016)

Abstract The ERK signaling pathway is one of the most commonly deregulated pathways in cancer. Assays that accurately measure ERK signaling output in clinical specimens would be extremely helpful not only in determining the pharmacodynamic effects of drug treatment but also in selecting those patients most likely to respond to therapy. Clin Cancer Res; 23(6); 1365–7. ©2016 AACR. See related article by Brant et al., p. 1471
Micafungin Versus Voriconazole for Empirical Antifungal Therapy In Febrile Neutropenic Patients with Acute Myeloid Leukemia: A Randomized, Controlled Trial.
Authors: Tatsuo Oyake, Shugo Kowata, Kazunori Murai, Shigeki Ito, Tomoaki Akagi, Koumei Kubo, Kenichi Sawada, Yoji Ishida
Journal: Blood (2010)
Should We Screen for Vitamin D Deficiency?
Authors: Howard Libman, Alan O. Malabanan, Gordon J. Strewler, Eileen E. Reynolds
Journal: Annals of Internal Medicine (2016)

The U.S. Preventive Services Task Force (USPSTF) recently issued guidelines on screening for vitamin D deficiency. The guidelines were based on randomized trials of vitamin D deficiency screening and treatment, as well as on case–control studies nested within the Women's Health Initiative. The USPSTF concluded that current evidence is insufficient to assess the benefits and harms of screening for vitamin D deficiency in asymptomatic adults. Compared with placebo or no treatment, vitamin D was associated with decreased mortality; however, benefits were no longer seen after trials of institutionalized persons were excluded. Vitamin D treatment was associated with a possible decreased risk for at least 1 fall and the total number of falls per person but not for fractures. None of the studies examined the effects of vitamin D screening versus not screening on clinical outcomes. In this Grand Rounds, 2 prominent endocrinologists debate the issue of screening for vitamin D deficiency in a 55-year-old, asymptomatic, postmenopausal woman. They review the data on which the USPSTF recommendations are based and discuss the potential benefits and risks, as well as the challenges and controversies, of screening for vitamin D deficiency in primary care practice.
Phase II study of gemcitabine (G) and bevacizumab (B) as first-line treatment in taxane-pretreated, HER2-negative, locally recurrent or metastatic breast cancer (MBC).
Authors: R. Borson, W. G. Harker, J. E. Reeves, D. Drosick, J. T. Beck, S. J. Hager, W. L. Horvath, J. Bromund, H. Zeigler, D. Tai, D. A. Yardley
Journal: Journal of Clinical Oncology (2011)

1052 Background: Bevacizumab with chemotherapy has shown improvement in progression-free survival (PFS) in MBC patients (pts) (Miller 2007; Miles 2008; Brufsky 2009; Robert, et al 2009). We examined the efficacy/safety of combining B with G as first-line therapy in taxane-pretreated MBC pts. Methods: This US, multicenter, single arm, open-label trial enrolled 52 pts. Eligibility criteria included: HER2-negative, recurrent or MBC, performance status (PS) 0-1, and prior taxane as neoadjuvant and/or adjuvant therapy with a >12 month disease-free interval. Pts received G 2500 mg/m2 plus B 10 mg/kg on day (d) 1, both in 14−d cycles. Pts were treated until progressive disease (PD), complete response (CR), or intolerable toxicity. The primary endpoint was PFS; secondary endpoints were overall response rate (ORR), 1−year survival rate, and safety. Toxicities were graded according to NCI CTC v 3.0. Results: Between March 2008 and January 2010, 52 women were enrolled and treated. Median age 55 (range 28−78); 30 ER+/PR+; 19 ER-/PR-/HER2-; PS 0/1, 28/24 pts. Five pts experienced ≥1 serious drug-related adverse event (AE). Ten pts discontinued due to AEs; 5 pts were hospitalized for drug-related AEs. Drug-related treatment-emergent AEs (TEAEs) of all grades present in >20% of pts were: nausea (51.9%), fatigue (46.2%), anorexia (21.2%), neutropenia (23.1%), and anemia (21.2%). Grade (Gr) 3 drug-related TEAEs occurring in ≥2% of pts were neutropenia (13.5%), leukopenia (7.7%), hypertension (7.7%), thrombocytopenia (3.8%), and anemia (3.8%). Two pts experienced Gr 4 TEAEs: 1 pt, hemolytic uremic syndrome + acute renal failure + leukopenia; 1 pt, pulmonary embolism. There were no deaths from study drug toxicity. The median number of cycles received was 8 (range 1−30). Median dose intensities were: G, 96.8% and B, 97.6%. The ORR was 21.4% (0 CR; 9 partial responses). Nineteen (45.2%) pts had stable disease. Median PFS is 4.8 months (95% confidence interval: 3.4−7.2). The 1−year overall survival rate is 67.1%. Conclusions: Therapy with G+B is well tolerated with demonstrated activity in this poor prognosis group. Final efficacy data will be presented at the meeting.
Cord Colitis: An Antibiotic-Responsive Colitis Syndrome Following Cord Blood Stem Cell Transplantation
Authors: Gabriela Soriano, Alex F Herrera, Jason L Hornick, Erin Gilmore, Vincent T Ho, Karen K Ballen, Lindsey R Baden, Corey S Cutler, Joseph H. Antin, Robert J Soiffer, Francisco M Marty
Journal: Blood (2010)
Invasive pneumococcal disease in children aged younger than 5 years in India: a surveillance study
Authors: Anand Manoharan, Vikas Manchanda, Sundaram Balasubramanian, Sanjay Lalwani, Meera Modak, Sushama Bai, Ajith Vijayan, Anita Shet, Savitha Nagaraj, Sunil Karande, Gita Nataraj, Vijay N Yewale, Shrikrishna A Joshi, Ranganathan N Iyer, Mathuram Santosham, Geoffrey D Kahn, Maria Deloria Knoll
Journal: The Lancet Infectious Diseases (2016)
Extreme genomic erosion after recurrent demographic bottlenecks in the highly endangered Iberian lynx
Authors: Federico Abascal, André Corvelo, Fernando Cruz, José L. Villanueva-Cañas, Anna Vlasova, Marina Marcet-Houben, Begoña Martínez-Cruz, Jade Yu Cheng, Pablo Prieto, Víctor Quesada, Javier Quilez, Gang Li, Francisca García, Miriam Rubio-Camarillo, Leonor Frias, Paolo Ribeca, Salvador Capella-Gutiérrez, José M. Rodríguez, Francisco Câmara, Ernesto Lowy, Luca Cozzuto, Ionas Erb, Michael L. Tress, Jose L. Rodriguez-Ales, Jorge Ruiz-Orera, Ferran Reverter, Mireia Casas-Marce, Laura Soriano, Javier R. Arango, Sophia Derdak, Beatriz Galán, Julie Blanc, Marta Gut, Belen Lorente-Galdos, Marta Andrés-Nieto, Carlos López-Otín, Alfonso Valencia, Ivo Gut, José L. García, Roderic Guigó, William J. Murphy, Aurora Ruiz-Herrera, Tomas Marques-Bonet, Guglielmo Roma, Cedric Notredame, Thomas Mailund, M. Mar Albà, Toni Gabaldón, Tyler Alioto, José A. Godoy
Journal: Genome biology (2016)

Genomic studies of endangered species provide insights into their evolution and demographic history, reveal patterns of genomic erosion that might limit their viability, and offer tools for their effective conservation. The Iberian lynx (Lynx pardinus) is the most endangered felid and a unique example of a species on the brink of extinction.
Srsf2 P95H Mutation Causes Impaired Stem Cell Repopulation and Hematopoietic Differentiation in Mice
Authors: Ayana Kon, Satoshi Yamazaki, Yasunori Ota, Keisuke Kataoka, Yusuke Shiozawa, Maiko Morita, Tetsuichi Yoshizato, Masashi Sanada, Kenichi Yoshida, Manabu Nakayama, Haruhiko Koseki, Hiromitsu Nakauchi, Seishi Ogawa
Journal: Blood (2015)
Update of the HIPRO study: Late toxicity and outcome at seven years.
Authors: D. Thomson, S. Merrick, R. Swindell, J. Coote, P. A. Elliott, R. Cowan, J. Wylie, J. Logue, J. E. Livsey, A. Choudhury
Journal: Journal of Clinical Oncology (2011)

81 Background: Dose-escalated radiotherapy for localised prostate cancer improves disease control but at the expense of increased overall treatment time and late toxicity. Given the low alpha-beta ratio for prostate cancer, treatment with hypofractionation should be biologically advantageous. Intensity-modulated radiotherapy (IMRT) allows dose escalation with hypofractionation, while achieving acceptable levels of toxicity. We report our 7 year late toxicity data in patients treated with two such regimens within the Hypofractionated Dose Escalation utilising Intensity-modulated Radiotherapy in Carcinoma of the Prostate (HIPRO) study. Methods: Sixty men, median age 75 years (50-87), with localised adenocarcinoma of prostate (T1-3NOMO) and either Gleason score ≥7 or PSA 20-50ng/L received 57Gy in 19 fractions (n=30) or 60Gy in 20 fractions (n=30) using 5-field inverse-planned IMRT. All patients received neoadjuvant hormone therapy, continuing for up to 6 months after treatment. Late toxicity was assessed at 7 years follow-up using RTOG criteria and LENT/SOMA questionnaire. Results: Forty-four (73%) patients were alive at 7 years. Nine patients (21%) reported RTOG grade 1 bowel or bladder toxicity; there was no grade 2 toxicity or above and no difference between the fractionation schedules. LENT/SOMA questionnaires were returned by 31/44 patients. Mean and median scores were less than one for bowel and urinary symptoms. When compared with pre-treatment, the proportion of patients with significant (maximum LENT/SOMA ≥2) urinary symptoms remained similar (75% vs. 76%), problems with sexual function had decreased (84% vs. 98%) but bowel symptoms increased (62% vs. 25%). At 5 years, overall survival was 83% and 74% and cause-specific survival was 83% and 84% in the 57Gy and 60Gy groups respectively. Conclusions: Dose-escalated hypofractionated IMRT for prostate cancer appears well tolerated with acceptable levels of late toxicity. Studies to assess long term disease control with these regimens are on-going. No significant financial relationships to disclose.
Effect of estrogen receptor beta expression (ERße) in triple-negative breast cancer (TNBC) patients treated in the neoadjuvant GeparTrio trial.
Authors: F. Heitz, B. Sinn, S. Loibl, A. Du Bois, C. Jackisch, S. Kuemmel, C. Denkert, J. Barinoff, K. Mehta, G. Von Minckwitz
Journal: Journal of Clinical Oncology (2011)

1069 Background: TNBC is defined as tumor that lack expression of estrogen receptor (ER), progesterone receptor (PgR) and HER2. Pts with TNBC have a relatively poor prognosis but usually respond well to chemotherapy-the only systemic treatment option- but those who achieve a pathological complete response (pCR) have an excellent prognosis. Numerous efforts have been undertaken to further characterize this group. ER-α is assessed routinely in pathological work-up. Another subtype of ER, ER beta has been described, but conflicting results have been published. We investigated the impact of ERße in neoadjuvant treated TNBC pts. Methods: Tissue microarrays from core biopsies of 93 TNBC pts recruited to the phase III GeparTrio trial, receiving 6-8 cycles neoadjuvant TAC/NX chemotherapy, were centrally stained immunohistochemically for ER-α, ER-beta (clone 14C8), PgR and HER2. ERße was assessed using the immunoreactive score: low (IRS: 0-4) or high (IRS>4). Pts received no neoadjuvant tamoxifen. Results: Nuclear and cytoplasmic ERße was high in 54.8% and 5.4%, respectively, but neither cytoplasmic nor nuclear ERße was found to be correlated with tumor size, nodal status, grading or histology. Due to low cytoplasmic expression, further analyses were restricted to nuclear expression. pCR rate was 34% in the TNBC group with 27% in the ERße high and 40% in the ERße low group (p=0.2). After a median follow-up of 56 months, 23 pts (24.7%) had relapsed (14/93 pts (15.0%) with low and 9/93 (9.6%) with high ERße) and 14 pts (15.1%) have died (6/93 pts (6.5%) with low and 8/93 (8.6%) with high ERße). 5 year overall- and progression-free survival rates were not significantly different between patients with low and high nuclear ERße, 85.8 months vs 83.6 months (p=0.78) and 65.6 months vs 77.3 months, (p=0.12), respectively. Conclusions: An apparently high proportion of pts with TNBC showed high nuclear ERße. Impact of nuclear ERße on pCR rates and survival rates was not distinctive in TNBC pts, thus prognostic relevance of ERße seems to be minimal in TNBC at most. Tamoxifen might alter the prognosis of TNBC pts whose tumors express ER beta.