tbuckley/cabot-search huggingface dataset:
Novel methodology for cost evaluation of anticancer drugs in castrate-resistant prostate cancer.
Authors: Helmy M. Guirgis
Journal: Journal of Clinical Oncology (2013)

200 Background: There is a need for a screening methodology to evaluate cost effectiveness of anticancer drugs. High costs raise concerns on approval, affordability and utilization. Objectives: Develop simplified methodology to screen and score cost versus value survival of docetaxel, cabazitaxel, abiraterone and sipuleucel-T in castrate- resistant prostate cancer (CRPC) Methods: Estimated costs in US $ of the entire course of an evaluated drug were added to downstream ancillary costs. The total was divided by the reported median survival gain over control in days. A reference value scale between 0- 100% was constructed with 0% assigned to cost/overall survival (OS) &gt; $750, life threatening/ fatal adverse events (AEs) and worsened quality of life (QoL). A plan was designed to correct for AEs and QoL. Results were expressed as cost/OS and value and corrected scores. Results: Abiraterone at $5,000 per month x 6 months demonstrated cost/OS of $256 with 66% value and 61% corrected scores. Abiraterone x 9-12 months raised cost/OS and decreased scores. Generic docetaxel x 8 cycles demonstrated $63 cost/OS and 92% value score. Ancillary treatment increased cost/OS to $136 and decreased score to 82%. Cost/OS of cabazitaxel x 6 cycles ranged from $477- $596 with 21-36% scores. Corrections for AEs and QoL reduced scores to 6-21%. Sipuleucel-T demonstrated relatively higher cost/OS and lower scores. Conclusions: Preliminary findings would support utilization of docetaxel and abiraterone more than cabazitaxel and sipuleucel-T. The proposed methodology of cost versus value-survival could facilitate cost evaluation and budgetary planning of anticancer drugs.
T-Bird (thalidomide, clarithromycin/[Biaxin®], lenalidomide/[Revlimid®], Dexamethasone) Therapy in Newly Diagnosed Symptomatic Multiple Myeloma
Authors: Tomer M Mark, Manan Shah, Melissa Rodriguez, Ryann Quinn, Roger N Pearse, Faiza Zafar, Karen Pekle, Patrice Mignott, David Jayabalan, Scott A Ely, Morton Coleman, Selina Chen-Kiang, Ruben Niesvizky
Journal: Blood (2011)
Ex vivo prostate cancer explant organ culture model system for targeted drug development in prostate cancer
Authors: Shilpa Gupta, Lei Gu, Zhiyong Liao, Peter McCue, Edouard John Trabulsi, Marja T. Nevalainen
Journal: Journal of Clinical Oncology (2013)

110 Background: Effective drug development does not always occur successfully in prostate cancer despite discovery of pathways and targeted agents due to lack of pre-clinical models that effectively mimic prostate cancer in humans. We optimized a novel Ex vivo organ-culture model system using clinical human prostate cancers to test novel therapeutic agents targeting the Jak2/Stat5a/b pathway in prostate cancer; this pre-clinical model may be useful to test novel drugs in prostate cancer for target validation and efficacy. Methods: Organ explant cultures of prostate cancers from 16 patients undergoing radical prostatectomy were performed within 2 hours of surgery, 1-2 mm fresh tissue explants were cultured in a medium containing different doses of pharmacologic inhibitor of Stat5a/b (IST5-002) or a small molecule Jak2 inhibitor with appropriate controls and treated with the drug daily for 7 days. Explants were fixed and analyzed for viability by hematoxylin-eosin staining and “in situ DNA end-labeling” assays, Stat5 activation was analyzed by immunohistochemistry for phosphorylated Stat5a/b. Results: Morphology of prostate cancer was well maintained and dose-dependent tumor responsesoccurred with the Stat5a/b and Jak2 inhibitors. The minimum effective dose of each drug was 25 micromoles and considerable effects on morphology and apoptosis were seen at 50 micromoles. Conclusions: Inhibition of the /Stat5a/b pathway showed promising preclinical activity in prostate cancer as demonstrated by our 3D-ex vivo explant organ culture model system using clinical human prostate cancers, corroborating the data from prostate cancer cell lines and xenograft prostate tumors. This model system may also serve as an effective pre-clinical tool to explore new targets and analyze the effects of different targeted therapies in prostate cancer. Finally, since this uses Ex vivo prostate cancer explants from individual prostate cancer patients, once could test different targeted agents in parallel and based on the efficacy of individual drugs, select patients who would best respond to a particular drug, thus providing an effective personalized medicine approach.
Sixty seconds on . . . the full course
Authors: Nigel Hawkes
Journal: BMJ (2017)

Almost everybody says so. Listen to NHS Choices: “If you stop taking an antibiotic part way through a course, the bacteria can become resistant to the antibiotic.” So by stopping you’re contributing to the growing threat of antimicrobial resistance.

Hmm, I see I can’t fob you off so easily. A growing number of experts agree with …
Multimodality treatment of colorectal peritoneal metastasis with perioperative systemic chemotherapy, cytoreductive surgery (CRS), and HIPEC: First safety results of the COMBATAC trial.
Authors: Pompiliu Piso, Michael Koller, Dirk Arnold, Hans J. Schlitt, Gabriel Glockzin
Journal: Journal of Clinical Oncology (2014)

LBA382 Background: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) provide a promising therapeutic option as part of an interdisciplinary multimodal treatment regimen for selected patients with peritoneal metastasis arising from colorectal cancer. The COMBATAC trial evaluates the feasibility, safety, and efficacy of perioperative cetuximab-containing systemic polychemotherapy, CRS and bidirectional oxaliplatin-based HIPEC. Methods: The COMBATAC trial is a prospective, multicenter, open-label, single-arm, single-stage phase II trial recruiting patients with histologically proven wild-type KRAS colorectal or appendiceal adenocarcinoma and synchronous or metachronous peritoneal metastasis. The planned total number of patients to be recruited is 60. The primary endpoint is progression-free survival (PFS). Results: Preliminary data of the first 16 documented patients show a total number of 51 adverse events. According to CTCAE v4 the distribution of AE was 23 grade 1, 14 grade 2, 13 grade 3, and one grade 4, respectively. Of the 14 grade 3/4 adverse events three were chemotherapy-related, four surgery-related, and seven not directly treatment-related. Most common grade 3/4 complications were infection, thrombosis, and urinary tract obstruction. Conclusions: First data indicate that perioperative systemic polychemotherapy including cetuximab in combination with CRS and bidirectional HIPEC is feasible and might not lead to increased morbidity and toxicity rates. Nevertheless, the COMBATAC trial is still recruiting, and data regarding progression-free survival (PFS) and overall survival (OS) is not yet available. Clinical trial information: NCT01540344.
Outcomes of neoadjuvant chemotherapy with FOLFOX/FOLFIRINOX and chemoradiotherapy in borderline resectable pancreatic cancer: Single-institution experience.
Authors: Chang O Son, Sachin Gopalkrishn Pai, Suma Satti, Adriana Dornelles, John S. Bolton, W. Charles Conway, Jyotsna Fuloria
Journal: Journal of Clinical Oncology (2014)

327 Background: The clinical benefit of neoadjuvant treatment in locally advanced pancreatic adenocarcinoma (borderline/unresectable) has not been well established. However, the challenge of managing locally advanced pancreatic adenocarcinoma has led to the incorporation of neoadjuvant treatment into clinical practice. FOLFIRINOX has been increasingly used as neoadjuvant chemotherapy, but may not be well tolerated especially in older patients due to adverse effect profile. In our institution, we have used FOLFOX as an alternative for older patients and patients with poor performance status based on our retrospective observation of FOLFOX in metastatic/advanced pancreatic adenocarcinoma. Methods: We conducted a retrospective analysis of locally advanced pancreatic cancer patients from January 1, 2011 to February 28, 2013 treated with neoadjuvant chemotherapy (FOLFOX/FOLFIRINOX) with the intention of future resection. In addition patients also received neoadjuvant chemo-radiotherapy. Imaging studies, operative notes and Pathology reports were reviewed. Results: 27 patients were analyzed, 10 received FOLFIRINOX and 17 received FOLFOX regimen. Mean age of patients were 57.28 ± 11.68 SD and 68.66± 11.21 SD in the two groups respectively. Patients received 4.2 ± 0.92 SD and 3.59 ±1.06 SD cycles of chemotherapy in FOLFIRINOX and FOLFOX groups respectively. Mean duration of follow up was similar in both groups. 5 patients on FOLFOX and 1 patient on FOLFIRINOX had disease progression thereby precluding surgery. The Rate of R0 resections was 64.7 % and 60% (P 0.27) in the two groups respectively. Overall survival was not statistically significant between the two groups. (Kaplan Meier survival graphs will accompany final presentation). Conclusions: In our study, FOLFIRINOX was administered in younger patients. However the R0 resection rates were similar in both the groups. FOLFOX may be acceptable neoadjuvant chemotherapy of choice in patients with borderline functional status. Randomized trials are needed to define this better.
Expression level of lipoprotein lipase in patients with chronic lymphocytic leukemia and its correlation with other prognostic factors
Authors: W. Xu, J. Li, Q. Shen, Y. Wu, H. YU, L. Fan
Journal: Journal of Clinical Oncology (2008)

18000 Background: Chronic lymphocytic leukemia (CLL) is the most common adult form of leukemia in the Western world, however, infrequent in the Eastern. It shows a remarkable heterogeneity, with some patients having an almost normal lifespan, others surviving only several years after diagnosis despite intensive therapy. A series of recent microarray studies have identified a number of other potential prognostic factors that have not yet been validated for their clinical importance. One of the genes most closely related to IgVH mutational status is lipoprotein lipase (LPL). Methods: To investigate LPL expression level in Chinese patients with CLL and its correlation with other prognostic factors, including IgVH mutation status, Binet stages, ZAP-70 protein and CD38 expression level, semiquantitative RT-PCR was used to detect LPL expression in peripheral blood samples of 58 Chinese patients with CLL. IgVH somatic mutational status was detected by multiplex PCR and sequencing of purified PCR amplification products. Flow cytometry was employed to determine the expression of ZAP-70 protein and CD38. Fluorescence in situ hybridization (FISH) was used to detect genomic aberrations. Results: LPL expression level was significantly correlated with IgVH mutational status (r = 0.348, P = 0.010), Binet stages (r = 0.276, P = 0.036), ZAP-70 protein (r = 0.431, P = 0.001) and CD38 (r = 0.546, P<0.001). Patients with unmutated IgVH genes had higher expression of LPL than did patients with IgVH mutations. The higher expression level of LPL was also associated with higher level of ZAP-70 and CD38, and more aggressive Binet stage. We also analyzed LPL expression in different cytogenetic subgroups. Higher LPL level was found in patients with unfavorable cytogenetic aberrations (deletion in 17p13 or 11q22) in contrast to lower level in good risk cytogenetics (deletion in 13q as the sole abnormality) (r = 0.404, P = 0.002). Conclusions: It was showed that LPL expression correlates with IgVH mutational status and other clinical or laboratory prognostic factors, and might be applied for the assessment of prognosis in patients with CLL. No significant financial relationships to disclose.
Alterations in the cell cycle checkpoint pathway in breast cancer.
Authors: Gargi Dan Basu, Tracey White, Janine R LoBello, Ahmet Kurdoglu, Subha Krishnan, Laura Gonzalez, Thomas Royce, Jeff Kiefer, Irene Cherni, Jessica Aldrich, Tyler Izatt, Megan Russell, Sara Nasser, John D. Carpten, David W. Craig, Michael J. Demeure
Journal: Journal of Clinical Oncology (2015)

126 Background: Breast cancer is a molecularly diverse disease with molecular subtypes defined by ER, PR and HER2 status. Dysregulation of the cell cycle pathway through activation of cyclin D1 and/or inactivation of CDKN2A is a mechanism of tumor progression in breast cancer and drugs targeting CDK4/6 is undergoing investigation in this disease with promising preliminary results. We investigated several key genetic alterations in cell cycle regulatory proteins in advanced breast cancer patient samples to identify potential targets for cell cycle related treatment options. Methods: A comprehensive genomic profiling was performed on 37 breast cancer samples with the majority being metastatic. Testing included targeted exome sequencing of 562 genes in tumor and paired normal DNA. Results: Patients’ ages ranged from 27-66 years. Analysis of cell cycle regulatory genes revealed focal amplification of cyclin D1/D2 or CDKN2A loss in 9/37 (24%) of cases, of which, 45% were hormone receptor (HR) positive, HER2 negative, 33% were HR positive, HER2 positive and 22% were triple negative (TNBC) subtype. Loss of RB1 was analyzed since it negatively regulates response to CDK4/6 inhibitors. Loss of RB1 was noted in 4/37 (10.8%) of cases, all of which were TNBCs. Only a single TNBC with RB1 loss had concurrent CDK4 amplification and loss of CDKN2A. No evidence of CCNE1 amplification was found in any samples. Incidence of CDK4 and CDK6 amplification was found in samples with cyclin D1 amplification or CDKN2A loss. Our cohort included a single male TNBC patient who harbored cyclin D1 amplification as well as CDKN2A loss. Overall, amplification of cyclin D1, cyclin D2, CDK4 and CDK6 was found in 16%, 5.4%, 2.7% and 2.7% respectively. Loss of CDKN2A was noted in 5.4% of tumors profiled. Conclusions: Exome sequencing identified subsets of patients with mutated cell cycle associated genes that may benefit from CDK 4/6 inhibitors. Our data suggests loss of RB1 is more frequent in TNBC subtype which may confer resistance to CDK4/6 inhibitors. Our analysis suggests that in addition to HR positive, HER2 negative patients, a subset of HR positive, HER2 positive patients could be sensitive to CDK4/6 inhibitors due to activation of the cell cycle pathway as evidenced by mutations in key genes.
Influence of KRAS and BRAF mutational status and rash on disease-free survival (DFS) in patients with resected stage III colon cancer receiving cetuximab (Cmab): Results from NCCTG N0147.
Authors: S. R. Alberts, S. N. Thibodeau, D. J. Sargent, M. R. Mahoney, F. Sinicrope, A. F. Shields, E. Chan, R. M. Goldberg, S. Gill, M. S. Kahlenberg, J. T. Quesenberry, T. C. Smyrk, A. Grothey, S. G. Nair
Journal: Journal of Clinical Oncology (2011)

3607 Background: Mutation (mut) of KRAS and BRAF negatively influence response to Cmab in metastatic colorectal cancer with the possible exception of KRAS Gly13Asp (JAMA 304:1812). Incidence of rash has served as a biomarker of a positive response to Cmab. N0147 assessed FOLFOX alone (arm A) or with Cmab (arm D) in resected stage III colon cancer. Impact of KRAS and BRAF mut status, and rash, on 3 yr DFS was assessed individually and jointly. Methods: Tissue from patients (pts) enrolled in N0147 was evaluated for mut in KRAS using the DxS mutation test kit KR-03/04 assessing for 7 different potential mut in codons 12 and 13. The V600E BRAF mut was assessed using an automated sequence technique. CTCAE v3.0 was used to classify and grade skin rash. Results: 2,580 pts were evaluable for KRAS analysis; 2516 for BRAF. See table for DFS based on KRAS and BRAF status. Pts with wtKRAS and wtBRAF had a DFS of 76% and 72% in arms A and D, respectively. 9% of pts treated with Cmab had Gr 3+ rash, with a nonsignificant trend toward increased DFS with rash in wtKRAS and wtBRAF groups (3 yr DFS in pts with rash 76% versus no rash 69%, p=0.26). Conclusions: Pts with wtKRAS and wtBRAF did not benefit from Cmab added to FOLFOX. None of the different KRAS mut predicted improved DFS with Cmab. DFS for pts with mutBRAF was similar to that for mutKRAS. Gr3+ rash was associated with some trend toward improved DFS with Cmab. Supported by NIH Grant CA25224, Bristol-Myers Squibb, ImClone, Sanofi-Aventis, and Pfizer. Group Arm (N) 3-yr DFS (%) HR (95% CI) P value KRAS WT A (909) D (954) 75 72 1.2 (0.9-1.4) 0.19 Gly13Asp Mut A (88) D (78) 67 56 1.4 (0.8-2.4) 0.19 Gly12Asp Mut A (139) D (130) 70 69 1.1 (0.7-1.7) 0.74 Gly12Val Mut A (77) D (79) 64 69 0.9 (0.5-1.6) 0.64 Other mutations A (70) D (56) 66 60 1.3 (0.7-2.3) 0.38 BRAF WT A (1093) D (1076) 72 70 1.2 (1-1.4) 0.08 V600E Mut A (155) D (192) 67 69 1.1 (0.8-1.7) 0.56 Both KRAS/BRAF WT A (736) D (743) 76 72 1.2 (1-1.6) 0.11 Abbreviations: WT, wild-type; Mut, Mutation; HR, hazard ratio; CI, confidence interval.
Long-term effects of the diagnosis and treatment of breast cancer upon young breast cancer survivors.
Authors: P. K. H. Morrow, A. C. Broxson, M. Munsell, K. Basen-Engquist, C. K. Rosenblum, L. H. Nguyen, L. R. Schover, K. Hahn, J. K. Litton, G. N. Hortobagyi
Journal: Journal of Clinical Oncology (2011)

9045 Background: Approximately 25% of women diagnosed with breast cancer are age 50 years (yrs) or younger. Studies have shown that, in comparison to older patients, the diagnosis and treatment of breast cancer has greater impact on mental health, social functioning, and psychological well-being in younger women. Methods: Utilizing the Breast Cancer Management System of the University of Texas MD Anderson (UTMDACC) Breast Medical Oncology Department, we identified women who had been evaluated at UTMDACC and were ≤45 yrs at time of diagnosis of breast cancer. Each patient was mailed a survey comprised of: the Quality of Life in Adult Cancer Survivors (QLACS) survey, Menopause Symptom Scale (MSS), and questions assessing pertinent background information. We used descriptive statistics to summarize QLACS and MSS data. Regression methods were used to model QLACS total score as a function of years since diagnosis, MSS total score, race/ethnicity, and background factors. Results: 1116 (49.8%) patients completed the survey. Mean age at diagnosis was 39.6 yrs (SD: 5), and age at time of survey was 47.6 yrs (SD: 6.8). 54.9% had received chemotherapy, and 55.1% had taken endocrine therapy. Clinical stages were: I (27.4%), II (33.6%), III (13%), and IV (5.6%), and unknown/missing (20.4%). Analysis of QLACS scores demonstrated that, compared to white women, black women demonstrated higher levels of social avoidance (p=.0058) and financial difficulty (p=.0009). Hispanic women had poorer scores on family-related distress (p=.0026) and cancer specific distress (p=.0076). Women diagnosed at age ≤40 yrs had significantly less sexual interest (p=.0014) after treatment than women over 40 yrs. Stage, adjuvant chemotherapy, endocrine therapy, and type of surgery were not significantly correlated with quality of life, as measured by the QLACS. Conclusions: Age and race had greater effect upon quality of life (QOL) of young breast cancer survivors than treatment modalities such as chemotherapy, endocrine therapy, and type of surgery. These findings highlight the importance of individualized approaches to improvement of QOL in young breast cancer patients, with special emphasis upon demographics.
Evaluation of process control in radiation oncology treatment planning.
Authors: Henry Wagner, Maria Singer, Jamie Knipple, Amy Aurand, Paulette Repella, Michele Ferenci
Journal: Journal of Clinical Oncology (2012)

186 Background: ROTP extends from simulation (SIM) through the start of treatment and constitutes a sequence of processes. Accurate implementation of each of these is essential for proper treatment. Prior guidelines had been proposed in our department for conformal treatment and intensity modulated radiation therapy (IMRT) or Volumetric Modulated Arc Therapy (VMAT); these were often not met leading to dissatisfaction by staff and patients. To improve this we evaluated the current steps in ROTP in an effort to improve our process. Methods: We analyzed the records of 157 eligible patients who underwent CT simulation from 1/1/12 through 3/30/12, excluding patients treated for benign disease, brachytherapy, or patients who never started treatment. The departmental standard was for urgent cases to start within 4 days (d), non-IMRT cases to start in 5d and IMRT/VMAT/SBRT cases to start in 10d. We defined three intervals, from SIM to start of treatment, SIM to approval of the plan by the physician, and approval to treatment start. Results: The median interval between planning landmarks in work-days and the % exceeding planning standards plus 2 days are shown below. Almost half of cases exceeded departmental standards for timeliness of ROTP. Much of the variability occurred after the physician had approved the plan. Conclusions: To improve timeliness of ROTP we have introduced changes in our planning process: 1. Strict definition of urgent cases. 2. Assigning a start date at the time of simulation. 3. Case planning review by the Radiation Oncologist, dosimetrist (+/- Physicist) at SIM. 4. Daily review of task list by Chief of Physics and Department Chair. These changes have been implemented in our department and results of the first two months of their use will be presented. [Table: see text]
The influence of treatment facility volume on the mortality of multiple myeloma patients.
Authors: Ronald S. Go, Adam C Bartley, Cynthia S Crowson, Nilay D. Shah, Elizabeth B. Habermann, Sara Holton, David R Holmes
Journal: Journal of Clinical Oncology (2016)

284 Background: MM is an uncommon cancer with annual incidence of only 27,000 cases in the US. Our study determined the extent to which the number of MM patients treated annually in a treatment facility affected all-cause mortality. Methods: We used the National Cancer Data Base (NCDB) to identify adult patients with MM diagnosed from 2003-2011. NCDB is sourced from over 1,500 Commission on Cancer-accredited cancer registries representing 70% of cancer cases in the US. We classified treatment facilities by quartiles based on facility volume (mean patients/year): Quartile 1 (Q1: &lt; 3.6), Quartile 2 (Q2: 3.6-6.1), Quartile 3 (Q3: 6.1-10.3) and Quartile 4 (Q4: &gt; 10.3). We used hot deck imputation to account for missing data, Cox regression to analyze the association between facility volume and time-to-death, and random intercepts to adjust for multiple patients per facility. Results: There were 94,722 MM patients cared for at 1,333 facilities. Most patients (73.5%) were diagnosed and treated in the same facility. The median age at diagnosis was 67 years and 54.7% were males. The median annual facility volume was 6.1 patients/year (IQR: 3.6-10.3; range: 0.2-109.9). The distribution of patients according to facility volume was Q1 (5.2%), Q2 (12.6%), Q3 (21.9%) and Q4 (60.3%). The unadjusted median overall survival by facility volume was: Q1: 26.9 months, Q2: 29.1 months, Q3: 31.9 months and Q4: 49.1 months. After multivariable analysis adjusting for demographic (sex, age, race, ethnicity), socioeconomic (income, education, insurance type), geographic (area of residence, treatment facility location), co-morbidity (Charlson-Deyo score), and disease-specific (year of diagnosis) factors, we show that facility volume remains an independent predictor of all-cause mortality. Compared to patients treated at Q4 facilities, patients treated at lower quartile facilities had a higher risk of death (Q3 HR: 1.16 [95% CI, 1.12-1.20]; Q2: 1.21 [1.17-1.26]; Q1: 1.27 [1.22-1.34]). We observed an inverse volume-outcome relationship up to an annual facility volume of approximately 60 patients. Conclusions: MM patients treated at higher volume facilities had lower risk of mortality compared to those treated at lower volume facilities.