tbuckley/cabot-search huggingface dataset:
Trends in <i>BRCA1/2</i> mutation testing rates among young women and men with breast cancer, 2005-2012.
Authors: Kenneth L Kehl, Chan Shen, Jennifer Keating Litton, Banu Arun, Sharon Hermes Giordano
Journal: Journal of Clinical Oncology (2015)

103 Background: Guidelines recommend consideration of testing for germline mutations in the BRCA1/2 genes for certain patients with breast cancer, including women diagnosed under age 45 and male patients. However, there are limited data regarding rates of genetic testing in these patients on a population basis. Methods: Using insurance claims from the national MarketScan database of privately insured patients, we identified incident breast cancer cases among women age ≤ 40, women age 41-45, and men of all ages, diagnosed from 2005-2012. We assessed claims for BRCA1/2 testing using Kaplan-Meier analysis and a Cox proportional hazards model, compared across patient cohorts and years of diagnosis. Results: We identified 28,495 patients (11,198 women age ≤ 40, 15,929 women age 41-45, and 1,368 men) for analysis. BRCA1/2 testing rates increased with later years at diagnosis (log-rank P &lt; 0.001 for women age ≤ 40 and women age 41-45; P = 0.01 for men). Men had lower testing rates than women age 41-45, who in turn had lower rates than women age ≤ 40. Furthermore, among women diagnosed in earlier years, testing rates never approached those of patients diagnosed in later years, even after extended follow-up. For example, women age ≤ 40 diagnosed in 2005 had a testing rate by one year after surgery of 19.6% (95% confidence interval, CI, 17.0%-22.5%), and a rate by five years after surgery of 35.3% (95% confidence interval, CI, 31.1%-39.9%). However, for women age ≤ 40 diagnosed in 2009, the testing rate at one year was 57.1% (95% CI, 54.8%-59.5%; hazard ratio for testing, 3.40, 95% CI 2.95-3.92, compared to women age ≤ 40 diagnosed in 2005). Conclusions: Genetic testing rates among men and young women with breast cancer increased with time, but uptake of testing was uneven. Among young women, testing rates for survivors diagnosed in earlier years and followed over time never approached those of patients diagnosed later. These results demonstrate a need to better incorporate genetic counseling into survivorship care, and to promote awareness among providers that long-term breast cancer survivors may be eligible for genetic testing that was not offered or available when they were diagnosed.
External beam radiation therapy evaluated in patients with breast cancer with cutaneous mastocytosis.
Authors: Lisa Chaiken, Les Yonemoto, Ulrike Ziegner, Gilbert Kuhn, Maggie Lee DiNome, Randal Slates, Guy Juillard
Journal: Journal of Clinical Oncology (2014)

95 Background: Mastocytosis is a rare disease characterized by an excess of mast cells. The most common presentation is cutaneous mastocytosis (CM) presenting with skin lesions of urticaria pigmentosa (UP). There is concern of anaphylactic shock from the interaction of ionizing therapeutic radiation and mast cell activation in these patients. There is very little if anything published regarding radiation treatment of patients with cutaneous mastocytosis. Literature has ranged from radiation possibly causing mastocytosis in breast cancer patients to radiation treating canine mast cell tumors. Two patients are reported in order to explore and document the tolerance and safety of breast radiation in patients with cutaneous mastocytosis. Methods: Two patients with CM presented with early stage breast cancer for radiation treatment. Three dimensional conformal radiation to the breast was given. Epinephrine injection was kept at the patient’s side during treatment. With the initiation of radiation, a steroid and additional anti-inflammatory medicine or antihistamine were taken with the baseline medication, prior to each treatment. Monitoring was performed after treatment. To minimize potential toxicity, radiation started with the boost field to confirm acceptable tolerance. Results: Both patients tolerated the radiation without any unusual acute or late toxicities. There was no anaphylaxis. Both patients showed a decrease in the UP rash in the radiated field. Tryptase levels, a marker for CM, remained stable or decreased. Conclusions: Two patients with cutaneous mastocytosis showed excellent tolerance of breast radiation therapy. In the radiation field, UP improved and may be indicative of mast cells being sensitive to radiation in small volumes. Breast radiation avoids more extensive surgery and anesthesia, which are known to exacerbate CM. Radiation therapy to the breast appears to be safe for patients with cutaneous mastocytosis. Precautions of starting with the boost field, monitoring the patients, and maximizing medical treatment, should be taken given the limited data. This report is the first to document the safety of breast radiation in patients with cutaneous mastocytosis.
The effect of novel acridine-based agents with topoisomerase II inhibitor on mesothelioma cell proliferation and apoptosis.
Authors: A. Raza, B. A. Jacobson, M. Patel, A. Benoit, J. Jay-Dixon, D. M. Ferguson, R. A. Kratzke
Journal: Journal of Clinical Oncology (2011)

e13507 Background: Human topoisomerase II (hTopoII) inhibitors are important chemotherapeutic agents in many different settings including treatment of malignant mesothelioma. Commonly used topoisomerase inhibitors are hTopoII poisons like etoposide and doxorubicin. HTopoII poisons cause formation of covalent topoisomerase II-DNA complexes and induce DNA strand breaks which results in chromosomal translocations producing secondary malignancies. We have tested a small library of substituted 9-aminoacridine derivatives which are catalytic inhibitors of hTopoII. We have demonstrated that these agents inhibit proliferation and induce apoptosis in mesothelioma cell lines. Methods: Four mesothelioma cell lines (H513, H2373, H2461 and H2596) were grown in RPMI with 10% calf serum. LP9 (non malignant mesothelial cells) were grown in 1:1 ratio of MCDB: 199E medium supplemented with 15% calf serum, 0.4 µg/mL hydrocortisone, and 15ng/mL epidermal growth factor. We used CCK-8 kit (Dojindo inc.) to perform cell proliferation assays. Cells were treated with four compounds for 72 hours. Equal concentrations of DMSO were used as control. ADP-ribose polymerase1 (PARP) cleavage and Guava Nexin assay were used to show induction of apoptosis by these compounds. Results: Our results indicate that these compounds inhibit proliferation of mesothelioma cell lines with an EC50 range between 6.91 µM to 32.45 µM. These compounds are relatively non-toxic to non-malignant mesothelioma cells (LP9). We also demonstrated additive effect on cell proliferation when these compounds were combined with cisplatin. These compounds induce apoptosis in mesothelioma cell lines tested. Conclusions: These novel compounds inhibit mesothelioma cell growth in-vitro by inducing apoptosis. Furthermore, strand passage assay and DNA cleavage assay have already shown that these compounds are catalytic inhibitors of hTopoII and do not cause double strand breaks which are responsible for chemotherapy related secondary malignancies. EC50 values noted are difficult to achieve in-vivo but further modifications of these agents may help to produce more potent hTopoII catalytic inhibitors.
Nightly dosing of regorafenib.
Authors: Philip A. DeSimone, Colleen Overley, Katie E Long
Journal: Journal of Clinical Oncology (2015)

549 Background: Fatigue and anorexia are major side effects in the use of regorafenib. These effects are compounded in patients with metastatic colon cancer to the liver. Finding a good fit for this agent has been difficult in patients when used in third and fourth line treatments. Our clinic has treated 21 patients with this agent. Methods: After the first four patients’s experienced extreme fatigue and anorexia at the recommended starting dose of 160mg daily, it was decided to start at a 21 day dose of 120mg. Even at this starting dose, it was necessary to dose deescalate. Ten patients were treated at the 120 mg daily dose and escalated 160 mg daily if tolerated. The agent was given at night to take advantage of the sleep period and the diurnal variation in adrenal gland function. No patient was treated with oral corticosteroids. Results: Two patients previously treated and responders were retreated after they decided they would give the agent a second opportunity. One of these patients, on day two of receiving the agent, developed a severe rash and the treatment was stopped. One patient received the agent for one week before he decided to stop, but was experiencing no side effects. Eight patients were eligible for evaluation. All patients had metastatic disease to the liver. Six were treated for at least two months and two were treated only for one month. All therapy was discontinued because of progression of disease. Fatigue and anorexia were evaluated by a change in their ECOG performance status, fatigue criteria and weight change. ECOG performance status of the patients was, ECOG 1, one patient, ECOG 2, six patients, ECOG 3, one patient. The evaluation was done before, during and after each monthly treatment. No patient had a greater than 5% weight loss. Four patients had Grade 1 fatigue, (fatigue relieved by resting). Six of the eight patients were escalated to 160mg daily after two weeks. Conclusions: Although this is a small sample study, it appears that night time dosing may be effective in helping a patient to achieve maximum benefit of regorafenib therapy. This study did not address the changes in absorption caused by a light fat free meal taken at night, and does not take into consideration the possible change in half-life of the agent when taken at night.
Redesigning the transfer center process to adapt to increasing demands for services.
Authors: Pamela Bernice Douglas-Ntagha
Journal: Journal of Clinical Oncology (2012)

156 Background: Hospitals are faced with limited resources and a need to provide care to patients with the greatest needs. Methods: Develop a systematic approach for accepting external transfers to the appropriate setting of care based on clinical criteria Initiate communication between external physicians and accepting MDA (MD Anderson) physicians and ICU physicians as appropriate Identify a process for documenting clinical information to ensure appropriate and timely transfers to MDA Ensure policies and procedures align with EMTALA regulation. Results: MDA ICU physicians involved in the initial decision, as appropriate External transfer acceptance based on bed availability MDA physician must be physically present to manage transfer, conduct evaluation and develop treatment plan Incorporate into procedure telephone communication with external physician, TC Medical Director, MDA accepting physician (ICU and Pedi physician as appropriate) Operational definitions for routine and urgent have been established Non-emergent transfers occur weekdays between the hours of 8AM and 5PM Transfer Acceptance Form to capture clinical information was developed. Conclusions: Problem 1: Suboptimal Communication Developed a TC form. During first eight months of operation we achieved 85% compliance with regards to documentation of transfer. Compliance continues to trend upward. Problem 2: Placement of Patients in Appropriate Care Settings Decreased utilization of MDA Emergency Center beds noted as external transfer to inpatient beds increased. Problem 3: Sporadic Arrival of Non-emergent Transfers The majority of after-hours (between 5PM and 8AM) transfers were routine and urgent prior to project. After the intervention, the number of routine and urgent after-hours transfer trended downwards. After-hour emergent transfers increased indicating appropriate utilization of beds for patients with the greatest needs. Problem 4: Lack of Systematic Screening and Documentation Retrospective medical record audits of 100% of emergent transfers were conducted by the TCMedical Directors in collaboration with the Director of Patient Resources. 97% of emergent transfers were confirmed as emergent on retrospective review.
Adoption of neoadjuvant (NACT) and adjuvant chemotherapy (ACT) for bladder cancer: A population-based study.
Authors: C. M. Booth, D. R. Siemens, I. Tannock, Y. Peng, G. Li, W. J. Mackillop
Journal: Journal of Clinical Oncology (2011)

4644 Background: Evidence from clinical trials and international guidelines support the use of perioperative chemotherapy (CT) for patients with muscle-invasive bladder cancer undergoing cystectomy. Here we describe delivery of perioperative CT in the general population of Ontario, Canada. Methods: Electronic records of treatment were linked to the population-based Ontario Cancer Registry to identify all patients who underwent cystectomy for bladder cancer in Ontario 1992-2006. Census data concerning median household income were linked to the registry to provide an ecologic measure of socioeconomic status (SES). Utilization was compared across 3 study periods: 1992-96, 1997-01, 2002-06. Logistic regression was used to analyze temporal trends in the use of perioperative CT, while controlling for changes in case mix. Results: In 1992-2006 4,547 patients underwent cystectomy, of whom 736 (16%) received perioperative CT; NACT and ACT were used in 142 (3%) and 623 (14%) of cases respectively. While the use of NACT did not change over the 3 study periods (4%, 2%, 3%; p=0.080), utilization of ACT increased with time (10%, 15%, 16%; p<0.001). 79% of patients received cisplatin and 15% received carboplatin-based therapy; 43% received gemcitabine-cisplatin (GC) and 26% MVAC. Over the 3 study periods use of GC increased (0%, 17%, 78%, p<0.001) while use of MVAC decreased (38%, 47%, 5%, p<0.001). Use of perioperative CT varied widely across catchment areas of provincial cancer centers (11% to 22%, p<0.001). As expected, patients with lower stage disease and those with higher levels of comorbidity were less likely to receive CT (p<0.001), but after controlling for stage and comorbidity, older patients and residents of poorer communities were also significantly less likely to receive CT (p<0.001). Conclusions: Despite accumulating evidence and guidelines, perioperative CT remains substantially underutilized in the general population. The observed variations in use of CT across geographic regions and SES, may represent opportunities to target future interventions to increase utilization. We suggest that patients who are planned to undergo cystectomy for bladder cancer be reviewed by a multidisciplinary team.
Exome Sequencing Identifies Pxdn and DSP As Recurrently Mutated Genes in Infant ALL Patients Carrying a MLL-AF4 Translocation
Authors: Eddy HJ van Roon, Ronald Stam, Merel Willekes, Roland P. Kuiper, Rutger W.W. Brouwer, van IJcken F. Wilfred, Rob Pieters
Journal: Blood (2014)
Off-label indications for antidepressants in primary care: descriptive study of prescriptions from an indication based electronic prescribing system
Authors: Jenna Wong, Aude Motulsky, Michal Abrahamowicz, Tewodros Eguale, David L Buckeridge, Robyn Tamblyn
Journal: BMJ (2017)

Objective To examine off-label indications for antidepressants in primary care and determine the level of scientific support for off-label prescribing.Design Descriptive study of antidepressant prescriptions written by primary care physicians using an indication based electronic prescribing system.Setting Primary care practices in and around two major urban centres in Quebec, Canada.Participants Patients aged 18 years or older who visited a study physician between 1 January 2003 and 30 September 2015 and were prescribed an antidepressant through the electronic prescribing system.Main outcome measures Prevalence of off-label indications for antidepressant prescriptions by class and by individual drug. Among off-label antidepressant prescriptions, the proportion of prescriptions in each of the following categories was measured: strong evidence supporting use of the prescribed drug for the respective indication; no strong evidence for the prescribed drug but strong evidence supporting use of another drug in the same class for the indication; or no strong evidence supporting use of the prescribed drug and all other drugs in the same class for the indication. Results 106 850 antidepressant prescriptions were written by 174 physicians for 20 920 adults. By class, tricyclic antidepressants had the highest prevalence of off-label indications (81.4%, 95% confidence interval, 77.3% to 85.5%), largely due to a high off-label prescribing rate for amitriptyline (93%, 89.6% to 95.7%). Trazodone use for insomnia was the most common off-label use for antidepressants, accounting for 26.2% (21.9% to 30.4%) of all off-label prescriptions. For only 15.9% (13.0% to 19.3%) of all off-label prescriptions, the prescribed drug had strong scientific evidence for the respective indication. For 39.6% (35.7% to 43.2%) of off-label prescriptions, the prescribed drug did not have strong evidence but another antidepressant in the same class had strong evidence for the respective indication. For the remaining 44.6% (40.2% to 49.0%) of off-label prescriptions, neither the prescribed drug nor any other drugs in the class had strong evidence for the indication.Conclusions When primary care physicians prescribed antidepressants for off-label indications, these indications were usually not supported by strong scientific evidence, yet often another antidepressant in the same class existed that had strong evidence for the respective indication. There is an important need to generate and provide physicians with evidence on off-label antidepressant use to optimise prescribing decisions.
Integrative oncology consultation and symptom palliation: Analysis of patient-reported outcomes at a comprehensive cancer center.
Authors: Gabriel Lopez, Jennifer Leigh McQuade, Richard T. Lee, Jane Williams, Amy Spelman, Bryan Fellman, Yisheng Li, Eduardo Bruera, Lorenzo Cohen
Journal: Journal of Clinical Oncology (2016)

84 Background: Patients (pts) receiving cancer care are increasingly interested in complementary health approaches to improve symptoms and quality of life. We report on demographics and patient reported outcomes in an integrative oncology (IO) clinic. Methods: Pts presenting for IO consultation or follow-up completed: Measure Yourself Concerns and Wellbeing (MYCaW), Edmonton Symptom Assessment Scale (ESAS), Short Form 12 (SF-12) quality of life (QOL) scale, and an overall satisfaction questionnaire. Consultations were provided by medical oncologists. Results: 2,474 consultations were conducted from 9/2009 to 12/2013; 26.0% (n = 643) had ≥ 1 follow-up visit (mean 3.2; SD1.8). Most were female (69%) and white (75%); most frequent cancer types was breast (29%); 29% of pts had advanced disease. At baseline, ESAS scores were highest for Sleep (4.2; SD 2.8), Fatigue (4.0; SD 2.8), Well-Being (3.8 SD 2.6) and Anxiety (3.1; SD 2.9). Those with advanced disease had significantly higher baseline ESAS scores for pain, nausea, shortness of breath, and appetite; higher ESAS subscale scores for physical and global distress; lower SF-12 physical health scores; and were more interested in developing an integrative/holistic approach and appetite. Those with loco-regional disease were more interested in overall health, hot flashes, and dry mouth. For ESAS baseline scores ≥ 4 and follow up within 30 days of the initial consult, we observed overall improvement in ESAS symptoms (38-60% of pts with ESAS decrease ≥ 1). Overall satisfaction was high at both initial encounter (9.4; SD 1.3) and first follow up (9.5; SD 1.2). Patients were satisfied to very satisfied with how well MYCaW concern 1 and 2 were addressed: 8.0 (SD 2.2) and 9.1 (SD 1.8). No difference in overall satisfaction was observed comparing those with advanced vs loco-regional disease. Conclusions: Most pts presenting for integrative oncology consultation have early stage disease, relatively low symptom burden, and are most interested in support for overall health. Patients were overall very satisfied with how well their top concerns were addressed, with significant improvements in symptom distress.
Aberrant PDGFRA Signalling Is Sustained by An Autocrine Loop in Peripheral T-Cell Lymphoma Not Otherwise Specified
Authors: Pier Paolo Piccaluga, Maura Rossi, Aurora Esposito, PierLuigi Tazzari, Francesca Ricci, Claudio Agostinelli, Simona Righi, Anna Gazzola, Philip Went, Francesco Alviano, Gian Paolo Bagnara, P.L. Zinzani, Stefano A. Pileri
Journal: Blood (2008)
Vector analysis of bladder cancer patient setup utilizing a magnetic resonance image-guided radiation therapy (MR-IGRT) system.
Authors: Benjamin Walker Fischer-Valuck, Olga L Green, Hiram Alberto Gay, Sasa Mutic, Jeff M. Michalski
Journal: Journal of Clinical Oncology (2016)

412 Background: Inter and intra-fraction anatomy changes in patients undergoing radiation therapy (RT) for bladder cancer (BC) are common but have thus far been studied with implanted fiducial markers, limited quality 2-D orthogonal films and computed tomography (CT). The adverse impact of daily set-up variation could be more significant than appreciated. Our goal was to employ the soft tissue imaging capabilities of an integrated magnetic resonance image-guided RT (MR-IGRT) system to analyze daily positioning. Methods: Fourteen patients with BC were treated on a MR-IGRT system. Patient setup was performed via volumetric MR imaging with a resolution of 0.15 x 0.15 cm. Alignment was performed according to skin marks then shifts assessed by comparing the treatment volume from the planning CT to the daily MR image. 240 pretreatment MR images were analyzed and 3 shifts were recorded for each image. A vector shift was calculated by combining the square root of the combined sum of the shifts squared. Number of times that the vector of combined shifts would have exceeded the planning tumor volume (PTV) was recorded. Results: Daily volumetric MR imaging allowed for accurate alignment and daily monitoring of bladder volume and normal tissue anatomy. Recorded shifts of the treated volume were 0.9±0.5 cm in the right/left direction, 0.7±0.3 cm in the anterior/posterior direction, and 0.7±0.4 cm in the cranio-caudal direction. In 66 (28%) of cases the vector shift was initially greater than the PTV margin. For 2 patients, pre-treatment MR imaging revealed the tumor reduced in size and dose to the bowel would have exceeded constraints, and treatment adaptation was performed to reduce normal tissue toxicity. Using CTCAE criteria, no grade 3 or higher toxicities have been reported. Conclusions: Accurate and reproducible treatment delivery is required to avoid marginal misses to the target volume as well as excess dose to normal tissue. MR-IGRT allows for excellent soft tissue visualization which enables for the avoidance of potential setups errors by allowing daily alignment changes to ensure the target is included in the PTV. It also allows the ability to make treatment changes based on anatomy variations.