tbuckley/cabot-search huggingface dataset:
Phase II trial evaluating the use of 21-gene recurrence score (RS) to select preoperative therapy in hormone receptor (HR)-positive breast cancer.
Authors: Amelia Bruce Zelnak, Sujatha Murali, Toncred Marya Styblo, Grant Walter Carlson, Sheryl G. A. Gabram, Monica Rizzo, Mylin Ann Torres, Mary Newell, Yuan Liu, Ruth O'Regan
Journal: Journal of Clinical Oncology (2013)

562 Background: Hormone receptor (HR)- positive breast cancer patients (pts) typically have lower pathological responses to pre-operative chemotherapy than HR-negative breast cancers. Objective: We evaluated the pathologic and radiologic response rates to pre-operative endocrine therapy or chemotherapy, as directed by RS, in pts with HR-positive resectable breast cancers. Methods: Pts with HR-positive breast cancers had RS performed on the initial diagnostic biopsy. Pts were treated pre-operatively as follows based on RS: ≤10, exemestane +/- goserelin for 6 to 12 months (ET); 11 to 25 randomized to ET or docetaxel-cyclophosphamide (TC) for 6 cycles (CT); ≥ 26, CT. Results: From 4/2009 to 12/2012, 66 pts signed consent for RS testing and 46 are evaluable for efficacy analysis. Median age is 57 (40 to 78); one-third of pts are African-American; 41% have clinically node positive disease. RS ranged from 2 to 57. 28 pts received CT: Pathologic complete response (PCR) rate was 10% and 60% of cancers were down-staged based on initial T-stage. Radiologic response is available for 20 pts: complete radiologic response (CRR) 15%, partial RR (PRR) 40%, progressive disease (PD) 5%. In 11 pts with RS 11 to 25: PCR 0%, down-staged 45%, up-staged 18%, radiologic responses: CRR 17%, PRR 50%, PD 17%. In 17 pts with RS ≥ 26: PCR 18%, down-staged 71%, up-staged 0%, radiologic responses: CRR 14%, PRR 36%, PD 0%. 18 pts received ET for between 6 to 22 months, 5 remain on study and have not had surgery: PCR 0%; down-staged 38%; up-staged 15%; radiologic responses: CRR 13%, PRR 40%, PD 0%. There was no correlation between RS and efficacy of ET. To date, 3 pts have relapsed, all of whom received CT. Conclusions: This is the first prospective use of the 21-gene RS to select pre-operative therapy for pts with HR-positive breast cancer. Pre-operative CT results in tumor down-staging in the majority of cancers with RS ≥ 11, though it appears to be more effective with RS ≥ 26. ET was moderately effective in down-staging cancers with RS ≤ 25. Updated results will be presented. Clinical trial information: NCT00941330, NCT00832338.
Imageable orthothopic metastatic mouse models for the identification of the antitumor and antimetastatic efficacy of traditional Chinese medicine (TCM).
Authors: Lei Zhang, Chengyu Wu, Yong Zhang, Xiaoen Wang, Jose Reynoso, Robert M. Hoffman, Ming Zhao
Journal: Journal of Clinical Oncology (2012)

e14700 Background: Traditional Chinese Medicine (TCM) is still poorly understood with regard to the types of cancer it is effective against, as well as its mechanism of action. Modernization of TCM evaluation is necessary in order for TCM to be effectively developed. We report here on the use of patient-like orthotopic nude-mouse models of metastatic cancer to obtain proof-of-concept that TCM combinations can have anti-tumor and anti-metastatic activity. Methods: In the present study, human and mouse lung cancer and pancreatic cancer cell lines (H460, Lewis lung carcinoma [LLC] and MIA-PaCa-2, respectively), labeled with red fluorescent protein (RFP) or green fluorescent protein (GFP) were used. The cells were initially implanted subcutaneously or injected in the tail vein in nude mice. Subcutaneous tumors were harvested to obtain tissue fragments which were implanted orthotopically in nude mice. These models were used to evaluate the anti-tumor and anti-metastatic efficacy of the TCM termed Fufang LQ (LQ), which contains a mixture of Chinese herbs. Results: LQ (gavage, 600 mg/kg/day) significantly inhibited pancreatic and lung cancer tumor growth as measured by imaging, tumor and weight in both subcutaneous and orthotopic models. LQ was significantly efficacious against primary and metastatic cancer in the above models without weight loss in contrast to drugs such as doxorubicin and cisplatin, which caused significant weight loss. Survival of tumor-bearing mice was also prolonged by LQ treatment. Conclusions: The results of the present study indicate that TCM can have non-toxic efficacy, in contrast to standard chemotherapy drugys, against metastatic pancreatic and lung cancer in clinically-relevant orthotopic mouse models of cancer, an important step toward the clinical development of TCM.
A prospective comparison of times to presentation and treatment of rural and urban head and neck cancer patients in Queensland, Australia.
Authors: Zulfiquer Ali Otty, Sabe S. Sabesan, Suresh Chandra Varma, Abhishek Jagdish Joshi
Journal: Journal of Clinical Oncology (2014)

6539 Background: Rate of survival from head and neck (H and N) cancer is lower among rural patients compared with their urban counterparts. This study’s aim was to examine whether there was any difference between Urban (U) and rural (R) areas in the time taken to receive various aspects of H and N cancer management. Methods: H and N cancer patients presenting to Townsville, Cairns and Mackay hospitals were prospectively recruited from January 2009 to January 2011. The demographic factors as well as median times between 1) symptoms and first consultation, 2) symptoms and referral to specialist, 3) symptoms and visit to specialist, 4 ) symptoms and first treatment, 5) diagnosis and first treatment, 6) consultation and referral to specialist, and 7) visit to specialist and treatment, were collected. Fisher’s, Kruskal-Wallis and Mann-Whitney tests were used to compare the two groups. Results: Out of the total of 158 patients , 62 % were living in urban and 37.3 % were living in rural areas. According to univariate analysis, there was significant difference in median time between diagnosis and first treatment between U and R areas (p=0.015). Indigenous patients had significant delays from diagnosis to first treatment (p=0.013), and visit to a specialist and treatment (p=0.031), compared to non-indigenous patients. According to multivariate analysis, there was significant delay in time between symptoms and first treatment in low-income compared to high-income population (P =0.03) and in patients with lower level of education compared to those with higher level of education ( P=0.04). There was significant delay in time between diagnosis and treatment for patients living in R area compared to those living in U area (P=0.028). The time between first consultation and referral to a specialist and time between visit to specialist and treatment was significantly longer in patients living in R areas compared to U area ( P=0.025 and P=0.003). Conclusions: There are delays in various aspects of head and neck cancer management depending on remoteness of residence and socio-economic factors. Improvement in management pathways for rural patients may improve their survival rates from H and N cancer.
Contribution of diet and physical activity to metabolic parameters among survivors of childhood leukemia.
Authors: Emily S. Tonorezos, Debra A. Kent, Chaya S. Moskowitz, Kevin C. Oeffinger
Journal: Journal of Clinical Oncology (2012)

9552 Background: Survivors of childhood acute lymphoblastic leukemia (ALL) are at increased risk for obesity, insulin resistance and increased visceral adiposity. A history of cranial radiation therapy (CRT) worsens this risk. In non-cancer populations, adherence to a Mediterranean Diet has been shown to improve metabolic parameters and risk of diabetes mellitus. Whether diet may contribute to insulin resistance and increased adiposity in ALL survivors is not known. Methods: We surveyed 117 adult survivors of childhood ALL using the Harvard Food Frequency Questionnaire. Physical activity energy expenditure (PAEE) was measured with the SenseWear Pro2 Armband. Fasting blood was obtained on all subjects and insulin resistance was estimated using the Homeostasis Model for Insulin Resistance (HOMA-IR). Visceral adiposity was measured by abdominal CT. Adherence to a Mediterranean Diet pattern was calculated using the index developed by Trichopoulou. Subjects were compared using univariate analysis. Results: Subjects were majority female (56%); 25% were minority or Hispanic white. A history of CRT was present in 15 (29%) men and 25 (38%) women. Among all subjects, greater adherence to a Mediterranean diet pattern was associated with improved HOMA-IR (p=0.14), visceral adiposity (p=0.03), subcutaneous adiposity (p=0.005), waist circumference (p=0.02), and body mass index (p=0.03) (all unadjusted analyses). The effect of adherence to a Mediterranean diet on insulin resistance was especially notable in men who did not receive CRT (p=0.06). Higher dairy intake was found to worsen HOMA-IR (p=0.014), but other individual components of the Mediterranean diet, such as low intake of meat and high intake of fruits and vegetables, were not significant. Inclusion of PAEE did not alter our findings, although higher PAEE was associated with lower body mass index. Conclusions: Adherence to a Mediterranean diet pattern, especially low consumption of dairy products, may improve insulin resistance in survivors of childhood ALL. Further study is warranted.
Baseline quality of life as a prognostic factor for overall survival in lung cancer patients
Authors: X. Zhao, J. Sloan, P. Yang, D. Sargent, J. Wampfler, Y. Shao
Journal: Journal of Clinical Oncology (2009)

e19031 Background: Useful predictors of survival in cancer patients have been found including such as gender, race, age, marital status, state of disease and tumor location. We set to explore the prognostic value of baseline QOL assessments on overall survival in lung cancer patients. Methods: A total of 1,319 lung cancer patients were followed at Mayo Clinic between 1997 and 2007. Overall QOL was assessed by either Lung Cancer Symptom Scale (LCSS) or a single-item Linear Analogue Self Assessment (LASA) with comparable wording. QOL scores were transformed to a 0–100 scale with higher scores representing better status. Patients QOL scores assessed within the first 6 months of follow-up were dichotomized using a priori definition for clinically deficiency score (CDS, ≤50 vs. &gt;50). The Kaplan-Meier method was used to estimate the distribution of survival times by QOL clinical deficient categorization. Cox Proportional Hazards Models were used to evaluate the prognostic importance of QOL on OS alone and in the presence of age, smoking category, gender, treatment, stage of disease, smoking cessation and years of consuming a pack every day. Results: Baseline QOL was significantly associated with OS univariately (HR=0.46 with p&lt;0.0001 based on the CDS categorization). After controlling for all these other factors, the indication of a clinically deficient baseline QOL contributed significantly to the prediction of patient survival (p=0.0002; HR=0.67). Age, treatment, disease stage, smoking cessation and smoking category were also significant predictors of OS multivariately. The median survival for patients that had an overall QOL score less than the CDS (≤50) was 1.6 versus 4.6 years for patients with QOL &gt;50. Conclusions: Baseline overall QOL measured by LCSS or LASA is a significant and independent prognostic factor for OS in lung cancer patients. A meaningful next step in this research is to investigate interventions to improve lung cancer patient QOL and thereby increase their likelihood of survival as well. No significant financial relationships to disclose.
A phase I study of temsirolimus (TEM) and bryostatin (BRYO) in patients with metastatic renal cell carcinoma (RCC)
Authors: E. R. Plimack, Y. Wong, M. Von Mehren, L. Malizzia, S. K. Roethke, T. Li, S. Litwin, G. R. Hudes, N. B. Haas
Journal: Journal of Clinical Oncology (2009)

5111 Background: TEM, an inhibitor of mTOR complex 1 (TORC1), is approved for the treatment of metastatic RCC. BRYO inhibits protein kinase C, a downstream effector of mTOR complex 2 (TORC2). We observed additive effects of TEM and BRYO against RCC in vitro. Methods: Four cohorts of 3–6 patients (pts) received weekly BRYO (20 mcgm/m2) and TEM (10, 15, 25, or 37.5 mg,) in 28 day cycles. DLT was defined as 1st cycle toxicity ≥ grade 3. Results: Twenty-three pts have been enrolled. Eighteen pts had RCC: clear cell (12), papillary (3), clear cell with sarcomatoid/spindle features (2), unclassified (1), Among RCC pts, 3 had no prior therapy. 15 had a median of 2 prior therapies (immunotherapy, TKIs, and/or bevacizumab). To date, 22 pts have received 103 cycles across 4 dose levels. Five non-RCC pts (4 sarcoma, 1 paraganglioma) received up to 3 cycles of treatment. Two of these pts (both had prior cytotoxic therapy) experienced DLT at 15 mg (Gr 3 neutropenia and Gr 3 hypophosphatemia) Subsequently, pts with prior cytotoxic therapy were excluded. One additional non-RCC pt (prior radiation) experienced DLT (Gr 3 neutropenia) at TEM 37.5 mg. Among RCC pts, there were no 1 st cycle DLT's. Significant toxicities during later cycles included Gr 3/4 thrombosis at TEM 37.5 mg (2), Gr 4 thrombus/Gr 4 LV dysfunction at TEM 15 mg (1), and Gr 3 dyspnea/Gr 3 pneumonitis at TEM 10mg (1). Gr 4 hypercholesterolemia (1) and Gr. 4 triglyceride elevation (1) were seen at TEM 37.5 mg, both reversed with treatment. One RCC pt withdrew prior to receiving treatment. Of the 17 remaining RCC pts, 3 had PRs and 9 had SD. One treatment naïve pt (TEM 15 mg) continues with PR for 2+ years after discontinuing treatment. One pt (had progressed on sunitinib) continues in a PR at 14+ months. Twelve pts received ≥4 cycles and 3 received &gt;10 cycles. PR was seen in both clear cell and papillary histologies. Median PFS was 7.8 months for all pts and 5.7 months for previously treated pts. Two pts, both with PR, remain on treatment, having received 18 and 8 cycles. Conclusions: The TEM/Bryo combination is feasible for multiple cycles on a weekly schedule at full doses of each agent with durable PR and SD in RCC refractory to other therapies. Enrollment continues to further characterize safety and efficacy. [Table: see text]
Italian Real Life Experience with Brentuximab Vedotin: Results of a National Observational Study on Relapsed/Refractory Anaplastic Large Cell Lymphoma
Authors: Cinzia Pellegrini, Luigi Rigacci, Caterina Patti, Guido Gini, Donato Mannina, Monica Tani, Chiara Rusconi, Alessandra Romano, Anna Vanazzi, Barbara Botto, Carmelo Carlo-Stella, Stefan Hohaus, Gian Matteo Rigolin, Pellegrino Musto, Patrizio Mazza, Stefano Molica, Paolo Corradini, Angelo Fama, Francesco Gaudio, Michele Merli, Angela Gravetti, Giuseppe Gritti, Annalisa Arcari, Patrizia Tosi, Anna Marina Liberati, Antonello Pinto, Vincenzo Pavone, Filippo Gherlinzoni, Virginia Naso, Stefano Volpetti, Andrea Visentin, Maria Cecilia Goldaniga, Maurizio Bonfichi, Amalia De Renzo, Corrado Schiavotto, Michele Spina, Sergio Storti, Angelo Michele Carella, Lisa Argnani, Pier Luigi Zinzani
Journal: Blood (2016)
Branched-chain amino acids enhance cyst development in autosomal dominant polycystic kidney disease
Authors: Junya Yamamoto, Saori Nishio, Fumihiko Hattanda, Daigo Nakazawa, Toru Kimura, Michio Sata, Minoru Makita, Yasunobu Ishikawa, Tatsuya Atsumi
Journal: Kidney International (2017)
Impact of age on the associations between genomic testing in breast cancer (BrCA) and chemotherapy (chemo) use and costs.
Authors: Yu-Ning Wong, Andrew J Epstein, Nandita Mitra, Anil Vachani, Sakhena Hin, Lin Yang, Aaron Smith-McLallen, Katrina Armstrong, Peter W Groeneveld
Journal: Journal of Clinical Oncology (2015)

6528 Background: The 21-gene recurrence score assay (Oncotype Dx) (RS) guides adjuvant chemo use in patients (pts) with BrCA. Since age is associated with chemo appropriateness, we sought to understand if the associations between RS receipt, chemo use, and costs varied by age. Methods: We identified 7665 pts diagnosed with node-negative, hormone-receptor-positive BrCA during 2007-2010 using the Pennsylvania Cancer Registry and claims from Independence Blue Cross (IBC) or Medicare for 12 months before and after diagnosis. Propensity-score-weighted regression models were used to assess the independent effect of RS receipt on chemo use and total 1-year post-diagnosis chemo costs by age group, controlling for demographics, insurance, tumor characteristics, and comorbidities. Results: Mean age was 71 years (range 23-100). 74% were insured by Medicare. Pts who received RS were younger, had fewer comorbidities, were more likely Stage 1, and were more likely to have IBC coverage (p < .001 for all). The proportion of patients undergoing RS testing increased from 17% among pts in 2007 to 28% in 2010. RS use was associated with reduced adjuvant chemo use and lower chemo spending among younger pts, but had minimal effects on chemo use and chemo spending among older pts (Table, * indicates p < .05). None of the RS recipients over age 85 received chemo. Conclusions: RS testing was associated with lower chemo use in younger pts, but had little effect on chemo use in older pts. The cost savings noted in young pts who underwent the RS test was not seen among older pts. Our results suggest that RS testing is being ordered in many elderly patients for whom chemo is not a realistic treatment option. As additional high-cost genomic tests enter clinical practice, their use should be targeted towards pts in whom the test result will influence clinical decision making. Age RS testing N Received chemo % Difference in chemo rate Mean chemo spending ($) Difference in chemo spending ($) < 50 Yes 186 47 -18* 21000 -23000* No 297 65 44000 50-64 Yes 459 34 -9* 9500 -12500* No 673 43 22000 65-74 Yes 794 22 1 4100 -2200* No 1987 21 6300 75-84 Yes 300 14 5* 2100 200 No 2182 9 1900 ≥ 85 Yes 11 0 -2* 60 -130 No 776 2 190
A randomized, double-blind, multinational trial comparing denosumab with zoledronic acid for treatment of bone disease in adults with newly diagnosed multiple myeloma.
Authors: Noopur S. Raje, Evangelos Terpos, Brian G. Durie, Ramon Garcia-Sanz, Kazuyuki Shimizu, Wolfgang Willenbacher, Li Zhu, Ada H. Braun, Rajul K. Jain, Antonio Palumbo
Journal: Journal of Clinical Oncology (2014)

TPS8628 Background: A characteristic feature of multiple myeloma (MM) is bone destruction mediated by osteoclasts. This breakdown of bone releases factors that mediate myeloma cell growth, creating a cycle of skeletal damage and tumor cell growth. Patients with MM and bone lesions can experience debilitating pain and skeletal complications including pathologic fractures, need for radiotherapy or surgery to bone, and spinal cord compression, collectively termed skeletal-related events (SREs). RANKL is the key mediator of osteoclast activity. Denosumab, a fully human monoclonal antibody specific to RANKL, inhibits the formation, function, and survival of osteoclasts, thus decreasing cancer-mediated bone destruction. The primary endpoint of this trial is to determine whether denosumab is noninferior to zoledronic acid (ZA) in delaying the time to 1st on-study SRE in patients with MM. Secondary endpoints include superiority of denosumab vs ZA in delaying the time to 1st on-study SRE and time to 1st-and-subsequent SRE and overall survival. Safety endpoints will be assessed. This trial is registered (ClinicalTrials.gov NCT01345019) and sponsored by Amgen Inc. Methods: We are targeting enrollment of ~1520 adults with newly diagnosed MM and ≥1 bone lesion. Patients with ≤30 days of anti-myeloma therapy, ≤1 prior dose of IV bisphosphonate, an ECOG status ≤2, and adequate organ function are eligible. Use of any approved treatment regimen is permitted as anti-myeloma treatment in this trial. Enrolled patients are stratified by whether they intend to undergo autologous stem cell transplant; use of novel vs non-novel anti-myeloma agents as 1st-line therapy; stage at diagnosis per the International Staging System; SRE at time of presentation; and geographic region. Randomized (1:1) patients receive either SC denosumab 120 mg + IV placebo or IV ZA 4 mg (adjusted for CrCl) + SC placebo once every 4 weeks. Daily calcium (≥500 mg) and vitamin D (≥400 IU) supplements are strongly recommended. The primary analysis is planned when ~800 patients experience an on-study SRE. Enrollment is currently ongoing and enrollment rates are as planned. Clinical trial information: NCT01345019.
Clinical and translational investigation of pan-HDAC inhibition in advanced urothelial carcinoma (UC).
Authors: Sumati Gupta, Daniel Joseph Albertson, Timothy Parnell, Brian Dalley, John O Shea, Alexis Weston, Andrew Butterfield, Lisa M. Pappas, Joshua David Schiffman, Sunil Sharma, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2017)

379 Background: Pan-HDAC inhibitors were studied in two separate phase I pharmacokinetic solid tumor trials at Huntsman Cancer Institute. The objective of this study was to investigate the clinical efficacy of HDAC inhibition in those study subjects with UC and correlate response to molecular subtype of tumor with translational studies to validate clinical benefit. Methods: Patients with UC treated with a pan-HDAC inhibitor in two Phase I trials were included. RECIST 1.1 was used to categorize responses. Expression profiling and TCGA clustering were performed using archived tissue (obtainable for seven of the ten subjects). To elucidate the mechanisms of clinical benefit bladder cancer cell lines with varied mutational profiles and differential sensitivity to cisplatin were tested for sensitivity to panobinostat with characterization of phenotypic changes upon treatment. Results: Ten subjects with advanced UC received either belinostat or panobinostat. The best overall responses in the pooled data were: 1 complete response (CR), 1 partial response (PR), 6 stable disease (SD), 2 progressive disease (PD). The patient with CR had failed two prior lines of chemotherapy (including cisplatin), had a Cluster IV tumor and remains in CR for 3.5 years now. All tumors with SD belong to Cluster I. For those with SD, the progression free survival ranged from 6 to 7.5 months on treatment. One tumor with PR and one tumor with PD had characteristics partly consistent with Cluster III. Validating the broad spectrum of clinical activity of pan-HDAC inhibition, potent cytotoxicity with panobinostat was noted in bladder cancer cell lines with varied chromatin remodeling mutations. Panobinostat causes inhibition of colony formation, cell cycle arrest and proinflammatory cytokine release in these cells. Cisplatin-resistant HT1197 cells (with ARID1A mutation) are tenfold more sensitive. Conclusions: Pan-HDAC inhibition may be an effective treatment option in both luminal and basal subtypes of UC and in platinum-resistant setting. Translational studies suggest options for rational therapeutic combinations to enhance efficacy. HDAC inhibition may be particularly effective in UC with mutations affecting the SWI/SNF complex.