tbuckley/cabot-search huggingface dataset:
Information preferences of women with triple-negative breast cancer (TNBC).
Authors: Kathleen Dickerson Swiger, Jocelyn A. Sendecki, Janine E. Guglielmino, Hope S. Rugo, Susan M. Domchek, Carey K. Anders, Carrie Tompkins Stricker, Hillary C.M. Nelson, Arin Ahlum Hanson, Hayley Dinerman, Catherine Creme Henry
Journal: Journal of Clinical Oncology (2015)

e20585 Background: In 2013 Living Beyond Breast Cancer (LBBC) began a comprehensive needs assessment of women with TNBC. Methods: LBBC fielded an online 80-question survey from November 25, 2013-January 10, 2014 to determine education and support needs of women with TNBC. Women with other breast cancer subtypes were included to allow for comparison; subtypes were self-reported. Respondents were asked for their preferences for tailored information. TNBC respondents were asked to rate the difficulty of finding TNBC-specific informational resources as “not all easy,” “somewhat easy,” “easy,” or “very easy.” Additionally, women with TNBC were asked what sources they used to find TNBC-specific information. Simple logistic regression was used for the analysis. Results: A total of 2,610 responses were analyzed: 656 (25.1%) identified as TNBC and 1,954 (74.9%) as non-TNBC. Compared to women with other subtypes, women with TNBC had a significantly stronger preference for information tailored to breast cancer subtype (71% vs. 49%, p < 0.001). Of those with TNBC, only 6.69% reported TNBC-specific information was very easy to find, compared to 22.05%, easy; 54.92%, somewhat easy; and 16.34%, not at all easy. The top five sources of information were: online resources (62.5%), educational brochures (42.4%), current research updates (38.1%), online message boards (30.8%), and social media (29.7%). Conclusions: Women with TNBC strongly prefer that breast cancer information be tailored to their subtype, but they report difficulty in finding TNBC-specific information. When rating methods of information access, women with TNBC overwhelmingly prefer online resources. Healthcare professionals, cancer centers and breast cancer organizations should consider developing educational programs and materials that specifically target women with TNBC and are available electronically.
Results of autologous transplants for children from a tertiary cancer center in India.
Authors: Amol Dongre, Randeep Singh, Ravi Shankar Thippeswamy, Gautam Goyal, Sadhna Kannan, Bhausaheb Pandurang Bagal, Jayant Shankar Gawande, Purna Arun Kurkure, Shripad Banavali, Navin Khattry
Journal: Journal of Clinical Oncology (2012)

9559 Background: Autologous transplantation is a curative option for children with various malignancies. We report the results of our center with the aim of evaluating toxicities and prognostic factors that may influence decision making to use our limited resources judiciously. Methods: Forty-six patients diagnosed below 18 years from 1 st April 1994- 28 th February 2011 were included in this retrospective study. Twenty-four patients had lymphoma, 12- neuroblastoma and 10-others ( 5- acute leukemia, 4- Ewing sarcoma and 1 - rhabdomyosarcoma). Twenty-eight patients received peripheral blood stem cells, 12 – marrow and 6-both. Prognostic factors evaluated for overall survival (OS) and progression-free survival (PFS) were remission status at transplant, baseline and pre-transplant serum albumin, time interval between diagnosis and transplant, type of malignancy and number of lines of chemotherapy pre transplant. Results: Median age at diagnosis and transplant were 9 and 12 years respectively. Median baseline and pre transplant serum albumin were 3.6 and 3.9 g/dl. Median number of lines of chemotherapy was 2. Median time from diagnosis to transplant was 1.1 years. Incidence of grade 3 and 4 oral mucositis and diarrhea were 46% and 25% respectively. At the time of transplant, 45% were in complete remission (CR), 41% in partial remission (PR) and 13% in refractory state. Total Parenteral Nutrition (TPN) was used in 63% patients with median duration of 11 days. No patient developed sinusoidal obstruction syndrome.Median days to neutrophil and platelet engraftment were 11 and 15 days respectively. Neutropenic sepsis leading to death was seen in 17%. Median follow up was 1.5 years. At 2 years, the probability of OS and PFS were 39% and 35% for all patients while OS and PFS for lymphoma, neuroblastoma and others were 45% and 32%, 17% and 0% and 50% and 40% respectively. CR at transplant was the most important determinant of better OS (59 % vs 28%; p = 0.000004) and PFS (53% vs 8%; p = 0.0000018). Conclusions: CR at transplant is the most important prognostic factor. Patients with neuroblastoma have dismal outcome which requires reevaluation of transplant strategies for this group.
Molecular profiling and targeted therapy in advanced endometrial cancer.
Authors: Michelle K. Wilson, Philippe L. Bedard, Anthony M. Joshua, Helen Mackay, Marcus O. Butler, Neesha C. Dhani, Stephanie Lheureux, Cristina Martin-Lorente, Victor Rodriguez-Freixinos, Blaise Clarke, Patricia Shaw, Anca Milea, Lisa Wang, Suzanne Kamel-Reid, Tracy Stockley, Jeff Bruce, Trevor John Pugh, Amit M. Oza
Journal: Journal of Clinical Oncology (2015)

5589 Background: Recurrent endometrial cancer (EC) has a poor prognosis with few effective systemic therapies. We reviewed the outcomes of advanced EC pts in an ongoing institutional molecular profiling program. Methods: DNA from blood and tumor (archival FFPE tissue) from EC pts (ECOG ≤ 1) was genotyped with a recurrent mutation(s) (mut) assay (Sequenom MassArray, 23 genes, 279 mut) or a NGS assay (Illumina TruSeq Amplicon Cancer Panel, 48 genes) in a CAP/CLIA certified laboratory. Whole exome DNA sequencing (germline and tumor) was performed in pts with exceptional responses. Results: From 3/2011 to 8/2014, 77 pts were enrolled: 43% type 1 endometrioid, 57% type 2 non-endometrioid. Median BMI was 29, 11 (14%) had diabetes, 69 (90%) had ≥ 1 line of chemotherapy. Somatic mut were seen in 64 pts (83%), 40 pts (52%) had ≥ 2 mut. PIK3CA (42%), TP53 (32%), KRAS (20%), PTEN (16%), and CTNNB1 (16%) were the most common mut seen. PIK3CA mut were seen in 39% of type 1 and 43% of type 2 EC (p = 0.74). PTEN mut were more common in type I EC (p = 0.02); TP53 mut more common in type 2 (p < 0.01). 31 pts (40%) had targeted therapy - 5 genotype-matched. Overall disease control rate (RR + SD at 12 weeks) was 53% with no difference seen with antiangiogenic agents (25 pts; 60%), PI3K/AKT/MTOR agents (7; 57%) or matched therapy (5; 40 % p = 0.64)). Time to progression on targeted therapy was not better than prior systemic therapy (HR 1.5 p = 0.09). 15% stopped due to AEs rather than PD. Of 16 pts offered a phase I trial 50% did not start, often due to ECOG decline. Two exceptional responders were identified: (i) clear cell EC (no mut) with PR for 2.6y on ixabepilone; and (ii) recurrent serous EC (3 mut: PIK3CA, KRAS, APC) with CR on sunitinib for 7.2y. Exome sequencing of the 2nd case found > 2400 somatic coding mut (43 point mut/coding Mb) and few copy-number alterations (possible MSI-hypermutated subtype). Preliminary somatic mut of interest include: 5 in genes significantly mutated in EC; 4 in genes encoding known targets of sunitinib; and 13 in kinase domains of other proteins. Conclusions: Genotype-matched therapy in EC is complicated by genomic heterogeneity, comorbidities, and tolerance of therapy. Future EC trials should develop algorithms for multiple mutations and account for pt comorbidities in design. Clinical trial information: NCT01505400.
Gastrointestinal stromal tumors: A 10-year experience from a tertiary care center in India.
Authors: Nida Iqbal Shapoo, Atul Sharma, N. K. Shukla, BK Mohanti, S. V. S. Deo, Peush Sahni, Sujoy Pal, Sushmita Pathy, Vijay Murugan, Naveed Iqbal
Journal: Journal of Clinical Oncology (2014)

e21509 Background: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Due to a limited published data on GIST from Indian sub-continent, we aimed to study the tumor and treatment characteristics in 109 patients of GIST referred to a tertiary care centre. Methods: Data pertaining to 109 patients of gastrointestinal stromal tumors was retrieved from a database between April 2002-Dec 2012. Results: Median age was 47 years (range 17-70 years). The primary site of involvement was small intestine in 42% , stomach in 28%, large intestine in 12% and anorectum in 5% patients. Mean tumor size was 12 cm (range 2-50 cm). Forty-four (40%) patients were metastatic at presentation, the most common site of metastases being liver in 68% patients. Surgery was performed in 75 (71%) patients,out of whom, 44 (58%) achieved negative surgical margins. Seventy-nine (74%) patients were in high risk category, mainly because of high mitotic index (>5/50hpf). Mutation analysis was not done. Imatinib was given as a primary therapy in 30 (29%) unresectable patients and as an adjuvant therapy in 48 (60%) patients. Responses in patients who received imatinib only; complete response in 2 (7%), partial response in 4(13%), stable disease in 14 (47%) and progressive disease in 6 (20%) patients. Recurrences were seen in 31% patients in non-metastatic group. Five-years EFS and OS were 47% and 65% in non-metastatic group vs 31% and 40% in the metastatic group. Univariate survival analysis found that low risk tumors were associated with better overall survival (p-0.01). In multivariate analysis, none of the factors predicted survival. Conclusions: This is a single center experience of unselected patients. Even though survival is comparable to published reports,the limitation is lack of mutation analysis.
A probabilistic threshold analysis of metformin (Met) with enzalutamide (Enza) to determine the cost and added efficacy needed to make such a combination theray cost-effective (CE).
Authors: Jordan Hill, Peter Venner, Mike Paulden, Christopher McCabe, Scott A. North, Brita Lavender Danielson, Nawaid Usmani
Journal: Journal of Clinical Oncology (2017)

e577 Background: Enza has become known for its' effectiveness in treating patients with metastatic castrate-resistant prostate cancer. However, Enza is expensive (~$3175/month) and unlikely to be CE at any willingness to pay (WTP) threshold from $0-$125 000/quality-adjusted life years (QALYs). Met is inexpensive (~$8.00/month) and recently two large population-based studies of prostate cancer (PCa) demonstrated that diabetics taking Met had improved PCa specific and overall survival compared to those not taking Met. As a result we theorized that there must be a cost of Enza and a specific added effect Met could provide that would make Met a CE adjuvant therapy to Enza even though it is not currently used as such. Methods: We constructed a Markov-based decision analytic model and performed a probabilistic threshold analysis to narrow in on several combinations of costs of Enza and added efficacies needed to make Enza + Met a CE combination therapy at different WTP thresholds. Costs, utilities, and transition probabilities were derived from existing literature. Effectiveness was measured using QALYs. Costs and QALYs were considered over a lifetime horizon and discounted at 5% per annum. Results: At a WTP threshold of $50 000/QALY Enza + Met is unlikely to be CE no matter the cost decrement or added efficacy applied to the model. At a WTP threshold of $75 000/QALY Met is also unlikely to be CE unless the price of Enza could drop to $1934/month and Met could also add 1% to the efficacy of Enza. At Enza's current cost and a WTP threshold of $100 000, Enza + Met could be CE barring Met adds 0.621% to the number of patients still on treatment at 36 months. Conclusions: Enza + Met is unlikely to be CE at WTP thresholds of $50 000/QALY or $75 000/QALY unless there is a significant price drop for Enza; these results make sense because a therapy that is considered not CE at these WTP thresholds by itself is unlikely to be CE with a theoretical adjuvant therapy that would hold a patient on such a treatment for even longer. Our results show that the only way for Enza + Met to be CE is through the theoretical overall survival benefit of Met as the price of Enza is unlikely to drop any time soon.
Radioimmunotherapy (RIT) with 90Y-Ibritumomab Tiuxetan (Zevalin) for the Treatment of Relapsed or Resistant Aggressive Diffuse Large B-Cell Lymphoma (DLBCL) Heavily Pretreated with Rituximab + Chemotherapy: A GIMURELL Experience.
Authors: Barbara Botto, Marilena Bellò, Giulia Benevolo, Maria Giuseppina Cabras, Claudia Castellino, Annalisa Chiappella, Giuseppe Fioritoni, Roberto Freilone, Maurizio Martelli, Lorella Orsucci, Patrizia Pregno, Paola Scapoli, Anna Tonso, Giovanni Bisi, Umberto Vitolo, Eugenio Gallo
Journal: Blood (2007)
Yellow fever in a traveller returning from Suriname to the Netherlands, March 2017
Authors: Marjan Wouthuyzen-Bakker, Marjolein Knoester, Aad P van den Berg, Corine H GeurtsvanKessel, Marion PG Koopmans, Coretta Van Leer-Buter, Bob Oude Velthuis, Suzan D Pas, Wilhelmina LM Ruijs, Jonas Schmidt-Chanasit, Stephen GS Vreden, Tjip S van der Werf, Chantal BEM Reusken, Wouter FW Bierman
Journal: Eurosurveillance (2017)

A Dutch traveller returning from Suriname in early March 2017, presented with fever and severe acute liver injury. Yellow fever was diagnosed by (q)RT-PCR and sequencing. During hospital stay, the patient's condition deteriorated and she developed hepatic encephalopathy requiring transfer to the intensive care. Although yellow fever has not been reported in the last four decades in Suriname, vaccination is recommended by the World Health Organization for visitors to this country.
Prognostic value of metastatic tumoral caveolin-1 expression in patients with resected gastric cancer.
Authors: Der Sheng Sun, Soon Auck Hong, Han Hong Lee, Hye Sung Won, Yoon Ho Ko
Journal: Journal of Clinical Oncology (2017)

83 Background: Caveolin-1 (Cav-1), as the main component of caveolae, has complex roles in tumourigenesis and clinical outcomes in a variety of human malignancies. We investigated Cav-1 in primary and metastatic tumor of gastric cancer (GC) and its association with clinical outcomes. Methods: All specimens evaluated were obtained from 145 patients with GC who had undergone curative gastrectomy. The primary outcomes measured were the expression levels of Cav-1 by immunohistochemistry and its association with clinicopathological parameters and patient survival. Results: Among the 145 patients, the frequency of high expression of stromal Cav-1 within primary tumor and tumoral Cav-1 protein in metastatic lymph node were 22.5% (18/145) and 16.6% (15/91). In the multivariate analysis tumoral Cav-1 protein in metastatic lymph node showed prognostic significance for relapse-free survival (RFS, HR, 3.934; 95% CI, 1.882–8.224; P &lt; 0.001) and cancer-specific survival outcome (CSS, HR, 3.985; 95% CI, 1.620 – 8.623; P = 0.002). In addition, it remained as a strong indicator of poor prognosis for RFS (HR, 3.137; 95% CI, 1.445 – 6.810; P = 0.004) and CSS (HR, 2.509; 95% CI, 1.079 – 5.838; P = 0.033). Conclusions: High expression of tumoral Cav-1 protein in metastatic lymph node shows a strong negative association with the clinical outcomes in patients with curatively resected GC, suggesting that this protein have potential uses as novel prognostic markers.
First-in-human phase I dose-escalation study of the oral selective C-met inhibitor EMD 1204831 in patients with advanced solid tumors.
Authors: Hesham M. Amin, Gerald Steven Falchook, Siqing Fu, David S. Hong, Apostolia Maria Tsimberidou, Aung Naing, Jennifer J. Wheler, Sarina Anne Piha-Paul, Filip Janku, Manfred B Klevesath, Virginie Jego, Andreas Johne, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2012)

3107^ Background: The cell surface receptor tyrosine kinase c-Met and its ligand, the hepatocyte growth factor, are implicated in tumor cell migration, invasion, survival, and proliferation. EMD 1204831 is a novel potent and highly selective reversible, ATP-competitive small molecule c-Met inhibitor. Methods: This is a phase I, first-in-human clinical trial with escalating doses of EMD 1204831 (NCT01110083). The primary objective was to determine the maximum tolerated dose (MTD). Secondary objectives included evaluation of safety, pharmacokinetics (PK), pharmacodynamics (Pd), and preliminary anti-tumor activity. Eligible patients had advanced solid tumors not amenable to standard therapies. Following a classical 3+3 dose-escalation scheme, successive cohorts of patients were treated with twice daily (BID) oral EMD 1204831 in 21-day cycles. Pd markers were evaluated in paired tumor biopsies (phospho-c-Met). Results: Until 31 December 2011, 30 patients were enrolled and treated. The dose was escalated in successive cohorts starting from 50 mg BID up to 1400 mg BID. After first (single) administration, median C max and AUC 0–12 values increased with dose. At higher doses, a decrease in exposure of EMD 1204831 was noted after multiple dosing, potentially caused by autoinduction of the compound’s metabolism. Further dose escalation was discontinued, and no further patients were enrolled. One dose-limiting toxicity (DLT) of grade (G) 3 pancreatitis, considered as a serious adverse event (AE), was observed at 400 mg BID. No other DLTs or treatment-related serious AEs were observed. The remaining treatment-related AEs of G2 or higher included G3 and G2 lipase elevation (n=1 for each grade), G2 upper abdominal pain (n=2), G2 gastroesophageal reflux disease (n=2), and G2 constipation (n=1). Twenty-five patients (83%) had no drug-related toxicity greater than G1. Of 29 patients evaluable for anti-tumor activity, 3 had stable disease lasting for at least 4 months. Conclusions: Due to potential autoinduction of the compound’s metabolism, dose escalation was discontinued before an MTD was reached. Final safety, PK, and clinical tumor response results will be presented.
SWOG S1320: A randomized phase II trial of intermittent versus continuous dosing of dabrafenib and trametinib in BRAF<sup>V600E/k</sup> mutant melanoma.
Authors: Alain Patrick Algazi, Megan Othus, Adil Daud, Janice M. Mehnert, Christopher D. Lao, Ragini Reiney Kudchadkar, Kenneth F. Grossmann, Roger Lo, James Moon, John M. Kirkwood, Antoni Ribas
Journal: Journal of Clinical Oncology (2015)

TPS9093 Background: Combined BRAF and MEK inhibition yields improved response rates and overall survival compared with BRAF inhibitor monotherapy in BRAF mutant melanoma patients(Robert et al., 2015), but the median progression-free survival is less than one year. Recent preclinical data suggest that resistant BRAF mutant melanoma cells adapt to the presence of BRAF inhibitors, but these adaptations may be disadvantageous in the absence of drug(Das Thakur et al., 2013; Moriceau et al., 2015). Further in vitro and in vivo studies suggest that intermittent dosing of BRAF inhibitors and especially BRAF + MEK inhibitor combinations may extend disease control in BRAF mutant melanoma. Based on these findings, S1320, an intergroup SWOG/ECOG randomized phase 2 clinical trial, was designed to determine whether an intermittent dosing schedule of dabrafenib and trametinib improves progression-free survival (PFS) in BRAF mutant melanoma patients treated with a standard, continuous dosing regimen. Methods: ELIGIBILITY: Patients with unresectable or metastatic BRAFV600E/K melanoma who have not been treated previously with BRAF or MEK inhibitors are eligible. Patients must have adequate end organ function and any known brain metastases must be treated prior to enrollment. DESIGN: Patients will be treated with dabrafenib at 150 mg twice daily and trametinib 2 mg twice daily during an 8 week lead in period. Patients without disease progression at the end of the lead in period will be randomized 1:1 to either continuous dosing or intermittent dosing according to a 5 weeks on, 3 weeks off schedule. Reimaging will be performed once every 8 weeks. ENDPOINTS: The primary endpoint of this study is the PFS in the continuous versus intermittent dosing arms. Secondary endpoints include the toxicity, best overall response rate, and overall survival. Early and late molecular events associated with disease progression will also be assessed using serial biopsies in a subset of patients in each arm. Support: NIH/NCI/NCTN grants CA180888, CA180819, CA180820 Clinical trial information: NCT02196181.
Phase 1b of anticancer stem cell antibody OMP-59R5 (anti-Notch2/3) in combination with etoposide and cisplatin (EP) in patients (pts) with untreated extensive-stage small-cell lung cancer (ED-SCLC).
Authors: David R. Spigel, Alexander I. Spira, Robert M. Jotte, Shirish M. Gadgeel, Alain C. Mita, Lowell L. Hart, Ann Kapoun, Lu Xu, Dawn Hill, Lei Zhou, Jakob Dupont, Maria Catherine Pietanza
Journal: Journal of Clinical Oncology (2014)

7601 Background: The Notch pathway plays a central role in embryonic development, the regulation of stem and progenitor cells, and is implicated centrally in many human cancers, including SCLC. OMP-59R5, a fully human IgG2 antibody, inhibits signaling of Notch2 and 3 receptors. Anti-tumor activity was noted in 7 of 8 pt-derived SCLC xenografts expressing Notch 2 and 3 with OMP-59R5 treatment. The maximum tolerated dose (MTD) of single agent OMP-59R5 was 7.5mg/kg IV every 3 weeks (Smith, EORTC 2012); the main dose-limiting toxicity (DLT) was Grade 3 diarrhea. This study is to determine the MTD, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of OMP-59R5 in combination with EP in ED-SCLC. Methods: Cohorts of 3 to 6 pts were treated at each dose level of OMP-59R5. OMP-59R5 was given IV on Day 1 of each 21 day cycle along with etoposide 100 mg/m2 on Days 1, 2, and 3 and cisplatin 80 mg/m2 on Day 1. After 6 cycles, pts continued OMP-59R5 alone every 21 days in the absence of disease progression or unacceptable toxicities. Results: By Jan 17, 2014, 8 pts were treated. No DLTs have occurred. Frequently reported (>25%) adverse events (all grades, G) regardless of relationship were: fatigue(62.5%), nausea(62.5%), anemia(50%), diarrhea(50%), peripheral edema(50%), alopecia(37.5%), blood creatinine increase(37.5%), decreased appetite(37.5%), neutropenia(37.5%), and weight loss(37.5%); Of these, fatigue(50%), anemia(37.5%), diarrhea(37.5%), nausea(37.5%), alopecia(25%), decreased appetite(25%), and weight loss(25%) were considered related to OMP-59R5-treatment. The events were mostly G 1 or 2, and managed with supportive care. Additional data are below (see Table). Conclusions: OMP-59R5 with EP is well tolerated. The MTD has not been reached. Encouraging anti-tumor activity is observed. Updated Safety, PK/PD, and efficacy data will be presented. Clinical trial information: NCT01859741. OMP-59R5 Dose (mg/kg) 5 (n=3) 7.5 (n=3) 10 (n=2) Etoposide (mg/m2) 100 Cisplatin (mg/m2) 80 DLT evaluable 3 3 2 incidence - - - RECIST 1.1 evaluable 3 3 -- Best response PR 3 - 2 SD - 3 - PD - - - mPFS (days) 175 - - Pts still on treatment 1 3 2